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Low Serum Cholesterol
Low Serum Cholesterol
Hazardous to Health?
1. Elaine N. Meilahn , MD + Author Affiliations 1. From the London School of Hygiene and Tropical Medicine, Department of Epidemiology, University of London, London. 1. Correspondence to Elaine N. Meilahn, MD, the London School of Hygiene and Tropical Medicine, Department of Epidemiology, University of London, Keppel Street, London WC1E 7HT, UK. Key Words: Is having very low cholesterol levels hazardous to health? There is evidence to suggest that it might be. In 1990, an NIH conference concluded from a metaanalysis of 19 studies that men and, to a lesser extent, women with a total serum cholesterol level below 4.2 mmol/L (160 mg/dL) (6th percentile) exhibited about a 10% to 20% excess total mortality compared with those with a cholesterol level between 4.2 and 5.2 mmol/L (160 to 199 mg/dL).1 Specifically, excess causes of death included cancer (primarily lung and hematopoietic), respiratory and digestive disease, violent death (suicide and trauma), and hemorrhagic stroke. On the basis of this and other reports, a debate arose on whether recommendations for lowering cholesterol should be directed at the entire population or only toward those at high risk of coronary heart disease. Would shifting the entire cholesterol distribution downward subject those individuals at the low end of the scale to increased risk of noncardiovascular disease?2 3 A major obstacle to finding an answer to this question has been that the determinants of low cholesterol are poorly understood. Why does someone living in a westernized country have a very low serum cholesterol
in population-based study samples compared with employed cohorts.ahajournals. Iribarren et al9 go beyond the usual classification of “low cholesterol” based on a single measure and instead have examined future disease risk according to whether cholesterol level was stable over about 6 years or whether low cholesterol resulted from falling blood cholesterol levels.7 Epidemiological studies generally have been unable to distinguish individuals with low cholesterol caused by underlying disease or aberrant health habits from those with “naturally occurring” low cholesterol.org/content/92/9/2365. whereas low (<4. possibly. with mortality follow-up extending for up to 16 years.7 mmol/L. alcohol abuse and ill health.6 or.4 an underlying condition causing hypocholesterolemia such as an acute infection5 or “preclinical” disease.long 2/7 . they measured total serum cholesterol at two time points.8 The current report from Iribarren et al9 in this issue of Circulation attempts to make this distinction in an effort to determine prospectively whether having a low serum cholesterol level is hazardous to health. Two additional pieces of evidence that suggest that low cholesterol is not a circ. Their findings provide evidence that the association previously reported between low cholesterol and noncoronary mortality probably reflected the cholesterol-lowering metabolic consequences of long-term subclinical disease rather than a hazard associated with low cholesterol per se.4/13/13 Low Serum Cholesterol concentration? Apart from consuming an “atypical” very-low-fat. Among nearly 6000 healthy Japanese-American men enrolled in the Honolulu Heart Study. the reasons include “genetic resistance” to excess dietary cholesterol. falling levels of cholesterol were linked to an excess risk of hepatic disease and cancer in particular. adverse health behavior such as alcohol abuse. The investigators proposed that the discrepancy in results was probably due to a higher frequency of risk factors associated with low cholesterol. whereas population-based studies did show a relationship. <180 mg/dL) but stable levels over time were not associated with excess risk. eg. lowcholesterol diet. Results showed the expected association of elevated cholesterol with coronary disease. This conclusion is consistent with results of a recent meta-analysis10 of causespecific mortality (including unpublished data on noncardiovascular causes of death) from 10 large cohort studies and 2 international studies that concluded that reduced serum cholesterol is not related to excess mortality among cohorts of employed individuals. In addition.
previous studies have excluded from analyses deaths within the first 2. Moreover.15 It is important to recognize that individuals with serum cholesterol sufficiently elevated to require drug or diet therapy are certainly a different group altogether from individuals with low cholesterol caused by lifestyle or genetic factors. In particular.ahajournals.4/13/13 Low Serum Cholesterol causal factor for noncardiovascular disease are the normal to extended life expectancy experienced by individuals with genetically determined hypobetacholesterolemia11 and populations with low average blood cholesterol levels. 5. or 10 years of follow-up. Finally.1 A further limitation of the present report6 is the relatively small number of subjects with sustained low-cholesterol level (n=376). although the association between low cholesterol and disease appears to be much weaker for women than for men. does not result in a “low” serum cholesterol level. including suicide. such as the Japanese and Greeks. at least two examples of long-term morbidity leading to cholesterol reduction are hepatitis B virus infection13 and chronic respiratory disease resulting in repeated respiratory infections. a reduction in cholesterol from 240 mg/dL or higher. The ability to detect any but large increases in risk of disease is limited by the size of the group “exposed” to persistent low cholesterol. This is plausible.long 3/7 .12 One strength of the investigation by Iribarren et al9 is its ability (albeit limited to two measures) to track cholesterol over time. reflecting the generally elevated serum cholesterol level among westernized populations.org/content/92/9/2365.14 A limitation of the study by Iribarren et al9 is the exclusion of women from the study population. cholesterollowering treatment has been related to an excess of violent deaths. even by as much as 20%. it is important to note that the study by Iribarren et al9 was not designed to address the issue of whether cholesterol-lowering treatment is associated with excess risk of noncoronary deaths. The dearth of information on the effects of low cholesterol and cholesterol lowering in women and children is one rationale for not supporting population-based efforts to reduce cholesterol levels. who do not exhibit an excess of noncardiovascular disease deaths. The circ.3 This issue remains unresolved. The results found by Iribarren et al7 suggest that a drop in serum cholesterol may occur over a decade before disease is diagnosed. In an effort to eliminate the possible cholesterol-lowering effects of latent disease.
1992. 1992.org/content/92/9/2365.. Benfante R. ↵ Hulley SB. The public health significance of the report by Iribarren et al is the evidence it provides that population-based recommendations for lowering cholesterol levels will not lead to adverse health consequences. et al. Will lowering population levels of serum cholesterol affect total mortality? Expectations from the Honolulu Heart Program. Grove JS.86:1026-1029. Thus. They conclude that the reported association of low cholesterol levels with increased mortality is probably due to cholesterol-lowering effects of existing disease.4/13/13 Low Serum Cholesterol present report9 did not distinguish individuals with a reduction in cholesterol resulting from treatment for hypercholesterolemia from those with a spontaneous drop.86:1046-1060.45:333-346. Report of the conference on low blood cholesterol: mortality associations. Their results offer reassurance for individuals with “naturally occurring” low cholesterol levels and support for the notion that national guidelines to reduce cholesterol are consistent with public health interests. Copyright © 1995 by American Heart Association References 1. Abstract/FREE Full Text  2. ↵ Frank JW.long 4/7 . Footnotes The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. Health policy on blood cholesterol: time to change direction. Circulation . McMillan G. 1992.ahajournals. circ. Iso H. Reed DM. Higgins M. Walsh JMB. Newman TB. ↵ Jacobs DR. the current findings reported by Iribarren et al9 cannot be related directly to clinical trials of reduction of hypercholesterolemia. Blackburn H. 3. Circulation . Reed D. J Clin Epidemiol. Editorial.
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