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Dietary calcium and blood pressure: a meta-analysis of randomized clinical trials.
Allender PS, Cutler JA, Follmann D, et al.
Ann Intern Med. 1996 May 1; 124(9):825-31.
PURPOSE: To assess the effect of dietary calcium supplementation on blood pressure. DATA SOURCES: Published reports of trials studying the effect of dietary calcium supplementation on blood pressure were identified by a search of previous reviews, a MEDLINE search, a manual review of journal articles, and a review of abstracts from scientific meetings. STUDY SELECTION: Randomized clinical trials in which dietary calcium intake varied by intervention group were selected. Multifactorial trials were not included. DATA SYNTHESIS: Data from 28 active treatment arms or strata from 22 randomized clinical trials were pooled using a weighted average method, with weights proportional to the inverse of the variance of the treatment effect. The total sample comprised 1231 persons. Because trials of both normotensive and hypertensive persons were included, subgroup analyses could be done. Pooled estimates of the effect of calcium supplementation on blood pressure were -0.18 mm Hg for diastolic blood pressure (95% CI, -0.75 to 0.40 mm Hg) and -0.89 mm Hg for systolic blood pressure (CI, -1.74 to -0.05 mm Hg). Pooled estimates for systolic blood pressure were -0.53 mm Hg (CI, -1.56 to 0.49 mm Hg) for trials of normotensive persons and -1.68 mm Hg (CI, -3.18 to -0.18 mm Hg) for trials of hypertensive persons. Diastolic blood pressure was not significantly affected in either subgroup. CONCLUSION: The pooled estimate shows a statistically significant decrease of systolic blood pressure with calcium supplementation, both for hypertensive persons and for the overall sample. However, the effect is too small to support the use of calcium supplementation for preventing or treating hypertension
A clinical trial of the effects of dietary patterns on blood pressure.
Appel LF, DASH Collaborative Research Group.
N Engl J Med. 1997;(336):1117.
none
Diet supplementation with fish oils and blood pressure reduction: a metabolism-analysis.
Appel LF MESAWP.
Ann Intern Med. 1994;120-9.
Does supplementation of diet with 'fish oil' reduce blood pressure? A meta-analysis of controlled clinical trials.
Appel LJ, Miller ER, III, Seidler AJ, et al.
Arch Intern Med. 1993 Jun 28; 153(12):1429-38.
BACKGROUND: Several lines of evidence suggest that supplementation of diet with omega-3 polyunsaturated fatty acids (omega-3 PUFA), commonly referred to as fish oils, may reduce blood pressure (BP). However, most clinical trials of omega-3 PUFA supplementation have been of insufficient size to detect relevant BP changes. METHODS: We conducted a meta-analysis of 17 controlled clinical trials of omega-3 PUFA supplementation. To estimate an overall effect of omega-3 PUFA supplementation on BP, we calculated the net BP change in each trial (BP delta in omega-3 PUFA group minus BP delta in control group), which was then weighted according to the inverse of the variance. RESULTS: In the 11 trials that enrolled normotensive individuals (n = 728), omega-3 PUFA supplementation led to significant reductions of systolic BP (SBP) and diastolic BP (DBP) in two and one trials, respectively. In the six studies that enrolled untreated hypertensives (n = 291), significant reductions of SBP and DBP were present in two and four trials, respectively. Weighted, pooled estimates of SBP and DBP change (mm Hg) with 95% confidence intervals were -1.0 (-2.0 to 0.0) and -0.5 (-1.2 to +0.2) in the trials of normotensives, and -5.5 (-8.1 to -2.9) and -3.5 (-5.0 to -2.1) in the trials of untreated hypertensives. In 13 of 17 studies, trial duration was less than 3 months. Doses of omega-3 PUFA tended to be high (average dose > 3 g/d in 11 trials). The magnitude of BP reduction was greatest at high BP but was not significantly associated with dose of omega-3 PUFA. Side effects, most commonly eructation and a fishy taste, occurred more frequently in omega-3 PUFA participants than in control participants (28% vs 13%, P < .001). CONCLUSIONS: Our analyses indicate that diet supplementation with a relatively high dose of omega-3 PUFA, generally more than 3 g/d, can lead to clinically relevant BP reductions in individuals with untreated hypertension. However, use of omega-3 PUFA as antihypertensive therapy will require demonstration of long-term efficacy and patient acceptability of lower doses
Gamma-linolenic acid dietary supplementation can reverse the aging influence on rat liver microsome delta 6-desaturase activity.
Biagi PL, Bordoni A, Hrelia S, et al.
Biochim Biophys Acta. 1991 May 8; 1083(2):187-92.
We have recently demonstrated that in rats the process of delta 6-desaturation of linoleic and alpha-linolenic acids slows with aging. One method of counteracting the effect of slowed desaturation of linoleic acid would be to provide the 6-desaturated metabolite, gamma-linolenic acid (18:3(n-6) GLA) directly. We have here investigated the 6-desaturation of both linoleic and alpha-linolenic acids in liver microsomes of young and old rats given GLA in the form of evening primrose oil (EPO) (B diet) in comparison to animals given soy bean oil alone (A diet), monitoring also the fatty acid composition of liver microsomes and relating this to the microviscosity of the membranes. In young rats the different experimental diets did not produce any difference in delta 6-desaturase (D6D) activity on either substrate suggesting that, when D6D activity is at or near its peak, the variations in diet tested are unable to influence it. In the old animals the rate of 6-desaturation of linoleic and particularly of alpha-linolenic acid was significantly greater in the B diet fed animals than in the A diet fed. The effects of the diets on the fatty acid composition of liver microsomes were consistent with the findings with regard to 6-desaturation. Administration of GLA partially corrected the abnormalities of n-6 essential fatty acid (EFA) metabolism by raising the concentration of 20:4(n-6) and other 6-desaturated EFAs. Furthermore, the GLA rich diet also increased the levels of dihomo-gamma-linolenic acid and of 6-desaturated n-3 EFAs in the liver microsomes. The microviscosity of microsomal membranes as indicated by DPH polarization was correlated with the unsaturation index of the same membranes. There was a very strong correlation between the two. In both young and old rats the B diet reduced the microviscosity and increased the unsaturation index. However, the effect was much greater in the old animals
Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia.
Boger RH, Bode-Boger SM, Sydow K, et al.
Arterioscler Thromb Vasc Biol. 2000 Jun; 20(6):1557-64.
Hyperhomocyst(e)inemia is associated with endothelial dysfunction. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of endothelium-dependent nitric oxide. We tested the hypothesis that hyperhomocyst(e)inemia is associated with an elevated plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. One group of adult cynomolgus monkeys was fed either a control or hyperhomocyst(e)inemic diet for 4 weeks in a randomized crossover design. The second group was fed an atherogenic diet that produces both hyperhomocyst(e)inemia and hypercholesterolemia for 17 months, followed by an atherogenic diet supplemented with B vitamins for 6 months to decrease plasma homocyst(e)ine concentration. Human endothelial cells were used to study the effects of methionine and homocysteine in the presence or absence of B vitamins or the methylation inhibitor S-adenosylhomocysteine on the formation of ADMA and its inactive stereoisomer, symmetric dimethylarginine. The hyperhomocyst(e)inemic diet produced 2- to 3-fold increases in plasma levels of homocyst(e)ine and ADMA (both P<0.05). The atherogenic diet also produced elevated plasma levels of homocyst(e)ine and ADMA (both P<0. 05). Supplementation of the atherogenic diet with B vitamins decreased the plasma levels of homocyst(e)ine but did not affect the plasma levels of ADMA or endothelial function. There was a strong correlation between plasma ADMA and homocyst(e)ine and a strong inverse correlation between ADMA and carotid artery relaxation to acetylcholine. ADMA release by cultured endothelial cells was significantly increased in the presence of methionine or homocysteine. This effect was blocked by S-adenosylhomocysteine but not by B vitamins. We conclude that plasma levels of ADMA are elevated in hyperhomocyst(e)inemia. Because ADMA acts as a competitive inhibitor of endothelial nitric oxide synthase, these findings suggest a novel mechanism for impaired endothelial function in hyperhomocyst(e)inemia
Evidence for age-related differences in the fatty acid composition of human adipose tissue, independent of diet.
Bolton-Smith C, Woodward M, Tavendale R.
Eur J Clin Nutr. 1997 Sep; 51(9):619-24.
OBJECTIVE: To test the null-hypothesis that no age difference in adipose tissue fatty acid composition exists independent of dietary fat intake. DESIGN: A cross-sectional survey of coronary heart disease risk factors, the Scottish Heart Health Study, provided needle biopsy adipose tissue fatty acid data and food frequency-derived dietary data. SETTING: Twenty-two Scottish Districts between 1984 and 1986. SUBJECTS: A total of 10,359 men and women aged 40-59 y were randomly recruited in sex and five-year age bands from GP lists. A sub-set of 2308 men and 2049 women (42%) provided satisfactory adipose tissue and dietary data. MAIN OUTCOME AND MEASURES: Multiple regression analysis (adjusting for dietary fats, body mass index and smoking, with and without menopause status for women) of the relationship between individual fatty acids in adipose tissue and age, and between age and the ratio of linoleic acid (C18:2, n-6) to gamma-linolenic acid (C18:3, n-6) as an indicator of delta-6 desaturase activity. RESULTS: Sex-consistent changes with age occurred for linoleate (adjusted regression slope +/- s.e. for men -0.299 +/- 0.1339 and for women -0.504 +/- 0.1731) and gamma-linolenate (adjusted regression slope +/- s.e. for men -0.141 +/- 0.0341 and for women -0.154 +/- 0.0469) both P < 0.0001. These changes gave rise to a significant increase (P < or = "0.005)" in the C18:2, n-6 to C18:3, n-6 ratio with age). Dihomo-gamma-linolenic acid (C20:3, n-6) and docosahexa- plus docosapentaenoic acids (C22:5 + C22:6, n-3) also increased significantly with age (P < or = "0.01)." For the latter, the adjusted regression slopes were far greater for women (0.596 +/- 0.0575) than men (0.131 +/- 0.0417). CONCLUSIONS: The results show that ageing does influence adipose tissue fatty acid composition independent of diet. The sex differences may partially be due to inadequate adjustment for changes in sex hormone status in males with ageing. Using the current indicator, a decline in the rate limiting step of beta-6 desaturation appeared to occur with age, and was greater in women than in men. These results may indicate that an increase in dietary gamma-linolenic acid (C18:3, n-6) is necessary with age to offset the relative imbalance between PUFA levels which appears to occur. However, any direct health benefit regarding the common diseases of ageing from such a strategy still remain to be clarified
The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids.
Borkman M, Storlien LH, Pan DA, et al.
N Engl J Med. 1993 Jan 28; 328(4):238-44.
