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Life Extension Magazine

LE Magazine September 2003
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Cholesterol

Statins and risk of polyneuropathy: a case-control study.
BACKGROUND: Several case reports and a single epidemiologic study indicate that use of statins occasionally may have a deleterious effect on the peripheral nervous system. The authors therefore performed a population-based study to estimate the relative risk of idiopathic polyneuropathy in users of statins. METHOD: The authors used a population-based patient registry to identify first-time-ever cases of idiopathic polyneuropathy registered in the five-year period 1994 to 1998. For each case, validated according to predefined criteria, 25 control subjects were randomly selected among subjects from the background population matched for age, sex and calendar time. The authors used a prescription register to assess exposure to drugs and estimated the odds ratio of use of statins (ever and current use) in cases of idiopathic polyneuropathy compared with control subjects. RESULTS: The authors verified a diagnosis of idiopathic polyneuropathy in 166 cases. The cases were classified as definite (35), probable (54) or possible (77). The odds ratio linking idiopathic polyneuropathy with statin use was 3.7 (95% CI 1.8 to 7.6) for all cases and 14.2 (5.3 to 38.0) for definite cases. The corresponding odds ratios in current users were 4.6 (2.1 to 10.0) for all cases and 16.1 (5.7 to 45.4) for definite cases. For patients treated with statins for two or more years the odds ratio of definite idiopathic polyneuropathy was 26.4 (7.8 to 45.4). CONCLUSIONS: Long-term exposure to statins may substantially increase the risk of polyneuropathy.

Neurology 2002 May 14;58(9):1333-7

A new approach to cholesterol.
Although much is known about hypercholesterolemia and the associated risk for the development of atherosclerosis, very little research has focused on altered cholesterol biosynthesis. Recent discovery that the biochemical basis for the human malformation syndrome, Smith-Lemli-Opitz syndrome appears to lie in altered cholesterol biosynthesis has changed this situation. Cholesterol has an extraordinary important functions in organism. Recommendations to lower serum cholesterol are widespread, yet low serum cholesterol is associated with poorly understood morbidity. Cholesterol is still an enigmatic, essential metabolite and much remains to learn about it.

Cas Lek Cesk 2001 Nov 8;140(22):685-7

Fatal rhabdomyolysis caused by cerivastatin.
Cerivastatin was recently withdrawn from the market after the report of more than 30 deaths in the United States among patients receiving a combination of cerivastatin and gemfibrozil, a fibrate which is no longer on the Belgian market. The cause of death was attributed to severe rhabdomyolysis. Cases were also reported among patients treated by cerivastatin only. Recommendations for better use of lipid-lowering drugs are given in order to optimize the benefit/risk ratio of such treatment.

Rev Med Liege 2001 Aug;56(8):592-4.

New criteria of normal serum lipid levels in Japanese children: the nationwide study.
AIM: To make new criteria of serum lipid levels in current Japanese children using the large nationwide data provided from Japan Association of Health Service for the analysis. METHODS: The subjects were schoolchildren who received screening and care programs for lifestyle related diseases since 1993 to 1999. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and triglyceride (TG) levels were measured, and low-density lipoprotein cholesterol (LDLC) levels were calculated. Serum lipid levels were analyzed by age and sex. For each serum lipid, we extracted age- and sex-specific group which the mean value was not statistically different from that in 1999 by Student’s t-test analysis. RESULTS: The level below the 75th percentile was defined to be acceptable, from the 75th to 95th to be borderline and over the 95th to be high in TC/LDLC. The level below the fifth percentile in HDLC was defined to be low and the level over the 95th percentile in TG to be high. Therefore, TC level was categorized as follows: acceptable < 190 mg/dL; borderline 190 to 219 mg/dL; and high > 220 mg/dL. The LDLC level was also categorized into: acceptable < 110 mg/dL; borderline 110 to 139 mg/dL; and high > 140 mg/dL. The cut-off value in TG was determined to be 140 mg/dL and in HDLC was 40 mg/dL. CONCLUSIONS: This new criteria should prove valuable in health strategies for rational prevention and intervention in children. It should be emphasized to provide some intervention for Japanese children immediately.

Pediatr Int 2002 Dec;44(6):596-601.

