Life Extension Magazine

Life Extension Magazine November 2004

LE Magazine November 2004
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Treatment of dyslipidemia in high-risk patients: too little, too late.
Evidence that lowering low-density cholesterol (LDL-C) reduces coronary events and mortality is now overwhelming and is reflected in treatment guidelines from around the world. The Joint European Guidelines recommend an LDL-C goal of <3.0 mmol/l in high-risk subjects. The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP)-III guidelines suggest an even more aggressive approach in high-risk individuals, with a recommended LDL-C goal of <2.6 mmol/l. Large numbers of high-risk patients are still not achieving the more conservative goals recommended in the Joint European Guidelines, let alone the more aggressive LDL-C target recommended in the new NCEPATP-III guidelines. The recognition in the NCEP ATP-III guidelines that a high-density lipoprotein cholesterol (HDL-C) level <1.0 mmol/l represents an important risk factor highlights the emergence of HDL-C as a key player in the genesis of coronary heart disease (CHD) and as a potential target for therapy. This may be especially important in people with insulin resistance with or without type 2 diabetes. There is evidence from the Helsinki Heart Study and the more recent Veterans Affairs HDL Intervention Trial (VA-HIT), both of which used gemfibrozil as the active agent, that the observed reduction in coronary events was correlated with the magnitude of the increase in HDL-C. The challenge for future management of high-risk individuals will be not only to reduce the level of LDL-C to below 2.6 mmol/l but also to increase HDL-C to levels above 1.0 mmol/l.

Int J Clin Pract Suppl. 2002 Jul;(130):15-9

Serum total cholesterol concentrations and awareness, treatment, and control of hypercholesterolemia among US adults: findings from the National Health and Nutrition Examination Survey, 1999 to 2000.

BACKGROUND: Serum cholesterol concentrations have decreased in the US population. Whether the decline continued during the 1990s is unknown. METHODS AND RESULTS: We used data from 4,148 men and women aged > or =20 years who had a total cholesterol determination or reported using cholesterol-lowering medications and who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2000 (this is a cross-sectional health examination survey of the US population), and we compared the results with data from 15,719 participants in NHANES III (1988 to 1994). For all adults, the age-adjusted mean total cholesterol concentration decreased from 5.31 mmol/L (205 mg/dL) in NHANES III to 5.27 mmol/L (203 mg/dL) in NHANES 1999 to 2000 (P=0.159). The age-adjusted mean total cholesterol concentration decreased by 0.02 mmol/L (0.7 mg/dL) among men (P=0.605) and 0.06 mmol/L (2.3 mg/dL) among women (P=0.130). Significant decreases were observed among men aged > or =75 years, black men, and Mexican-American women. Among participants who had a total cholesterol concentration > or =5.2 mmol/L (200 mg/dL) or who reported using cholesterol-lowering medications, 69.5% reported having had their cholesterol checked, 35.0% were aware that they had hypercholesterolemia, 12.0% were on treatment, and 5.4% had a total cholesterol concentration <5.2 mmol/L (200 mg/dL) after age adjustment. CONCLUSIONS: The mean serum total cholesterol concentration of the adult US population in 1999 to 2000 has changed little since 1988 to 1994. The low percentage of adults with controlled blood cholesterol concentration suggests the need for a renewed commitment to the prevention, treatment, and control of hypercholesterolemia.

Circulation. 2003 May 6;107(17):2185-9

Contemporary awareness and understanding of cholesterol as a risk factor: results of an American Heart Association national survey.

BACKGROUND: Public awareness and understanding of risk factors for atherosclerotic vascular disease are essential for successful primary and secondary prevention. The American Heart Association is committed to reducing cardiovascular disease. METHODS: A professional market survey company conducted a structured national telephone survey of English-speaking adults 40 years and older on behalf of the American Heart Association. Regional and sex quotas were imposed on the sample, and responses were weighted to match the 1999 census projections for region of the country, age, sex, and race. RESULTS: Interviews were completed with 1,163 adults 40 years and older. A national probability sample of 1,114 was created. Of the final sample, 28.5% were 65 years or older, 56.1% were women, and 86.5% were white. Although 91.2% of respondents stated that it was “important to them personally to have a healthy cholesterol level” (77.6% extremely or very important), 51% did not know their own level. Only 40.2% were aware of national guidelines for cholesterol management, and 53.1% either did not know or overestimated the correct desirable total cholesterol level for a healthy adult. When asked what sources of information they rely on the most, 66.8% identified physicians, while only 3.7% rely primarily on the Internet. CONCLUSIONS: Public understanding of cholesterol management is suboptimal. Physicians have a unique opportunity, on the basis of public attitudes and access, to improve cholesterol education.