BACKGROUND. Insulin resistance and hyperinsulinemia are features of obesity, non-insulin-dependent diabetes mellitus, and other disorders. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty-acid composition of the phospholipids within the muscle membranes involved in the action of insulin. METHODS. We determined the relation between the fatty-acid composition of skeletal-muscle phospholipids and insulin sensitivity in two groups of subjects. In one study, we obtained samples of the rectus abdominis muscle from 27 patients undergoing coronary artery surgery; fasting serum insulin levels provided an index of insulin sensitivity. In the second study, a biopsy of the vastus lateralis muscle was performed in 13 normal men, and insulin sensitivity was assessed by euglycemic-clamp studies. RESULTS. In the patients undergoing surgery, the fasting serum insulin concentration (a measure of insulin resistance) was negatively correlated with the percentage of individual long-chain polyunsaturated fatty acids in the phospholipid fraction of muscle, particularly arachidonic acid (r = -0.63, P < 0.001); the total percentage of C20-22 polyunsaturated fatty acids (r = "-0.68," P < 0.001); the average degree of fatty-acid unsaturation (r = "-0.61," P < 0.001); and the ratio of the percentage of C20:4 n-6 fatty acids to the percentage of C20:3 n-6 fatty acids (r = "-0.55," P < 0.01), an index of fatty-acid desaturase activity. In the normal men, insulin sensitivity was positively correlated with the percentage of arachidonic acid in muscle (r = "0.76," P < 0.01), the total percentage of C20-22 polyunsaturated fatty acids (r = "0.76," P < 0.01), the average degree of fatty-acid unsaturation (r = "0.62," P < 0.05), and the ratio of C20:4 n-6 to C20:3 n-6 (rho = "0.76," P = "0.007)." CONCLUSIONS. Decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids in skeletal-muscle phospholipids, raising the possibility that changes in the fatty-acid composition of muscles modulate the action of insulin
Hyperhomocysteinemia in stroke-prevalence cause, and relationship to type of stroke and stroke risk factors.
Brattstrom L.
Eur J Clin Invest. 1992;(22):214-21.
The Healing Nutrients Within 1987.
Braverman EPC.
1987;
none
Dietary modulation of endothelial function: implications for cardiovascular disease.
Brown AA, Hu FB.
Am J Clin Nutr. 2001 Apr; 73(4):673-86.
The vascular endothelium is the primary site of dysfunction in many diseases, particularly cardiovascular disease. A variety of risk factors, including smoking, hypercholesterolemia, hyperhomocysteinemia, hypertension, and diabetes mellitus, adversely affect endothelial function. Emerging evidence suggests an important role of dietary factors in modulating endothelial function. In particular, n-3 fatty acids, antioxidant vitamins (especially vitamins E and C), folic acid, and L-arginine appear to have beneficial effects on vascular endothelial function, either by decreasing endothelial activation or by improving endothelium-dependent vasodilation in patients at high risk of cardiovascular disease as well as in healthy subjects. These effects may serve as one potential mechanism through which these nutrients reduce the risk of cardiovascular disease, as observed in epidemiologic studies and several clinical trials. This article reviews clinical and experimental evidence regarding the role of these nutrients in modulating endothelial function and their potential to prevent cardiovascular disease
Activation of L-arginine transport in peripheral blood mononuclear cells in chronic renal failure.
Brunini TM, Roberts NB, Yaqoob MM, et al.
Pflugers Arch. 2002 Oct; 445(1):147-51.
Transport of LL-arginine, the precursor for nitric oxide (NO) synthesis, has been investigated in human peripheral blood mononuclear cells (PBMCs) obtained from healthy volunteers and chronic renal failure patients. Chronic renal failure patients were either on treatment by haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). Saturable influx of L-arginine in PBMCs was mediated by the cationic amino acid transport systems y(+) and y(+)L. Initial rates of L-arginine transport (2 microM) via system y(+) were significantly increased in chronic renal failure patients, whereas transport via system y(+)L was unaffected. The increase in L-arginine transport via system y(+) was: 1.7-fold in uraemic patients on CAPD, 4.3-fold in uraemic patients pre-haemodialysis and 2.6-fold post-haemodialysis. When the intracellular PBMCs amino acid profile was analysed in chronic renal failure patients and control subjects, L-lysine and L-arginine concentrations were significantly increased in pre-haemodialysis uraemic patients and restored to normal values by haemodialysis and CAPD. The present study provides the first evidence that system y(+) mediates the increased transport of L-arginine in PBMCs from patients with chronic renal failure. The increased activity of system y(+) may provide the necessary supply of L-arginine to sustain NO synthesis in PBMCs exposed to increased levels of circulating cytokines in chronic renal failure
N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials.
Bucher HC, Hengstler P, Schindler C, et al.
Am J Med. 2002 Mar; 112(4):298-304.
PURPOSE: Observational studies have shown an inconsistent association between n-3 polyunsaturated fatty acids and the risk of coronary heart disease. We investigated the effects of dietary and non-dietary (supplemental) intake of n-3 polyunsaturated fatty acids on coronary heart disease. SUBJECTS AND METHODS: We searched the literature to identify randomized controlled trials that compared dietary or non-dietary intake of n-3 polyunsaturated fatty acids with a control diet or placebo in patients with coronary heart disease. Studies had to have at least 6 months of follow-up data, and to have reported clinical endpoint data. We identified 11 trials, published between 1966 and 1999, which included 7951 patients in the intervention and 7855 patients in the control groups. RESULTS: The risk ratio of nonfatal myocardial infarction in patients who were on n-3 polyunsaturated fatty acid-enriched diets compared with control diets or placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.2, P = 0.16; Breslow-Day test for heterogeneity, P = 0.01), and the risk ratio of fatal myocardial infarction was 0.7 (95% CI: 0.6 to 0.8, P 0.20). In 5 trials, sudden death was associated with a risk ratio of 0.7 (95% CI: 0.6 to 0.9, P 0.20), whereas the risk ratio of overall mortality was 0.8 (95% CI: 0.7 to 0.9, P 0.20). There was no difference in summary estimates between dietary and non-dietary interventions of n-3 polyunsaturated fatty acids for all endpoints. CONCLUSION: This meta-analysis suggests that dietary and non-dietary intake of n-3 polyunsaturated fatty acids reduces overall mortality, mortality due to myocardial infarction, and sudden death in patients with coronary heart disease
Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension.
Burke BE, Neuenschwander R, Olson RD.
South Med J. 2001 Nov; 94(11):1112-7.
BACKGROUND: Increasing numbers of the adult population are using alternative or complementary health resources in the treatment of chronic medical conditions. Systemic hypertension affects more than 50 million adults and is one of the most common risk factors for cardiovascular morbidity and mortality. This study evaluates the antihypertensive effectiveness of oral coenzyme Q10 (CoQ), an over-the-counter nutritional supplement, in a cohort of 46 men and 37 women with isolated systolic hypertension. METHODS: We conducted a 12-week randomized, double-blind, placebo-controlled trial with twice daily administration of 60 mg of oral CoQ and determination of plasma CoQ levels before and after the 12 weeks of treatment. RESULTS: The mean reduction in systolic blood pressure of the CoQ-treated group was 17.8 +/- 7.3 mm Hg (mean +/- SEM). None of the patients exhibited orthostatic blood pressure changes. CONCLUSIONS: Our results suggest CoQ may be safely offered to hypertensive patients as an alternative treatment option
Hypertension.
Calvert J.
Clinics in Family Practice. 2001;(3):733-56.
none
Effect of L-arginine on systemic and renal haemodynamics in salt-sensitive patients with essential hypertension.
Campese VM, Amar M, Anjali C, et al.
J Hum Hypertens. 1997 Aug; 11(8):527-32.
In response to a high sodium (Na+) intake, salt-sensitive patients with hypertension retain more Na+ and manifest a greater rise in arterial pressure than salt-resistant patients. Because there is limited information regarding the role of nitric oxide (NO) in salt-sensitivity we examined the effects of L-arginine (500 mg/kg, i.v. for 30 min) on mean arterial pressure and renal haemodynamics in 21 hypertensive and five normotensive African-Americans. At the end of L-arginine infusion mean arterial pressure fell more in salt-sensitive (-11.5 +/- 2.5) than in salt-resistant (-3.7 +/- 1.5 mm Hg) and control subjects (-3.2 +/- 3.8 mm Hg). At the end of L-arginine infusion effective renal plasma flow (ERPF) increased more (P < 0.05) in controls (+108 +/- 13.9 ml/min/1.73 m2) than in salt-resistant (+55 +/- 16.0 ml/min/1.73 m2) and salt-sensitive patients (+22 +/- 21.5 ml/min/1.73 m2). This study has shown that salt-sensitive African-Americans manifest different systemic and renal haemodynamic responses to L-arginine than salt-resistant patients and controls. The fall in mean blood pressure following L-arginine was greater in salt-sensitive than in salt-resistant patients and controls, whereas the increase in ERPF was reduced in salt-sensitive compared to salt-resistant and normal subjects. The data are in keeping with the notion that a defect in NO production may participate to the genesis of blood pressure sensitivity to salt
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.
Chobanian AV, Bakris GL, Black HR, et al.
JAMA. 2003 May 21; 289(19):2560-72.
"The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount
Resting venous plasma adrenalin in 70-year-old men correlated positively to survival in a population study: the significance of the physical working capacity.
Christensen NJ, Schultz-Larsen K.
J Intern Med. 1994 Mar; 235(3):229-32.
OBJECTIVE. The aim of the study was to evaluate plasma noradrenaline (NA) and plasma adrenalin (A) as predictors of mortality in a population study. SUBJECTS. All subjects were 70 years of age in 1984. They were selected from the National Person Register. Altogether, 804 subjects participated in a comprehensive medical examination. INTERVENTIONS. Plasma NA and A were measured in blood samples collected after the subjects had rested in the supine position for 15 min. The subjects have now been followed for 7 years. MAIN OUTCOME MEASURES. Seven years later, 115 men and 63 women had died. RESULTS. Cox regression analysis showed that the mortality in the male group was positively correlated to plasma NA (P < 0.002) and inversely correlated to forced vital capacity (P < 0.0000) and plasma A (P < 0.02). A positive correlation was obtained between physical working capacity and plasma A. When an index of physical working capacity was included in the Cox regression analysis, both plasma NA and plasma A became insignificant, whereas a strong positive correlation appeared between physical working capacity and survival (P < 0.0000). Those who had low plasma A values in 1984 tended to die from cardiovascular diseases in the follow-up period, whereas in those who died from cancer, plasma A values were similar to those of the general population. CONCLUSIONS. Subjects with high plasma A values had the best survival rate during the 7 year follow-up period, probably because they also had the best physical working capacity. High plasma NA values, as expected, were associated with a reduced survival rate. Measurements of physical working capacity may be an inexpensive measure of probable survival in 70-year-old subjects
Hyperhomocysteinemia: an independent risk factor for vascular disease.
Clarke R, Daly L, Robinson K, et al.
N Engl J Med. 1991 Apr 25; 324(17):1149-55.