Hormone replacement therapy in postmenopausal women and its effects on plasma lipid levels.
Postmenopausal women run the same risks of coronary heart disease as men. The lipid alterations observed at this time reflect increased blood levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a), and reduced high-density lipoprotein cholesterol (HDL-C) levels. These changes lead to a higher risk of coronary artery disease, and hormonal therapy has a favorable effect on lipid metabolism. In this paper we review the literature on hormone replacement therapy (HRT) in postmenopausal women with the emphasis on the role of lipids in the pathogenesis of coronary heart disease, and on the action of estrogens and their correlation with progestogens, as well as routes of HRT administration. We conclude that the HRT changes the lipid profile in a potentially anti-atherogenic direction, usually reducing LDL-C and increasing HDL-C and triglycerides. Otherwise, for postmenopausal women with established coronary disease HRT is not recommended.

Clin Chem Lab Med 2002 May;40(5):446-51.

Hypocholesterolemia during mixed manic episodes.
BACKGROUND: An association of relatively low serum cholesterol with both depression and suicide has been reported. Depressive symptoms, including suicidality, are defining features of mixed mania. Few studies have considered differences in cholesterol levels in subjects during mixed bipolar episodes. METHODS: Fasting serum cholesterol levels obtained from 174 subjects evaluated during mixed and pure manic episodes were compared using ANOVA statistics. Sex was included in the analysis and age was used as a covariate. Cholesterol levels in the total manic cohort and in the mixed and pure manic subgroups were compared with national norms. RESULTS: Fasting serum cholesterol levels were lower in the mixed manic subtype compared to the pure manic subtype. As expected, cholesterol levels increased with age. No differences were noted between males and females. Cholesterol levels were lower in both the mixed and pure manic subtypes when compared with national norms. CONCLUSION: Fasting serum cholesterol levels are low in manic patients, especially during mixed bipolar episodes. Cholesterol, which has been reported to be a negative acute phase reactant, may be lower during mixed states as a result of an immune activation.

Eur Arch Psychiatry Clin Neurosci 2002 Jun;252(3):110-4

The cholesterol controversy.
OBJECTIVE: To provide information about the controversy associated with lowering of cholesterol concentrations to prevent coronary heart disease (CHD). DATA SOURCES: Studies, review articles and editorials identified from MEDLINE searches (from 1966 to 1995) and bibliographies of identified articles. STUDY SELECTION: Studies, review articles and editorials addressing controversial issues related to cholesterol lowering. DATA EXTRACTION: Pertinent information was selected and the data synthesized into a review format. DATA SYNTHESIS: Hypercholesterolemia is a well-known CHD risk factor. Reduction of serum cholesterol concentrations has been shown to reduce the incidence of CHD. Unfortunately, cholesterol lowering also appears to increase the risk for cancer, accidental and violent death, stroke and oddly enough, CHD when certain medications are used. CONCLUSIONS: Significant reductions in serum cholesterol concentrations can be achieved with cholesterol-lowering interventions. However, the benefits associated with cholesterol reduction may not outweigh the risks in all patients with hypercholesterolemia. Cholesterol-lowering interventions should be recommended with caution in patients at increased risk of cancer, stroke and depression. Caution should also be used when recommending fibric acid derivatives for patients with existing CHD.

Ann Pharmacother 1996 May;30(5):495-500

Cardiovascular disease: a historic perspective.
Cardiovascular disease (CVD) is the leading cause of death and disability in the United States and in most industrialized nations. Major breakthroughs to modern day cardiovascular/lipid research have been attributed to the findings of the Framingham Heart Study and Gofman and colleagues who made associations between lipoprotein levels (LDL, VLDL and HDL) and CVD. Unfortunately, half of all CVD patients have none of the established coronary risk factors (hypertension, hypercholesterolemia, cigarette smoking, diabetes mellitus, obesity) and new strategies for identifying patients need be considered. Although there remains little disagreement regarding the necessity to lower elevated plasma cholesterol levels, there remains much controversy regarding appropriate dietary means of accomplishing this goal. The National Cholesterol Education Program (1993) proposed a dietary reduction (Step I and Step II diets) to the percent saturated fat and cholesterol consumed by at-risk patients. Many currently question the effectiveness of these diets. An alternative diet, replacing saturated fats by monounsaturated fats (olive oil), has attracted recent attention. While diet modification is considered the foundation of primary treatment, other interventions are frequently required. Although early drug trials demonstrated that agents such as nicotinic acid, clofibrate, gemfibrozil, bile acid-binding resins generally slowed progression of atherosclerotic lesions, lowered plasma cholesterol levels and decreased mortality from CVD, the greatest advance to current drug therapy involved the discovery of the “statins” (HMG-CoA reductase inhibitors). In the current work, mechanisms for vascular dysfunction resulting in myocardial ischemia were explored and potential nutritional (dietary) and pharmacologic interventions were reviewed.

Jpn J Vet Res 2000 Nov;48(2-3):147-66.

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