Arch Intern Med. 2003 Jul 14;163(13):1597-600

Use of nutritional supplements for the prevention and treatment of hypercholesterolemia.

OBJECTIVE: Hypercholesterolemia is a major risk factor for the development of coronary artery disease. Studies have shown that several vitamins and nutritional supplements may contribute to a reduction in total and low-density lipoprotein cholesterol. This goal of this study was to document the use of vitamins and nutritional supplements that may treat or prevent hypercholesterolemia. METHODS: Secondary analysis of the National Health and Nutrition Examination Survey III responses from 13,990 patients were available to use for making population estimates. RESULTS: Of those individuals with a known diagnosis of hypercholesterolemia, 3.6% were taking at least one vitamin or nutritional supplement to decrease cholesterol levels. For individuals trying to prevent hypercholesterolemia, 1.2% were using one of these vitamin or nutritional supplements. Only 0.7% of individuals without or trying to prevent hypercholesterolemia used one of these specific supplements. We used multivariate analysis to control for several factors, and individuals with a diagnosis of hypercholesterolemia had an adjusted odds ratio of 2.10 (95% confidence interval, 1.38-3.21) for vitamin use compared with those without or trying to prevent high cholesterol. Those trying to prevent hypercholesterolemia had an adjusted odds ratio of 0.69 (95% confidence interval, 0.48-1.00) for vitamin use compared with those without or trying to prevent high cholesterol. CONCLUSIONS: The use of vitamins and nutritional supplements that may reduce total and low-density lipoprotein cholesterol levels is low in the United States. Future research is needed to confirm the effectiveness of these products, examine the quality and purity of currently available products, and explore whether using these supplements are an adequate low-cost alternative to pharmaceuticals now available.

Nutrition. 2003 May;19(5):415-8

Treating hyperlipidemia for the primary prevention of coronary disease. Are higher dosages of lovastatin cost-effective?

OBJECTIVE: To compare the average and marginal life-time cost-effectiveness of increasing dosages of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, for the primary prevention of coronary heart disease (CHD). METHODS: We estimated the lifelong costs and benefits of the modification of lipid levels achieved with lovastatin based on published studies and a validated CHD prevention computer model. Patients were middle-aged men and women without CHD, with mean total serum cholesterol levels of 6.67, 7.84, and 9.90 mmol/L (258, 303, and 383 mg/dL), and high-density lipoprotein cholesterol levels of 1.19 mmol/L (46 mg/dL), as described in clinical trials. We estimated the cost per year of life saved for dosages of lovastatin ranging from 20 to 80 mg/d that reduced the total cholesterol level between 17% and 34%, and increased high-density lipoprotein cholesterol level between 4% and 13%. RESULTS: After discounting benefits and costs by 5% annually, the average cost-effectiveness of lovastatin, 20 mg/d, ranged from $11,040 to $52,463 for men and women. The marginal cost-effectiveness of 40 mg/d vs 20 mg/d remained in this range ($25,711 to $60,778) only for persons with baseline total cholesterol levels of 7.84 mmol/L (303 mg/dL) or higher. However, the marginal cost-effectiveness of lovastatin, 80 mg/d vs 40 mg/d, was prohibitively expensive ($99,233 to $716,433 per year of life saved) for men and women, irrespective of the baseline total cholesterol level. CONCLUSIONS: Assuming that $50,000 per year of life saved is an acceptable cost-effectiveness ratio, treatment with lovastatin at a dosage of 20 mg/d is cost-effective for middle-aged men and women with baseline total cholesterol levels of 6.67 mmol/L (258 mg/dL) or higher. At current drug prices, treatment with 40 mg/d is also cost-effective for total cholesterol levels of 7.84 mmol/L (303 mg/dL) or higher. However, treatment with 80 mg/d is not cost-effective for primary prevention of CHD.