BACKGROUND. Hyperhomocysteinemia arising from impaired methionine metabolism, probably usually due to a deficiency of cystathionine beta-synthase, is associated with premature cerebral, peripheral, and possibly coronary vascular disease. Both the strength of this association and its independence of other risk factors for cardiovascular disease are uncertain. We studied the extent to which the association could be explained by heterozygous cystathionine beta-synthase deficiency. METHODS. We first established a diagnostic criterion for hyperhomocysteinemia by comparing peak serum levels of homocysteine after a standard methionine-loading test in 25 obligate heterozygotes with respect to cystathionine beta-synthase deficiency (whose children were known to be homozygous for homocystinuria due to this enzyme defect) with the levels in 27 unrelated age- and sex-matched normal subjects. A level of 24.0 mumol per liter or more was 92 percent sensitive and 100 percent specific in distinguishing the two groups. The peak serum homocysteine levels in these normal subjects were then compared with those in 123 patients whose vascular disease had been diagnosed before they were 55 years of age. RESULTS. Hyperhomocysteinemia was detected in 16 of 38 patients with cerebrovascular disease (42 percent), 7 of 25 with peripheral vascular disease (28 percent), and 18 of 60 with coronary vascular disease (30 percent), but in none of the 27 normal subjects. After adjustment for the effects of conventional risk factors, the lower 95 percent confidence limit for the odds ratio for vascular disease among the patients with hyperhomocysteinemia, as compared with the normal subjects, was 3.2. The geometric-mean peak serum homocysteine level was 1.33 times higher in the patients with vascular disease than in the normal subjects (P = 0.002). The presence of cystathionine beta-synthase deficiency was confirmed in 18 of 23 patients with vascular disease who had hyperhomocysteinemia. CONCLUSIONS. Hyperhomocysteinemia is an independent risk factor for vascular disease, including coronary disease, and in most instances is probably due to cystathionine beta-synthase deficiency
The endothelium: a new target for therapy.
Cooke JP.
Vasc Med. 2000; 5(1):49-53.
At one time considered merely a monolayer of cells lining the vascular conduit, the endothelium has emerged recently as an organ with functions as complex as any in the body. A highly active regulatory organ, the endothelium senses and assesses the hemodynamic, humoral, and inflammatory signals to which it is constantly exposed by the blood and responds by secreting factors that affect vessel tone and structure. These interactions are not merely of academic interest. It has been increasingly recognized that endothelial dysfunction plays a pivotal role in the development and progression of atherosclerosis and coronary artery disease
Prevention and Treatment of Hypertension Study (PATHS): effects of an alcohol treatment program on blood pressure.
Cushman WC, Cutler JA, Hanna E, et al.
Arch Intern Med. 1998 Jun 8; 158(11):1197-207.
OBJECTIVE: To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure, and whether reduction of alcohol intake can be maintained for 2 years. DESIGN: A randomized controlled trial. METHODS: Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months. The goal of the intervention was the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg, or 80 to 99 mm Hg if recently taking medication for hypertension. RESULTS: Reduction in average weekly self-reported alcohol intake was significantly greater (P<.001) at every assessment from 3 to 24 months in the intervention group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months, with similar reductions after 24 months. The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group (for each, P = ".17" and P = ".18)" for the 6-month primary end point; for the hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = ".58" and P = ".44)." CONCLUSIONS: The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure. The results from the Prevention and Treatment of Hypertension Study (PATHS) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension
Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain.
de Urquiza AM, Liu S, Sjoberg M, et al.
Science. 2000 Dec 15; 290(5499):2140-4.
The retinoid X receptor (RXR) is a nuclear receptor that functions as a ligand-activated transcription factor. Little is known about the ligands that activate RXR in vivo. Here, we identified a factor in brain tissue from adult mice that activates RXR in cell-based assays. Purification and analysis of the factor by mass spectrometry revealed that it is docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid that is highly enriched in the adult mammalian brain. Previous work has shown that DHA is essential for brain maturation, and deficiency of DHA in both rodents and humans leads to impaired spatial learning and other abnormalities. These data suggest that DHA may influence neural function through activation of an RXR signaling pathway
Mechanism of action of coenzyme Q10 in essential hypertension.
Digiesi V.
Curr Ther Res. 1992;(51):668-72.
none
Effect of coenzyme Q10 on essential arterial hypertension.
Digiesi V CFBB.
Curr Ther Res. 1990;(47):841-5.
none
Treatment of hypertension with ascorbic acid.
Duffy SJ, Gokce N, Holbrook M, et al.
Lancet. 1999 Dec 11; 354(9195):2048-9.
In a randomised, double-blind, placebo-controlled study we showed that treatment of hypertensive patients with ascorbic acid lowers blood pressure. Further studies of ascorbic acid to treat hypertension, with clinical endpoints, are warranted
Dietary gamma-linolenic acid lowers blood pressure and alters aortic reactivity and cholesterol metabolism in hypertension.
Engler MM, Engler MB, Erickson SK, et al.
J Hypertens. 1992 Oct; 10(10):1197-204.
OBJECTIVE: To determine the effects of dietary gamma-linolenic acid upon blood pressure, aortic reactivity and cholesterol metabolism in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. DESIGN: Randomized parallel-group study. METHODS: SHR and WKY rats were fed a purified diet containing either sesame or borage oil rich in gamma-linolenic acid for 7 weeks. Blood pressure measured by the tail-cuff method and weight were monitored weekly. At the end of the study, intra-arterial pressor responses to norepinephrine and angiotensin II, and reactivity of isolated aortic rings to norepinephrine, angiotensin II, KCl and acetylcholine were determined. Serum cholesterol and triglycerides were measured. Hepatic and intestinal enzymes and receptors of cholesterol metabolism were also measured. RESULTS: Dietary borage oil significantly decreased blood pressure in SHR and WKY rats compared with sesame oil-fed rats. Pressor responses to norepinephrine and angiotensin II, and aortic reactivity to norepinephrine, angiotensin II, KCl and acetylcholine were not significantly different. The borage oil diet increased serum cholesterol levels in WKY rats and hepatic B-hydroxy-3-methylglutaryl coenzyme A reductase in SHR. CONCLUSION: These data indicate that dietary borage oil has a blood pressure lowering effect in hypertensive and normotensive rats. However, the effect cannot be explained by altered sensitivity to humoral and neural vasoconstrictors or changes in cholesterol metabolism. Other mechanisms should be investigated
Comparative study of diets enriched with evening primrose, black currant, borage or fungal oils on blood pressure and pressor responses in spontaneously hypertensive rats.
Engler MM.
Prostaglandins Leukot Essent Fatty Acids. 1993 Oct; 49(4):809-14.
The effects of oils enriched with gamma-linolenic acid (GLA) on blood pressure and pressor responses were examined in spontaneously hypertensive rats (SHR). Rats were fed purified diets containing evening primrose (EPO), black currant (BCO), borage (BOR) or fungal (FGO) oils for 7 weeks. Significant reductions in blood pressure were obtained in SHR rats maintained on diets enriched with GLA oils. The antihypertensive effect was not associated with enhanced pressor responsiveness to norepinephrine or angiotensin II. Moreover, no differences were found in blood pressure responses to the calcium channel blocker, verapamil. The results suggest that GLA-enriched oils inhibit the development of hypertension in the SHR rat. The blood pressure lowering effect is not mediated by altered pressor responses to vasoconstrictor hormones or intracellular calcium mechanisms
Effects of dietary gamma-linolenic acid on blood pressure and adrenal angiotensin receptors in hypertensive rats.
Engler MM, Schambelan M, Engler MB, et al.
Proc Soc Exp Biol Med. 1998 Jul; 218(3):234-7.
In a previous study, we showed that dietary gamma-linolenic acid (GLA), an omega-6 polyunsaturated fatty acid found in borage oil (BOR), attenuates the development of hypertension in young spontaneously hypertensive rats (SHR). The purpose of this study was to determine the effects of dietary GLA on established hypertension in adult rats, as well as its effects on components of the renin-angiotensin-aldosterone axis. For 5 weeks, male SHR (14-15 weeks old) were fed a basal fat-free diet to which 11% by weight of sesame oil (SES) or BOR was added. Systolic blood pressure (SBP), determined by the tail cuff method, and weight were measured weekly. Plasma renin activity (PRA), aldosterone (PA), and corticosterone (PC) levels were measured at the end of the dietary treatments. The adrenal glands were homogenized, and angiotensin II (ANG II) binding was measured and plotted according to Scatchard. Systolic blood pressure was 12 mmHg lower at Week 5 in SHR fed the BOR diet compared to SES-fed rats (P < 0.005). Weight gains were similar in both dietary groups. Plasma aldosterone was lower, PRA was higher, and the PA/PRA ratio was significantly lower (P < 0.05) in BOR-fed rats. Levels of PC were the same in both groups. The BOR-enriched diet reduced adrenal ANG II receptor density and affinity compared to the SES diet. Results suggest that BOR inhibits adrenal responsiveness to ANG II by an action on adrenal receptors. Our findings demonstrated that dietary GLA lowers SBP in adult SHR. This effect may be mediated, at least in part, by interference with the renin-angiotensin-aldosterone system at the level of adrenal ANG II receptors
Docosahexaenoic acid is an antihypertensive nutrient that affects aldosterone production in SHR.
Engler MM, Engler MB, Goodfriend TL, et al.
Proc Soc Exp Biol Med. 1999 May; 221(1):32-8.
The effects of dietary docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, on blood pressure and some pressure-regulating systems were measured in young spontaneously hypertensive rats (SHR). Plasma aldosterone and corticosterone levels, adrenal aldosterone production in vitro, and characteristics of adrenal angiotensin receptors were measured after 6 weeks of diet. Renal cytochrome P450 (CYP) 4A gene expression and arachidonic acid metabolism by renal microsomes were also investigated. Plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured. Diets contained either corn/soybean oil alone (CSO), or oil enriched with DHA. After 6 weeks, rats fed DHA had systolic blood pressures averaging 34 mmHg less than controls (P < 0.001). Plasma aldosterone levels were 33% lower in the DHA-fed animals than in controls (22 +/- 3 vs. 33 +/- 3.7 ng/dl, P < 0.05). Plasma levels of corticosterone were 18% lower in animals fed DHA than in controls, but this difference was not statistically significant. Adrenal glomerulosa cells from DHA-fed rats produced less aldosterone in vitro in response to angiotensin II, ACTH, or potassium. The difference was less marked when aldosterone production was stimulated by supplying exogenous corticosterone, suggesting an effect of DHA on postreceptor steps in signal transduction or the early pathway of aldosteronogenesis. We found no significant differences in angiotensin receptor subtype, number, or affinity. Production of arachidonic epoxides by renal microsomes was 17% lower in DHA-fed animals than in controls (P < 0.05). Renal cortical mRNA levels of CYP4A genes and formation of 19- and 20-hydroxyeicosatetraenoic acid (HETE) did not differ between dietary groups. Plasma total cholesterol and high-density-lipoprotein (HDL) levels were significantly reduced in SHR fed the DHA supplement, but triglyceride levels were not significantly different. The effects of DHA on steroid and eicosanoid metabolism may be part of the mechanism by which this fatty acid prevents some of the hypertension in growing SHR
Vitamin C intake and mortality among a sample of the United States population.
Enstrom JE, Kanim LE, Klein MA.
Epidemiology. 1992 May; 3(3):194-202.
We examined the relation between vitamin C intake and mortality in the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study cohort. This cohort is based on a representative sample of 11,348 noninstitutionalized U.S. adults age 25-74 years who were nutritionally examined during 1971-1974 and followed up for mortality (1,809 deaths) through 1984, a median of 10 years. An index of vitamin C intake has been formed from detailed dietary measurements and use of vitamin supplements. The relation of the standardized mortality ratio (SMR) for all causes of death to increasing vitamin C intake is strongly inverse for males and weakly inverse for females. Among those with the highest vitamin C intake, males have an SMR (95% confidence interval) of 0.65 (0.52-0.80) for all causes, 0.78 (0.50-1.17) for all cancers, and 0.58 (0.41-0.78) for all cardiovascular diseases; females have an SMR of 0.90 (0.74-1.09) for all causes, 0.86 (0.55-1.27) for all cancers, and 0.75 (0.55-0.99) for all cardiovascular diseases. Comparisons are made relative to all U.S. whites, for whom the SMR is defined to be 1.00. There is no clear relation for individual cancer sites, except possibly an inverse relation for esophagus and stomach cancer among males. The relation with all causes of death among males remains after adjustment for age, sex, and 10 potentially confounding variables (including cigarette smoking, education, race, and disease history)
Predictors and mediators of successful long-term withdrawal from antihypertensive medications. TONE Cooperative Research Group. Trial of Nonpharmacologic Interventions in the Elderly.
Espeland MA, Whelton PK, Kostis JB, et al.
Arch Fam Med. 1999 May; 8(3):228-36.
BACKGROUND: National guidelines recommend consideration of step down or withdrawal of medication in patients with well-controlled hypertension, but knowledge of factors that predict or mediate success in achieving this goal is limited. OBJECTIVE: To identify patient characteristics associated with success in controlling blood pressure (BP) after withdrawal of antihypertensive medication. DESIGN: The Trial of Nonpharmacologic Interventions in the Elderly tested whether lifestyle interventions designed to promote weight loss or a reduced intake of sodium, alone or in combination, provided satisfactory BP control among elderly patients (aged 60-80 years) with hypertension after withdrawal from antihypertensive drug therapy. Participants were observed for 15 to 36 months after attempted drug withdrawal. MAIN OUTCOME MEASURES: Trial end points were defined by (1) a sustained BP of 150/90 mm Hg or higher, (2) a clinical cardiovascular event, or (3) a decision by participants or their personal physicians to resume BP medication. RESULTS: Proportional hazards regression analyses indicated that the hazard (+/- SE) of experiencing an end point among persons assigned to active interventions was 75% +/- 9% (weight loss), 68% +/- 7% (sodium reduction), and 55% +/- 7% (combined weight loss/sodium reduction) that of the hazard for those assigned to usual care. Lower baseline systolic BP (P < .001), fewer years since diagnosis of hypertension (P < .001), fewer years of antihypertensive treatment (P < .001), and no history of cardiovascular disease (P = ".01)" were important predictors of maintaining successful nonpharmacological BP control throughout follow-up, based on logistic regression analysis. Age, ethnicity, baseline level of physical activity baseline weight, medication class, smoking status, and alcohol intake were not statistically significant predictors. During follow-up, the extent of weight loss (P = ".001)" and urinary sodium excretion (P = ".04)" were associated with a reduction in the risk of trial end points in a graded fashion. CONCLUSIONS: Withdrawal from antihypertensive medication is most likely to be successful in patients with well-controlled hypertension who have been recently (within 5 years) diagnosed or treated, and who adhere to life-style interventions involving weight loss and sodium reduction. More than 80% of these patients may have success in medication withdrawal for longer than 1 year
Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology.
Fardella CE, Mosso L, Gomez-Sanchez C, et al.
J Clin Endocrinol Metab. 2000 May; 85(5):1863-7.
There is evidence that primary aldosteronism (PA) may be common in patients with essential hypertension (EH) when determinations of serum aldosterone (SA), plasma renin activity (PRA), and the SA/PRA ratio are used as screening. An inherited form of primary hyperaldosteronism is the glucocorticoid-remediable aldosteronism (GRA) caused by an unequal crossing over between the CYP11B1 and CYP11B2 genes that results in a chimeric gene, which has aldosterone synthase activity regulated by ACTH. The aim of this study was to evaluate the prevalence of PA and the GRA in 305 EH patients and 205 normotensive controls. We measured SA (1-16 ng/dL) and PRA (1-2.5 ng/mL x h) and calculated the SA/PRA ratio in all patients. A SA/PRA ratio level greater than 25 was defined as being elevated. PA was diagnosed in the presence of high SA levels (>16 ng/dL), low PRA levels (50). Probable PA was diagnosed when the SA/PRA ratio was more than 25 but the other criteria were not present. A Fludrocortisone test was done to confirm the diagnosis. GRA was differentiated from other forms of PA by: the aldosterone suppression test with dexamethasone, the high levels of 18-hydroxycortisol, and the genetic detection of the chimeric gene. In EH patients, 29 of 305 (9.5%) had PA, 13 of 29 met all the criteria for PA, and 16 of 29 were initially diagnosed as having a probable PA and confirmed by the fludrocortisone test. Plasma potassium was normal in all patients. The dexamethasone suppression test was positive for GRA in 10 of 29 and 18-hydroxycortisol levels were high in 2 of 29 patients who had also a chimeric gene. In normotensive subjects, 3 of 205 (1.46%) had PA, and 1 of 205 had a GRA. In summary, we found a high frequency of normokalemic PA in EH patients. A high proportion of PA suppressed SA with dexamethasone, but only a few had a chimeric gene or high levels of 18-hydroxycortisol. These results emphasize the need to further investigate EH patients
Plasma testosterone in isolated systolic hypertension.
Fogari R MEPP.
2003.Sep.5:42.
none
Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta.
Forman BM, Chen J, Evans RM.
Proc Natl Acad Sci U S A. 1997 Apr 29; 94(9):4312-7.
Fatty acids (FAs) and their derivatives are essential cellular metabolites whose concentrations must be closely regulated. This implies that regulatory circuits exist which can sense changes in FA levels. Indeed, the peroxisome proliferator-activated receptor alpha (PPARalpha) regulates lipid homeostasis and is transcriptionally activated by a variety of lipid-like compounds. It remains unclear as to how these structurally diverse compounds can activate a single receptor. We have developed a novel conformation-based assay that screens activators for their ability to bind to PPARalpha/delta and induce DNA binding. We show here that specific FAs, eicosanoids, and hypolipidemic drugs are ligands for PPARalpha or PPARdelta. Because altered FA levels are associated with obesity, atherosclerosis, hypertension, and diabetes, PPARs may serve as molecular sensors that are central to the development and treatment of these metabolic disorders
Aspirin use and all-cause mortality among patients being evaluated for known or suspected coronary artery disease: A propensity analysis.
Gum PA, Thamilarasan M, Watanabe J, et al.
JAMA. 2001 Sep 12; 286(10):1187-94.
CONTEXT: Although aspirin has been shown to reduce cardiovascular morbidity and short-term mortality following acute myocardial infarction, the association between its use and long-term all-cause mortality has not been well defined. OBJECTIVES: To determine whether aspirin is associated with a mortality benefit in stable patients with known or suspected coronary disease and to identify patient characteristics that predict the maximum absolute mortality benefit from aspirin. DESIGN AND SETTING: Prospective, nonrandomized, observational cohort study conducted between 1990 and 1998 at an academic medical institution, with a median follow-up of 3.1 years. PATIENTS: Of 6174 consecutive adults undergoing stress echocardiography for evaluation of known or suspected coronary disease, 2310 (37%) were taking aspirin. Patients with significant valvular disease or documented contraindication to aspirin use, including peptic ulcer disease, renal insufficiency, and use of nonsteroidal anti-inflammatory drugs, were excluded. MAIN OUTCOME MEASURE: All-cause mortality according to aspirin use. RESULTS: During 3.1 years of follow-up, 276 patients (4.5%) died. In a simple univariable analysis, there was no association between aspirin use and mortality (4.5% vs 4.5%). However, after adjustment for age, sex, standard cardiovascular risk factors, use of other medications, coronary disease history, ejection fraction, exercise capacity, heart rate recovery, and echocardiographic ischemia, aspirin use was associated with reduced mortality (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.51-0.87; P =.002). In further analysis using matching by propensity score, 1351 patients who were taking aspirin were at lower risk for death than 1351 patients not using aspirin (4% vs 8%, respectively; HR, 0.53; 95% CI, 0.38-0.74; P =.002). After adjusting for the propensity for using aspirin, as well as other possible confounders and interactions, aspirin use remained associated with a lower risk for death (adjusted HR, 0.56; 95% CI, 0.40-0.78; P<.001). The patient characteristics associated with the most aspirin-related reductions in mortality were older age, known coronary artery disease, and impaired exercise capacity. CONCLUSION: Aspirin use among patients undergoing stress echocardiography was independently associated with reduced long-term all-cause mortality, particularly among older patients, those with known coronary artery disease, and those with impaired exercise capacity
Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study.
Hak AE, Witteman JC, de Jong FH, et al.
J Clin Endocrinol Metab. 2002 Aug; 87(8):3632-9.
In both men and women, circulating androgen levels decline with advancing age. Until now, results of several small studies on the relationship between endogenous androgen levels and atherosclerosis have been inconsistent. In the population-based Rotterdam Study, we investigated the association of levels of dehydroepiandrosterone sulfate (DHEAS) and total and bioavailable testosterone with aortic atherosclerosis among 1,032 nonsmoking men and women aged 55 yr and over. Aortic atherosclerosis was assessed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. Relative to men with levels of total and bioavailable testosterone in the lowest tertile, men with levels of these hormones in the highest tertile had age-adjusted relative risks of 0.4 [95% confidence interval (CI), 0.2-0.9] and 0.2 (CI, 0.1-0.7), respectively, for the presence of severe aortic atherosclerosis. The corresponding relative risks for women were 3.7 (CI, 1.2-11.6) and 2.3 (CI, 0.7-7.8). Additional adjustment for cardiovascular disease risk factors did not materially affect the results in men, whereas in women the associations diluted. Men with levels of total and bioavailable testosterone in subsequent tertiles were also protected against progression of aortic atherosclerosis measured after 6.5 yr (SD +/- 0.5 yr) of follow-up (P for trend = 0.02). No clear association between levels of DHEAS and presence of severe aortic atherosclerosis was found, either in men or in women. In men, a protective effect of higher levels of DHEAS against progression of aortic atherosclerosis was suggested, but the corresponding test for trend did not reach statistical significance. In conclusion, we found an independent inverse association between levels of testosterone and aortic atherosclerosis in men. In women, positive associations between levels of testosterone and aortic atherosclerosis were largely due to adverse cardiovascular disease risk factors
The effect of docosahexaenoic acid on aggression in young adults. A placebo-controlled double-blind study.
Hamazaki T, Sawazaki S, Itomura M, et al.
J Clin Invest. 1996 Feb 15; 97(4):1129-33.
41 students took either docosahexaenoic acid (DHA)-rich oil capsules containing 1.5-1.8 grams DHA/day (17 females and 5 males) or control oil capsules containing 97% soybean oil plus 3% fish oil (12 females and 7 males) for 3 mo in a double-blind fashion. They took a psychological test (P-F Study) and Stroop and dementia-detecting tests at the start and end of the study. The present study started at the end of summer vacation and ended in the middle of mental stress such as final exams. In the control group extraggression (aggression against others) in P-F Study was significantly increased at the end of the study as compared with that measured at the start (delta = +8.9%, P = 0.0022), whereas it was not significantly changed in the DHA group (delta = -1.0%). The 95% CI of differences between the DHA and control groups were -16.8 to -3.0%. DHA supplementation did not affect the Stroop and dementia-detecting tests. Thus, DHA intake prevented extraggression from increasing at times of mental stress. This finding might help understand how fish oils prevent disease like coronary heart disease
Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation.
Hambrecht R, Hilbrich L, Erbs S, et al.
J Am Coll Cardiol. 2000 Mar 1; 35(3):706-13.