Arch Intern Med. 1998 Feb 23;158(4):375-81

Serum cholesterol levels and in-hospital mortality in the elderly.

PURPOSE: Although total cholesterol levels among middle-aged persons correlate with long-term mortality from all causes, this association remains controversial in older persons. We explored whether total cholesterol levels were independently associated with in-hospital mortality among elderly patients. METHODS: We analyzed data from a large collaborative observational study, the Italian Group of Pharmacoepidemiology in the Elderly (GIFA), which collected data on hospitalized patients. A total of 6,984 patients aged 65 years or older who had been admitted to 81 participating medical centers during four survey periods (from 1993 to 1998) were enrolled. Patients were divided into four groups based on total cholesterol levels at hospital admission: <160 mg/dL (n = 2115), 160 to 199 mg/dL (n = 2210), 200 to 239 mg/dL (n = 1719), and >or=240 mg/dL (n = 940). RESULTS: Patients (mean [+/- SD] age, 78 +/- 7 years) were hospitalized for an average of 15 +/- 10 days. The mean total cholesterol level was 186 +/- 49 mg/dL. A total of 202 patients died during hospitalization. Mortality was inversely related to cholesterol levels (<160 mg/dL: 5.2% [110/2115]; 160-199 mg/dL: 2.2% [49/2210]; 200-239 mg/dL: 1.6% [27/1719]; and >or=240 mg/dL: 1.7% [16/940]; P for linear trend <0.001). After adjustment for potential confounders (demographic characteristics, smoking, alcohol use, indicators of nutritional status, markers of frailty, and comorbid conditions), low cholesterol levels continued to be associated with in-hospital mortality. Compared with patients who had cholesterol levels <160 mg/dL, the odds ratios for in-hospital mortality were 0.49 (95% confidence interval [CI]: 0.34 to 0.70) for participants with cholesterol levels of 160 to 199 mg/dL, 0.41 (95% CI: 0.26 to 0.65) for those with cholesterol levels of 200 to 239 mg/dL, and 0.56 (95% CI: 0.32 to 0.98) for those with cholesterol levels >or=240 mg/dL. These estimates were similar after further adjustment for inflammatory markers and after excluding patients with liver disease. CONCLUSIONS: Among older hospitalized adults, low serum cholesterol levels appear to be an independent predictor of short-term mortality.

Am J Med. 2003 Sep;115(4):265-71.

Low total cholesterol and increased risk of dying: are low levels clinical warning signs in the elderly? Results from the Italian Longitudinal Study on Aging.

OBJECTIVES: To analyze the relationship between serum total cholesterol (TC) and all-cause mortality, taking into account various potential confounders. DESIGN: Population-based prospective cohort study. SETTING: Older Italians residing in the general community. PARTICIPANTS: Four thousand five hundred twenty-one men and women aged 65-84. MEASUREMENTS: Vital status data were available for 1992-95. The hazard ratios of dying for subjects in the second, third, and fourth quartiles compared with the first quartile of TC were computed using Cox proportional hazards, adjusting for lifestyle factors, anthropomorphic and biochemical measures, preexisting medical conditions, and frailty indicators. RESULTS: Blood samples were obtained from 3,295 (73%) of the participants, of whom 399 died during almost 3 years of follow-up. Low TC was associated with a higher risk of death. Those with TC in the second, third, and fourth quartiles (TC>189 mg/dL or 4.90 mmol/L) had lower hazard ratios (HRs) of death than subjects in the first quartile (0.57, 95% confidence interval (CI) = 0.38-0.87; 0.56, 95% CI = 0.36-0.88; and 0.53, 95% CI = 0.33-0.84, respectively). Few subjects taking lipid-lowering drugs (LLDs) were in the lowest quartile of cholesterol, suggesting that these individuals have low TC values for reasons other than LLD use. CONCLUSION: Subjects with low TC levels (<189 mg/dL) are at higher risk of dying even when many related factors have been taken into account. Although more data are needed to clarify the association between TC and all-cause mortality in older individuals, physicians may want to regard very low levels of cholesterol as potential warning signs of occult disease or as signals of rapidly declining health.

J Am Geriatr Soc. 2003 Jul;51(7):991-6