OBJECTIVES: The aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium-dependent vasodilation in patients with chronic heart failure (CHF). BACKGROUND: Endothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg. and regular physical exercise. METHODS: Forty patients with severe CHF (left ventricular ejection fraction 19 +/- 9%) were randomized to an L-arg. group (8 g/day), a training group (T) with daily handgrip training, L-arg. and T (L-arg. + T) or an inactive control group (C). The mean internal radial artery diameter was determined at the beginning and after four weeks in response to brachial arterial administration of acetylcholine (ACh) (7.5, 15, 30 microg/min) and nitroglycerin (0.2 mg/min) with a transcutaneous high-resolution 10 MHz A-mode echo tracking system coupled with a Doppler device. The power of the study to detect clinically significant differences in endothelium-dependent vasodilation was 96.6%. RESULTS: At the beginning, the mean endothelium-dependent vasodilation in response to ACh, 30 microg/min was 2.54 +/- 0.09% (p = NS between groups). After four weeks, internal radial artery diameter increased by 8.8 +/- 0.9% after ACh 30 microg/min in L-arg. (p < 0.001 vs. C), by 8.6 +/- 0.9% in T (p < 0.001 vs. C) and by 12.0 +/- 0.3% in L-arg. +/- T (p < 0.005 vs. C, L-arg. and T). Endothelium-independent vasodilation as assessed by infusion of nitroglycerin was similar in all groups at the beginning and at the end of the study. CONCLUSIONS: Dietary supplementation of L-arg. as well as regular physical exercise improved agonist-mediated, endothelium-dependent vasodilation to a similar extent. Both interventions together seem to produce additive effects with respect to endothelium-dependent vasodilation
An overview of the 4 randomized trials of aspirin therapy in the primary prevention of vascular disease.
Hebert PR, Hennekens CH.
Arch Intern Med. 2000 Nov 13; 160(20):3123-7.
BACKGROUND: In the primary prevention of cardiovascular disease, in contrast to the recommendations of the American College of Chest Physicians and the American Heart Association, the US Food and Drug Administration recently stated that there was insufficient evidence to judge whether aspirin therapy decreases the risk of a first myocardial infarction. OBJECTIVE: To perform an overview of the 4 primary prevention trials of aspirin therapy to obtain the most reliable estimates of the effects of aspirin therapy on various vascular disease end points. METHODS AND RESULTS: These 4 trials included more than 51,000 subjects and 2284 important vascular events. Those assigned to aspirin therapy experienced significant reductions of 32% (95% confidence interval [CI], 21%-41%) for nonfatal myocardial infarction and 13% (95% CI, 5%-19%) for any important vascular event. There were possible small but nonsignificant increases in risks of vascular disease-related death (1%; 95% CI, -12% to 16%) and nonfatal stroke (8%; 95% CI, -12% to 33%). When strokes were subdivided by type, there was no significant effect of aspirin therapy on the risk of ischemic stroke, but, while based on small numbers, there was a 1.7-fold apparent increase (95% CI, 6%-269%) in the risk of hemorrhagic stroke, which did achieve statistical significance. CONCLUSIONS: For the primary prevention of vascular disease, aspirin therapy confers significant beneficial effects on first myocardial infarction and, as a result, on any important vascular event; these effects are clinically important. Whether there is any reduction in vascular disease-related death or stroke associated with treatment remains unclear because of inadequate numbers of events in the primary prevention trials completed to date. More data on hemorrhagic stroke are also needed. In addition, randomized trial data, especially in women but also in men, are needed to help to formulate a rational public health policy for individuals at usual risk. Meanwhile, these data provide evidence for a significant benefit of aspirin therapy in the primary prevention of myocardial infarction
Loss of delta-6-desaturase activity as a key factor in aging.
Horrobin DF.
Med Hypotheses. 1981 Sep; 7(9):1211-20.
Aging is characterized by a wide variety of defects, particularly in the cardiovascular and immune systems. Cyclic AMP levels fall, especially in lymphocytes. Delta-6-desaturase (D6D) levels have been found to fall rapidly in the testes and more slowly in the liver in aging rats. D6D is an enzyme which converts cis-linoleic acid to gamma-linolenic acid (GLA). Other factors which inhibit D6D activity are diabetes, alcohol and radiation, all of which may be associated with accelerated aging. In meat eaters or omnivores which can acquire arachidonic acid from food, the main consequences of D6D loss will be deficiencies of GLA, dihomogamma-linolenic acid (DGLA) and prostaglandin (PG) E1. PGE1 activates T lymphocytes, inhibits smooth muscle proliferation and thrombosis, is important in gonadal function and raises cyclic AMP levels in many tissues. It is a good candidate for a key factor lost in aging. Moderate food restriction, the only manoeuvre which consistently slows aging in homoiotherms, raises D6D activity by 300%. Other factors important in regulating D6D and the conversion of GLA to PGE1 are zinc, pyridoxine, ascorbic acid, the pineal hormone, melatonin, and possibly vitamin B3. GLA administration to humans has been found to lower blood pressure and cholesterol, and to cause clinical improvement in patients with Sjogren's syndrome, scleroderma and alcoholism. These diseases are associated with some features of accelerated aging. The proposition that D6D loss is not only a marker of aging but a cause of some of its major manifestations is amenable to experimental test even in humans. The blocked enzyme can be by-passed by giving GLA directly
The regulation of prostaglandin biosynthesis by the manipulation of essential fatty acid metabolism.
Horrobin DF.
Rev Pure Appl Pharmacol Sci. 1983 Oct; 4(4):339-83.
Two of the most widely used groups of drugs in medical practice are the non-steroidal anti-inflammatory agents and the steroids. Both act by modulating the conversion of essential fatty acids to prostaglandins, leukotrienes and related substances. The actions of these drugs are therefore likely to be modified by variations in the levels of substrates, notably arachidonic acid and dihomogammalinolenic acid, available for metabolism by lipoxygenase and cyclo-oxygenase enzymes. Yet most doctors who use the drugs and many scientists who carry out research on them seem unaware of the factors which determine the concentrations of the substrate essential fatty acids. This paper reviews in detail the metabolism of essential fatty acids and the interactions between nutrient intake and subsequent metabolism which determine the concentrations of the individual fatty acids. It is concluded that the efficacy of drug therapy as far as the steroids and the non-steroidal anti-inflammatory drugs are concerned could be substantially enhanced by greater knowledge of the factors which determine the availability of substrates to the key enzymes
Docosahexaenoic acid-enriched foods: production and effects on blood lipids.
Horrocks LA, Yeo YK.
Lipids. 1999; 34 Suppl:S313.
Health benefits of docosahexaenoic acid (DHA).
Horrocks LA, Yeo YK.
Pharmacol Res. 1999 Sep; 40(3):211-25.
Docosahexaenoic acid (DHA) is essential for the growth and functional development of the brain in infants. DHA is also required for maintenance of normal brain function in adults. The inclusion of plentiful DHA in the diet improves learning ability, whereas deficiencies of DHA are associated with deficits in learning. DHA is taken up by the brain in preference to other fatty acids. The turnover of DHA in the brain is very fast, more so than is generally realized. The visual acuity of healthy, full-term, formula-fed infants is increased when their formula includes DHA. During the last 50 years, many infants have been fed formula diets lacking DHA and other omega-3 fatty acids. DHA deficiencies are associated with foetal alcohol syndrome, attention deficit hyperactivity disorder, cystic fibrosis, phenylketonuria, unipolar depression, aggressive hostility, and adrenoleukodystrophy. Decreases in DHA in the brain are associated with cognitive decline during aging and with onset of sporadic Alzheimer disease. The leading cause of death in western nations is cardiovascular disease. Epidemiological studies have shown a strong correlation between fish consumption and reduction in sudden death from myocardial infarction. The reduction is approximately 50% with 200 mg day(-1)of DHA from fish. DHA is the active component in fish. Not only does fish oil reduce triglycerides in the blood and decrease thrombosis, but it also prevents cardiac arrhythmias. The association of DHA deficiency with depression is the reason for the robust positive correlation between depression and myocardial infarction. Patients with cardiovascular disease or Type II diabetes are often advised to adopt a low-fat diet with a high proportion of carbohydrate. A study with women shows that this type of diet increases plasma triglycerides and the severity of Type II diabetes and coronary heart disease. DHA is present in fatty fish (salmon, tuna, mackerel) and mother's milk. DHA is present at low levels in meat and eggs, but is not usually present in infant formulas. EPA, another long-chain n-3 fatty acid, is also present in fatty fish. The shorter chain n-3 fatty acid, alpha-linolenic acid, is not converted very well to DHA in man. These longchain n-3 fatty acids (also known as omega-3 fatty acids) are now becoming available in some foods, especially infant formula and eggs in Europe and Japan. Fish oil decreases the proliferation of tumour cells, whereas arachidonic acid, a longchain n-6 fatty acid, increases their proliferation. These opposite effects are also seen with inflammation, particularly with rheumatoid arthritis, and with asthma. DHA has a positive effect on diseases such as hypertension, arthritis, atherosclerosis, depression, adult-onset diabetes mellitus, myocardial infarction, thrombosis, and some cancers
Fish and omega-3 fatty acid intake and risk of coronary heart disease in women.
Hu FB, Bronner L, Willett WC, et al.
JAMA. 2002 Apr 10; 287(14):1815-21.
CONTEXT: Higher consumption of fish and omega-3 fatty acids has been associated with a lower risk of coronary heart disease (CHD) in men, but limited data are available regarding women. OBJECTIVE: To examine the association between fish and long-chain omega-3 fatty acid consumption and risk of CHD in women. DESIGN, SETTING, AND PARTICIPANTS: Dietary consumption and follow-up data from 84 688 female nurses enrolled in the Nurses' Health Study, aged 34 to 59 years and free from cardiovascular disease and cancer at baseline in 1980, were compared from validated questionnaires completed in 1980, 1984, 1986, 1990, and 1994. MAIN OUTCOME MEASURES: Incident nonfatal myocardial infarction and CHD deaths. RESULTS: During 16 years of follow-up, there were 1513 incident cases of CHD (484 CHD deaths and 1029 nonfatal myocardial infarctions). Compared with women who rarely ate fish (<1 per month), those with a higher intake of fish had a lower risk of CHD. After adjustment for age, smoking, and other cardiovascular risk factors, the multivariable relative risks (RRs) of CHD were 0.79 (95% confidence interval [CI], 0.64-0.97) for fish consumption 1 to 3 times per month, 0.71 (95% CI, 0.58-0.87) for once per week, 0.69 (95% CI, 0.55-0.88) for 2 to 4 times per week, and 0.66 (95% CI, 0.50-0.89) for 5 or more times per week (P for trend =".001)." Similarly, women with a higher intake of omega-3 fatty acids had a lower risk of CHD, with multivariable RRs of 1.0, 0.93, 0.78, 0.68, and 0.67 (P<.001 for trend) across quintiles of intake. For fish intake and omega-3 fatty acids, the inverse association appeared to be stronger for CHD deaths (multivariate RR for fish consumption 5 times per week, 0.55 [95% CI, 0.33-0.90] for CHD deaths vs 0.73 [0.51-1.04]) than for nonfatal myocardial infarction. CONCLUSION: Among women, higher consumption of fish and omega-3 fatty acids is associated with a lower risk of CHD, particularly CHD deaths
Dietary n-3 fatty acids influence the lipid composition and physical properties of liver microsomal membranes in diabetic rats.
Igal A, Gomez Dumm NT.
Prostaglandins Leukot Essent Fatty Acids. 1997 Mar; 56(3):245-52.
We examined the effect of n-3 fatty acid consumption on the lipid composition and physical properties of liver microsomal membranes in normal and experimental diabetic rats. Lipid analysis showed a significant increase in the cholesterol:phospholipid ratio in membranes of normal animals fed n-3 fatty acids as well as in both groups of diabetic rats. These changes would be in part responsible for the higher fluorescent polarization of DPH (1,6-diphenyl-1,3,5 hexatriene) observed in the diabetic groups compared with the normal ones. These alterations were partially compensated by an increase in the amount of phosphatidylcholine in the diabetic rats fed on n-3 fatty acids. However, proteins also play a role in determining the physical properties of the liver microsomes because in the liposomes derived from them, the fluorescent polarization of DPH decreased in the diabetics fed n-3 fatty acids. Measurements of fluorescence anisotropy of n-AS (2-, 7 and 12 (9 anthroyloxy) stearic acid) probes revealed a restricted rotational mobility in the middle zone of the bilayer. Consistently with this finding there was an elevation in the calculated unsaturation density of the fatty acids at the carbon 8 position. These experiments confirm the lipid abnormalities that take place in experimental diabetes and they show further that n-3 fatty-acid administration causes certain compensatory, and thus beneficial, changes in these abnormalities
Doxazosin and the ALLHAT Study .
IHP, Information for Health Professionals.
2000
Prospective study of fat and protein intake and risk of intraparenchymal hemorrhage in women.
Iso H, Stampfer MJ, Manson JE, et al.
Circulation. 2001 Feb 13; 103(6):856-63.
BACKGROUND:-Dietary animal fat and protein have been inversely associated with a risk of intraparenchymal hemorrhage in ecological studies. METHODS AND RESULTS: In 1980, 85 764 women in the Nurses' Health Study cohort, who were 34 to 59 years old and free of diagnosed cardiovascular disease and cancer, completed dietary questionnaires. From these questionnaires, we calculated fat and protein intake. By 1994, after 1.16 million person-years of follow-up, 690 incident strokes, including 74 intraparenchymal hemorrhages, had been documented. Multivariate-adjusted risk of intraparenchymal hemorrhage was higher among women in the lowest quintile of energy-adjusted saturated fat intake than at all higher levels of intake (relative risk [RR], 2.36; 95% CI, 1.10 to 5.09; P:=0.03). For trans unsaturated fat, the corresponding RR was 2.50 (95% CI, 1.35 to 4.65; P:=0.004). Animal protein intake was inversely associated with risk (RR in the highest versus lowest quintiles, 0.32; 95% CI, 0.10 to 1.00; P:=0.04). The excess risk associated with low saturated fat intake was observed primarily among women with a history of hypertension (RR, 3.66; 95% CI, 1.09 to 12.3; P=0.04), but such an interaction was not seen for trans unsaturated fat or animal protein. These nutrients were not related to risk of other stroke subtypes. Dietary cholesterol and monounsaturated and polyunsaturated fat were not related to risk of any stroke subtype. CONCLUSIONS: Low intake of saturated fat and animal protein was associated with an increased risk of intraparenchymal hemorrhage, which may help to explain the high rate of this stroke subtype in Asian countries. The increased risk with low intake of saturated fat and trans unsaturated fat is compatible with the reported association between low serum total cholesterol and risk
Effects of strength training on muscle power and serum hormones in middle-aged and older men.
Izquierdo M, Hakkinen K, Ibanez J, et al.
J Appl Physiol. 2001 Apr; 90(4):1497-507.
Effects of 16-wk strength training on maximal strength and power performance of the arm and leg muscles and serum concentrations [testosterone (T), free testosterone (FT), and cortisol] were examined in 11 middle-aged (M46; 46 +/- 2 yr) and 11 older men (M64; 64 +/- 2 yr). During the 16-wk training, the relative increases in maximal strength and muscle power output of the arm and leg muscles were significant in both groups (P < 0.05-0.001), with no significant differences between the two groups. The absolute increases were higher (P < 0.01-0.05) in M46 than in M64 mainly during the last 8 wk of training. No significant changes were observed for serum T and FT concentrations. Analysis of covariance showed that, during the 16-wk training period, serum FT concentrations tended to decrease in M64 and increase in M46 (P < 0.05). However, significant correlations between the mean level of individual serum T and FT concentrations and the individual changes in maximal strength were observed in a combined group during the 16-wk training (r = "0.49" and 0.5, respectively; P < 0.05). These data indicate that a prolonged total strength-training program would lead to large gains in maximal strength and power load characteristics of the upper and lower extremity muscles, but the pattern of maximal and power development seemed to differ between the upper and lower extremities in both groups, possibly limited in magnitude because of neuromuscular and/or age-related endocrine impairments
Clinical Advisory Statement. Importance of systolic blood pressure in older Americans.
Izzo JL, Jr., Levy D, Black HR.
Hypertension. 2000 May; 35(5):1021-4.
Is the relation of systolic blood pressure to risk of cardiovascular disease continuous and graded, or are there critical values?
Kannel WB, Vasan RS, Levy D.
Hypertension. 2003 Oct; 42(4):453-6.
Biochem Pharmacol Science.
Kellis JT Jr NSVL.
Biochem Pharmacol Science. 1984;(225):1032-4.
EFA & Eicosanoids. Omega-6 and omega-3 polyunsaturated fatty acids in experimental atherosclerosis regression.
Khalilov EM.
1997;
none
Dietary docosahexaenoic acid (22: 6n-3) prevents the development of hypertension in SHRSP.
Kimura S, Minami M, Saito H, et al.
Clin Exp Pharmacol Physiol Suppl. 1995 Dec; 22(1):S308-S309.
1. We previously reported that hypertension in stroke-prone spontaneously hypertensive rats (SHRSP) caused renal membrane phospholipid degradation. Renal phospholipase A2 activity increased and membranous phospholipids decreased along with age in SHRSP. Membranous abnormalities induced by membrane fluidity and calcium permeability changes may contribute to the elevation of blood pressure in SHRSP. DHA, a major component of fish oil, constitutes a part of membrane phospholipid acylchains. 2. The purpose of this study was to clarify the effect of DHA on the relationship between the renal function and the development of hypertension in SHRSP. 3. Six week old male SHRSP were fed a semi-purified diet supplemented with DHA (0, 1 and 5%) for 14 weeks. 4. The systolic blood pressure of control SHRSP (DHA 0%) significantly increased from 120.2 mmHg to 202.9 mmHg. This increase in systolic blood pressure was significantly inhibited in a dose-dependent manner by 1 and 5% DHA diet to 167.8 to 149.8 mmHg, respectively. 5. Serum creatinine concentration and blood urea nitrogen (BUN) were significantly lower in DHA (5%)-treated SHRSP than in the control SHRSP. 6. These results indicate that DHA prevents the development of hypertension in SHRSP, which is associated with changes in renal function
Modern Nutrition in Health and Disease.
Kotchen TA KJ.
1999; 9:1217-27.
none
Effects of heavy-resistance training on hormonal response patterns in younger vs. older men.
Kraemer WJ, Hakkinen K, Newton RU, et al.
J Appl Physiol. 1999 Sep; 87(3):982-92.
To examine the adaptations of the endocrine system to heavy-resistance training in younger vs. older men, two groups of men (30 and 62 yr old) participated in a 10-wk periodized strength-power training program. Blood was obtained before, immediately after, and 5, 15, and 30 min after exercise at rest before and after training and at rest at -3, 0, 6, and 10 wk for analysis of total testosterone, free testosterone, cortisol, growth hormone, lactate, and ACTH analysis. Resting values for insulin-like growth factor (IGF)-I and IGF-binding protein-3 were determined before and after training. A heavy-resistance exercise test was used to evaluate the exercise-induced responses (4 sets of 10-repetition maximum squats with 90 s of rest between sets). Squat strength and thigh muscle cross-sectional area increased for both groups. The younger group demonstrated higher total and free testosterone and IGF-I than the older men, training-induced increases in free testosterone at rest and with exercise, and increases in resting IGF-binding protein-3. With training the older group demonstrated a significant increase in total testosterone in response to exercise stress along with significant decreases in resting cortisol. These data indicate that older men do respond with an enhanced hormonal profile in the early phase of a resistance training program, but the response is different from that of younger men
Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits.
Kritchevsky D, Tepper SA, Wright S, et al.
J Am Coll Nutr. 2000 Aug; 19(4):472S-7S.
OBJECTIVE: To determine effects of conjugated linoleic acid (CLA) on establishment and progression of experimentally-induced atherosclerosis in rabbits. METHODS: For establishment of atherosclerosis, New Zealand White rabbits were fed a semipurified diet containing 0.1% to 0.2% cholesterol for 90 days. Some groups were fed diet and CLA. For effects on progression of atherosclerosis, rabbits with established atherosclerosis were fed a semipurified diet +/- CLA for 90 days. RESULTS: At dietary levels as low as 0.1%, CLA inhibited atherogenesis. At dietary levels of 1%, CLA caused substantial (30%) regression of established atherosclerosis. This is the first example of substantial regression of atherosclerosis being caused by diet alone. CONCLUSION: Dietary CLA is an effective inhibitor of atherogenesis and also causes regression of established atherosclerosis
Are free radicals involved in the pathobiology of human essential hypertension?
Kumar KV, Das UN.
Free Radic Res Commun. 1993; 19(1):59-66.
Possible involvement of reactive oxygen species and nitric oxide in the pathogenesis of human essential hypertension was investigated. It was observed that both superoxide anion and hydrogen peroxide production by polymorphonuclear leukocytes and the plasma levels of lipid peroxides are higher in uncontrolled essential hypertension compared with normal controls. Nitric oxide levels measured as its stable metabolite nitrite, as an index of nitric oxide synthesis, revealed its levels to be low in hypertensive patients. Superoxide anion, hydrogen peroxide, lipid peroxides and nitric oxide levels reverted to normal values after the control of hypertension by drugs. The concentrations of anti-oxidants such as vitamin E and superoxide dismutase were found to be decreased in patients with uncontrolled hypertension. Several anti-hypertensive drugs inhibited lipid peroxidation in vitro. Angiotensin-II, a potent vasoconstrictor, stimulated free radical generation in normal leukocytes which could be blocked by calmodulin antagonists. These results suggest that an increase in free radical generation and a simultaneous decrease in the production of nitric oxide and anti-oxidants such as SOD and vitamin E occurs in essential hypertension. This increase in free radical generation can inactivate prostacyclin and nitric oxide and decrease their half life which can lead to an increase in peripheral vascular resistance and hypertension
Usefulness of coenzyme Q10 in clinical cardiology: a long-term study.
Langsjoen H, Langsjoen P, Langsjoen P, et al.
Mol Aspects Med. 1994; 15 Suppl:s165-s175.
Over an eight year period (1985-1993), we treated 424 patients with various forms of cardiovascular disease by adding coenzyme Q10 (CoQ10) to their medical regimens. Doses of CoQ10 ranged from 75 to 600 mg/day by mouth (average 242 mg). Treatment was primarily guided by the patient's clinical response. In many instances, CoQ10 levels were employed with the aim of producing a whole blood level greater than or equal to 2.10 micrograms/ml (average 2.92 micrograms/ml, n = 297). Patients were followed for an average of 17.8 months, with a total accumulation of 632 patient years. Eleven patients were omitted from this study: 10 due to non-compliance and one who experienced nausea. Eighteen deaths occurred during the study period with 10 attributable to cardiac causes. Patients were divided into six diagnostic categories: ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), primary diastolic dysfunction (PDD), hypertension (HTN), mitral valve prolapse (MVP) and valvular heart disease (VHD). For the entire group and for each diagnostic category, we evaluated clinical response according to the New York Heart Association (NYHA) functional scale, and found significant improvement. Of 424 patients, 58 per cent improved by one NYHA class, 28% by two classes and 1.2% by three classes. A statistically significant improvement in myocardial function was documented using the following echocardiographic parameters: left ventricular wall thickness, mitral valve inflow slope and fractional shortening. Before treatment with CoQ10, most patients were taking from one to five cardiac medications. During this study, overall medication requirements dropped considerably: 43% stopped between one and three drugs. Only 6% of the patients required the addition of one drug. No apparent side effects from CoQ10 treatment were noted other than a single case of transient nausea. In conclusion, CoQ10 is a safe and effective adjunctive treatment for a broad range of cardiovascular diseases, producing gratifying clinical responses while easing the medical and financial burden of multidrug therapy
Treatment of essential hypertension with coenzyme Q10.
Langsjoen P, Langsjoen P, Willis R, et al.
Mol Aspects Med. 1994; 15 Suppl:S265-S272.
A total of 109 patients with symptomatic essential hypertension presenting to a private cardiology practice were observed after the addition of CoQ10 (average dose, 225 mg/day by mouth) to their existing antihypertensive drug regimen. In 80 per cent of patients, the diagnosis of essential hypertension was established for a year or more prior to starting CoQ10 (average 9.2 years). Only one patient was dropped from analysis due to noncompliance. The dosage of CoQ10 was not fixed and was adjusted according to clinical response and blood CoQ10 levels. Our aim was to attain blood levels greater than 2.0 micrograms/ml (average 3.02 micrograms/ml on CoQ10). Patients were followed closely with frequent clinic visits to record blood pressure and clinical status and make necessary adjustments in drug therapy. Echocardiograms were obtained at baseline in 88% of patients and both at baseline and during treatment in 39% of patients. A definite and gradual improvement in functional status was observed with the concomitant need to gradually decrease antihypertensive drug therapy within the first one to six months. Thereafter, clinical status and cardiovascular drug requirements stabilized with a significantly improved systolic and diastolic blood pressure. Overall New York Heart Association (NYHA) functional class improved from a mean of 2.40 to 1.36 (P < 0.001) and 51% of patients came completely off of between one and three antihypertensive drugs at an average of 4.4 months after starting CoQ10. Only 3% of patients required the addition of one antihypertensive drug. In the 9.4% of patients with echocardiograms both before and during treatment, we observed a highly significant improvement in left ventricular wall thickness and diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment of hypertrophic cardiomyopathy with coenzyme Q10.
Langsjoen PH, Langsjoen A, Willis R, et al.
Mol Aspects Med. 1997; 18 Suppl:S145-S151.
Hypertrophic cardiomyopathy (HCM) is manifested by severe thickening of the left ventricle with significant diastolic dysfunction. Previous observations on the improvement in diastolic function and left ventricular wall thickness through the therapeutic administration of coenzyme Q10 (CoQ10) in patients with hypertensive heart disease prompted the investigation of its utility in HCM. Seven patients with HCM, six non-obstructive and one obstructive, were treated with an average of 200 mg/day of CoQ10 with mean treatment whole blood CoQ10 level of 2.9 micrograms/ml. Echocardiograms were obtained in all seven patients at baseline and again 3 or more months post-treatment. All patients noted improvement in symptoms of fatigue and dyspnea with no side effects noted. The mean interventricular septal thickness improved significantly from 1.51 +/- 0.17 cm to 1.14 +/- 0.13 cm, a 24% reduction (P < 0.002). The mean posterior wall thickness improved significantly from 1.37 +/- 0.13 cm to 1.01 +/- 0.15 cm, a 26% reduction (P < 0.005). Mitral valve inflow slope by pulsed wave Doppler (EF slope) showed a non-significant trend towards improvement, 1.55 +/- 0.49 m/sec2 to 2.58 +/- 1.18 m/sec2 (P < 0.08). The one patient with subaortic obstruction showed an improvement in resting pressure gradient after CoQ10 treatment (70 mmHg to 30 mmHg)
Conjugated linoleic acid reduces arachidonic acid content and PGE2 synthesis in murine keratinocytes.
Liu KL, Belury MA.
Cancer Lett. 1998 May 15; 127(1-2):15-22.
Dietary conjugated linoleic acid (CLA) is associated with decreased 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotion in mouse skin. In addition, CLA decreases TPA-induced prostaglandin E synthesis and ornithine decarboxylase activity in cultured keratinocytes compared with linoleic acid (LA) and arachidonic acid (AA). When LA or CLA was added to keratinocyte cell cultures, the amounts of each of these cellular fatty acids increased significantly in a dose-dependent manner. Furthermore, LA treatment was associated with increased cellular AA while the AA content of keratinocytes was reduced when cultures were treated with CLA. Moreover, CLA (16 microg/ml) was more potent than LA at decreasing the level of 14C-AA incorporated into cellular phosphatidylcholine. In order to determine the effect of CLA on arachidonate-derived PGE2, the release of 14C-AA and 14C-PGE2 synthesis was measured in cultures pre-treated with LA/14C-AA or CLA/14C-AA for 12 h. The amount of 14C-AA release induced by TPA in CLA/14C-AA pre-treated cultures was significantly lower than cultures pre-treated with LA/14C-AA. Furthermore, TPA-induced 14C-PGE2 was significantly lower in cultures pre-treated with CLA/14C-AA compared with cultures pre-treated with LA/14C-AA. The effects of LA and CLA on AA composition of phospholipids and subsequent arachidonate-derived PGE2 synthesis will provide insight into the anti-promoter mechanisms of CLA
Diet and sex hormone-binding globulin.
Longcope C, Feldman HA, McKinlay JB, et al.
J Clin Endocrinol Metab. 2000 Jan; 85(1):293-6.
The serum concentration of sex hormone-binding globulin (SHBG) is inversely related to weight and in animal studies is inversely related to protein intake. As SHBG can affect the biological activity of testosterone and estradiol, we wished to determine the role of protein intake on SHBG levels in men. Using data from the Massachusetts Male Aging Study we examined cross-sectional relationships between dietary components and SHBG levels in 1552 men (aged 40-70 yr) for whom these factors were known. Analyzed by multiple regression, controlling for testosterone and estradiol levels, age (P<0.001) and fiber intake (P = "0.02)" were positively correlated to SHBG concentration, whereas body mass index (P<0.001) and protein intake (P<0.03) were negatively correlated to SHBG concentration. The intakes of calories, fat (animal or vegetable), and carbohydrate were not related to SHBG concentration. We conclude that age and body mass index are major determinants of SHBG concentrations in older men, and fiber and protein intake are also significant contributors to SHBG levels, but total caloric intake and the intake of carbohydrate or fat are not significant. Thus, diets low in protein in elderly men may lead to elevated SHBG levels and decreased testosterone bioactivity. The decrease in bioavailable testosterone can then result in declines in sexual function and muscle and red cell mass, and contribute to the loss of bone density
Putative mechanism of blood pressure reduction induced by increases in dietary calcium intake.
Luft FC.
Am J Hypertens. 1990 Aug; 3(8 Pt 2):156S-60S.
An increase in dietary calcium intake lowers blood pressure in spontaneously hypertensive rats and in some patients with arterial hypertension. The mechanisms by which this decrease come about are not clear. A membrane-stabilizing effect wrought by an increase in extracellular calcium would appear unlikely, since the increases in extracellular calcium concentration with increased dietary intake are minimal. Calcium regulatory hormones may be the mediators, and a cybernetic framework has been suggested. Striking defects have been reported in the calcium handling and hormonal household of the spontaneously hypertensive rat. However, a clear cut relationship in terms of a hormonal "template" has not yet been identified in prospective experiments. Data have been presented to show that increased calcium intake has a direct effect on regulatory areas in the brain. However, the mechanisms by which such a response would be mediated are entirely unknown. Increased calcium intake may induce natriuresis. It has been suggested that increased calcium intake helps the "salt sensitive"; however, prospective studies to this effect have not been presented. Increased calcium intake may induce phosphaturia. However, the evidence that blood pressure lowering effects are mediated by phosphate depletion are unconvincing. Some evidence suggests that increased calcium intake may influence local regulatory processes which in turn influences cell integrity and growth. At this point, a unifying hypothesis is not available. However, the clues to various possibilities are intriguing
C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease.
Madsen T, Skou HA, Hansen VE, et al.
Am J Cardiol. 2001 Nov 15; 88(10):1139-42.
The acute-phase reactant C-reactive protein (CRP) has emerged as an independent risk factor for coronary artery disease. Experimental and clinical studies provide evidence of anti-inflammatory effects of n-3 polyunsaturated fatty acids (PUFA) derived from fish. We have studied the effect of marine n-3 PUFA on CRP levels in 269 patients referred for coronary angiography because of clinical suspicion of coronary artery disease. All patients filled out a food questionnaire regarding fish intake. The n-3 PUFA content of granulocyte membranes was determined and the concentration of CRP in serum was measured using a highly sensitive assay. The results were related to angiographic findings. CRP was significantly higher in patients with significant coronary stenoses than in those with no significant angiographic changes (p <0.001), but the CRP levels were not associated with the number of diseased vessels. Subjects with CRP levels in the lower quartile had a significantly higher content of docosahexaenoic acid (DHA) in granulocytes than subjects with CRP levels in the upper quartile (p = "0.02)," and in a multivariate linear regression analysis, DHA was independently correlated to CRP (R(2) = "0.179;" p = "0.003)." The inverse correlation between CRP and DHA may reflect an anti-inflammatory effect of DHA in patients with stable coronary artery disease and suggest a novel mechanism by which fish consumption may decrease the risk of coronary artery disease
In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychologic stress.
Maes M, Christophe A, Bosmans E, et al.
Biol Psychiatry. 2000 May 15; 47(10):910-20.
BACKGROUND: Psychologic stress in humans induces the production of proinflammatory cytokines, such as interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6), and that of the negative immunoregulatory cytokine, IL-10. An imbalance of omega6 to omega3 polyunsaturated fatty acids (PUFAs) in the peripheral blood causes an overproduction of proinflammatory cytokines. The omega3 PUFAs reduce the production of proinflammatory cytokines. METHODS: This study examines whether an imbalance in omega6 to omega3 PUFAs in human blood predicts a greater production of proinflammatory cytokines in response to psychologic stress. Twenty-seven university students had serum sampled a few weeks before and after as well as 1 day before a difficult oral examination. We determined the omega6 and omega3 fractions in serum phospholipids as well as the ex vivo production of IFN-gamma, TNF-alpha, IL-6, IL-10, and IL-5 by diluted whole blood stimulated with polyclonal activators. RESULTS: Academic examination stress significantly increased the ex vivo, stimulated production of IFN-gamma, TNF-alpha and IL-10, and the IFN-gamma/IL-5 production ratio. Subjects with lower serum omega3 PUFA levels or with a higher omega6/omega3 ratio had significantly greater stress-induced TNF-alpha and IFN-gamma responses than subjects with higher serum omega3 PUFAs and a lower omega6/omega3 ratio, respectively. Subjects with lower serum omega3 PUFA levels or with a higher omega6/omega3 ratio had a significantly higher stress-induced increase in the IFN-gamma/IL-5 ratio than the remaining subjects. CONCLUSIONS: Psychologic stress induces a Th-1-like or proinflammatory response in some subjects. An imbalance in the omega6 to omega3 PUFA ratio appears to predispose humans toward an exaggerated Th-1-like response and an increased production of monocytic cytokines, such as TNF-alpha, in response to psychologic stress. The results suggest that increased omega3 PUFA levels may attenuate the proinflammatory response to psychologic stress
[Homocysteine as a nonlipid factor in the pathogenesis of atherosclerosis].
Magott M.
Postepy Hig Med Dosw. 1998; 52(3):259-67.
Genetic abnormalities in two metabolic steps in homocysteine degradation: transsulfuration and remetylation can cause raised plasma homocysteine concentration. Homocysteine appeared to be an independent arteriosclerotic risk factor in the coronary, cerebral and peripheral circulation and elevated homocysteine levels have been found in chronic renal failure patients undergoing hemodialysis treatment and in transplant patients as well. Homocysteine has a direct toxic effect on endothelial cells, reduces normal activation of protein C by endothelial cells, increases the binding of Lp(a) to plasmin-modified fibrin, induces tissue factor procoagulant activity and inhibits the cofactor activity of thrombomodulin. Treatment with folic acid and piridoxine can lower the high level of homocysteine and should be associated with a clinical benefit
Integrative approaches to hypertension.
Maizes V.
Clinics Fam Practice. 2002;(4):895-905.
Dietary calcium and blood pressure: modifying factors in specific populations.
McCarron DA, Morris CD, Young E, et al.
Am J Clin Nutr. 1991 Jul; 54(1 Suppl):215S-9S.
Epidemiologic findings continue to add to the body of evidence supporting a relationship between calcium intake and blood pressure. These findings also indicate that there is a threshold of the potential protective effect of adequate calcium intake, below which the risk of hypertension increases at a greater rate. The set point of this threshold, estimated at 700-800 mg/d, may be modified by a variety of factors including dietary patterns and components, lifestyle, and genetics. This may explain, at least in part, the heterogeneous response observed in dietary-intervention studies. In animal models of hypertension it was shown that greater amounts of calcium must be given to cause a blood pressure change comparable with that in normal animals, suggesting that in high-risk human populations in which calcium metabolism may be disordered, calcium intake may have to be increased to amounts greater than 700-800 mg/d to demonstrate the blood-pressure-lowering effect. Calcium intake at or above the currently recommended daily allowance of 800 mg could be of potential benefit to certain racial groups, individuals ingesting excessive alcohol, and pregnant women, all of whom generally consume low amounts of calcium and who are at higher risk of developing hypertension
Role of adequate dietary calcium intake in the prevention and management of salt-sensitive hypertension.
McCarron DA.
Am J Clin Nutr. 1997 Feb; 65(2 Suppl):712S-6S.
During the past decade, a credible body of evidence has emerged supporting the concept that maintaining an adequate dietary mineral intake, specifically of calcium, magnesium, and potassium, protects against high blood pressure in humans. Observational and interventional studies in humans and extensive use of laboratory models showed that a significant portion of blood pressure variability in response to sodium chloride can be linked to the adequacy of the mineral content of the diet. This review summarizes the observational data from several large databases showing that when adults meet or exceed the recommended dietary allowances of calcium, potassium, and magnesium, the simultaneous ingestion of a diet high in sodium chloride is not associated with elevated arterial pressure. In fact, a higher sodium chloride intake in these adults is most likely associated with the lowest blood pressure in the society. This interaction between adequacy of mineral intake and protection against salt sensitivity in humans provides an important opportunity for further improving blood pressure control in our society. Educating individuals to maintain, on a daily basis, adequate intakes of calcium, potassium, and magnesium rather than limit their sodium chloride is a viable health recommendation that individuals can implement to reduce their risk of sodium chloride-induced hypertension
Importance of dietary calcium in hypertension.
McCarron DA.
J Am Coll Nutr. 1998 Feb; 17(1):97-9.
Homocysteine and vascular disease.
McCully KS.
Nat Med. 1996 Apr; 2(4):386-9.
Homocysteine and endothelial dysfunction: a link with cardiovascular disease.
McDowell IF, Lang D.
J Nutr. 2000 Feb; 130(2S Suppl):369S-72S.
The nature of the link between homocysteine and cardiovascular disease has not yet been clearly established. Impaired endothelium-independent vasodilatation is an early feature of vascular disease. In human studies, methionine loading, which acutely elevates plasma homocysteine, induces endothelial dysfunction. Folate therapy, which lowers homocysteine, enhances endothelial function. This is consistent with, but not proof of, homocysteine toxicity to endothelium in vivo. Homocysteine, in high concentration, can induce endothelial dysfunction in vitro. This is accompanied by increased superoxide production, which when inhibited, restores normal endothelial function. These observations suggest that homocysteine may induce vascular endothelial dysfunction by a mechanism involving reactive oxygen species
The inconsistent effects of calcium supplements upon blood pressure in primary hypertension.
Meese RB, Gonzales DG, Casparian JM, et al.
Am J Med Sci. 1987 Oct; 294(4):219-24.
The effects of 800 mg of elemental calcium per day (calcium carbonate or calcium citrate) on blood pressure were compared with a placebo in a controlled randomized, crossover, double-blinded trial involving 26 patients with uncomplicated primary hypertension. Each patient took two of the three forms of therapy orally for 8-week intervals with a 2-week washout period in between. Standing mean blood pressure rose an average of 5.7 mm Hg on placebo, rose an average of 0.5 mm Hg on calcium carbonate, and fell an average of 2.2 mm Hg on calcium citrate. Changes in sitting mean pressures averaged +1.9 mm Hg on placebo, -0.4 mm Hg on calcium carbonate, and -0.4 mm Hg on calcium citrate. Some patients had a fall, others had a rise in blood pressure on each form of calcium. Similarly, inconsistent responses were noted among the nine patients who took both forms of calcium. Neither initial nor post-treatment biochemical measures nor patient characteristics were predictive of the blood pressure response. Combinations of various measures and characteristics analyzed by the multiple regression technique explained only 30% of the overall variability in blood pressure. Therefore, until ways can be found to predict the response, calcium supplements should not be routinely prescribed for the treatment of hypertension and, if given for any indication, blood pressure should be monitored
Effect of dietary trans fatty acids on high-density and low-density lipoprotein cholesterol levels in healthy subjects.
Mensink RP, Katan MB.
N Engl J Med. 1990 Aug 16; 323(7):439-45.
BACKGROUND. Fatty acids that contain a trans double bond are consumed in large amounts as hydrogenated oils, but their effects on serum lipoprotein levels are unknown. METHODS. We placed 34 women (mean age, 26 years) and 25 men (mean age, 25 years) on three mixed natural diets of identical nutrient composition, except that 10 percent of the daily energy intake was provided as oleic acid (which contains one cis double bond), trans isomers of oleic acid, or saturated fatty acids. The three diets were consumed for three weeks each, in random order. RESULTS. On the oleic acid diet, the mean (+/- SD) serum values for the entire group for total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were 4.46 +/- 0.66. 2.67 +/- 0.54, and 1.42 +/- 0.32 mmol per liter (172 +/- 26, 103 +/- 21, and 55 +/- 12 mg per deciliter), respectively. On the trans-fatty-acid diet, the subjects' mean HDL cholesterol level was 0.17 mmol per liter (7 mg per deciliter) lower than the mean value on the diet high in oleic acid (P less than 0.0001; 95 percent confidence interval, 0.13 to 0.20 mmol per liter). The HDL cholesterol level on the saturated-fat diet was the same as on the oleic acid diet. The LDL cholesterol level was 0.37 mmol per liter (14 mg per deciliter) higher on the trans-fatty-acid diet than on the oleic acid diet (P less than 0.0001; 95 percent confidence interval, 0.28 to 0.45 mmol per liter) and 0.47 mmol per liter (18 mg per deciliter) higher on the saturated-fat diet (P less than 0.001; 95 percent confidence interval, 0.39 to 0.55 mmol per liter) than on the oleic acid diet. The effects on lipoprotein levels did not differ between women and men. CONCLUSIONS. The effect of trans fatty acids on the serum lipoprotein profile is at least as unfavorable as that of the cholesterol-raising saturated fatty acids, because they not only raise LDL cholesterol levels but also lower HDL cholesterol levels
Effect of dietary cis and trans fatty acids on serum lipoprotein[a] levels in humans.
Mensink RP, Zock PL, Katan MB, et al.
J Lipid Res. 1992 Oct; 33(10):1493-501.
Serum lipoprotein[a] (Lp[a]) is a strong risk factor for coronary heart disease. We therefore examined the effect of dietary fatty acid composition on serum Lp[a] levels in three strictly controlled experiments with healthy normocholesterolemic men and women. In Expt. I, 58 subjects consumed a control diet high in saturated fatty acids for 17 days. For the next 36 days, 6.5% of total energy intake from saturated fatty acids was replaced by monounsaturates plus polyunsaturates (monounsaturated fatty acid diet; n = 29) or by polyunsaturates alone (polyunsaturated fatty acid diet; n = 29). Both diets caused a slight, nonsignificant, increase in median Lp[a] levels, with no difference between diets. In Expt. II, 10% of energy from the cholesterol-raising saturated fatty acids (lauric, myristic, and palmitic acid) was replaced by oleic acid or by trans-monounsaturated fatty acids. Each of the 59 participants received each diet for 3 weeks in random order. The median level of Lp[a] was 26 mg/l on the saturated fatty acid diet; it increased to 32 mg/l (P less than 0.020) on the oleic acid diet and to 45 mg/l (P less than 0.001) on the trans-fatty acid diet. The difference in Lp[a] between the trans-fatty acid and the oleic acid diets was also highly significant (P less than 0.001). Expt. III involved 56 subjects; all received 8% of energy from stearic acid, from linoleic acid, or from trans-monounsaturates, for 3 weeks each. All other nutrients were equal.(ABSTRACT TRUNCATED AT 250 WORDS)
Gamma linolenic acid attenuates cardiovascular responses to stress in borderline hypertensive rats.
Mills DE, Summers MR, Ward RP.
Lipids. 1985 Sep; 20(9):573-7.
The purpose of the present study was to investigate the effects of gamma linolenic acid (GLA) on cardiovascular responses to psychosocial stress (isolation) and to pressor hormones in the genetically borderline hypertensive rat (SHR X WKY). Adult male SHR X WKY were divided into two groups following five weeks of group housing. One group (GLA) received eight weeks constant flow osmotic pumps releasing 0.04 mg GLA in olive oil/kg-hr, while the second group received dummy pumps (DUM). One week following pump implantation, each group was divided into two subgroups and exposed to a four-week experimental period of either continued group housing (no stress) or isolation (stress). A two-week recovery period of group housing followed the experimental period. Blood pressur |