By David Fiore, MD

Professor of Family Medicine, University of Nevada, Reno

Dr. Fiore reports no financial relationships relevant to this field of study.

SYNOPSIS: In this retrospective review of data from the Women’s Health Initiative, researchers found that neither low levels of high-density lipoprotein nor high levels of low-density lipoprotein were associated with predicted survival in older women. This finding is consistent with other studies of cholesterol and mortality in the elderly.

SOURCE: Maihofer AX, Shadyab AH, Wild RA, LaCroix AZ. Associations between serum levels of cholesterol and survival to age 90 in postmenopausal women. J Am Geriatr Soc 2020;68:288-296.

There is evidence showing that high levels of low-density lipoprotein (LDL) and low levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk for cardiovascular events and death among the general population. Further, research has shown that treatment with statins can lower this risk in the general population. However, it is unclear if these relationships hold true in the elderly. The 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease does not address lipids or statin therapy in patients older than age 75 years.1 The authors of other reviews have found conflicting evidence of the benefit of treating dyslipidemia in the elderly, especially in primary prevention. A 2014 meta-analysis revealed a benefit in treatment for secondary prevention and a trend toward a benefit for primary prevention in the elderly.2,3

More recent studies have cast doubt on the clinical significance of dyslipidemia in the elderly and on the benefits of treatment. In 2016, Ravnskov et al published a review of 19 cohort studies with 68,094 subjects older than age 60 years. They found an inverse relationship between LDL cholesterol and mortality.4 In 2019, Nanna et al used individual level data from the National Institutes of Health Pooled Cohorts (which included Framingham, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Cardiovascular Health Study).5 Looking at data from 2,667 adults with a median age of 78 and median LDL cholesterol of 117 mg/dL, the authors found no difference in event rates (stroke, myocardial infarction, or cardiovascular death) in those with or without hyperlipidemia. This lack of correlation held regardless of risk factors.

Maihofer et al used data from the Women’s Health Initiative (WHI) to examine the relationship between LDL and HDL and survival status and self-reported mobility. The WHI started in 1993 at 40 clinical centers across the United States, with 161,808 participants between the ages of 50 and 79 years. In 2005, 115,400 surviving participants re-enrolled for an extension study. In 2010, 93,540 re-enrolled for another extension. A total of 27,940 participants had lipid assays; of those, 4,838 were selected for the current analysis based on their ability to reach their 90th birthday by Aug. 31, 2016. Of these, another 1,371 were excluded due to vascular or cardiovascular disease, cancer, or statin use, leaving 3,567 for primary analysis, with 117 of these lost to follow-up. Mobility status was determined by mailed surveys using the 36-Item Short Form Health Survey (SF-36).

Women with higher LDL levels were more likely to be alcohol drinkers; white; and to have higher triglyceride, blood pressure, and total cholesterol (but lower HDL) levels. They were less likely to be college educated or have a history of diabetes that required treatment.

Women with higher HDL levels were more likely to have lower systolic blood pressure readings, to have a lower body mass index, to be African American, and to be college educated. Further, these subjects reported very good or excellent self-rated health, engaged in more physical activity, and recorded higher total cholesterol (but lower LDL and triglyceride) levels.

After adjusting for age and race/ethnicity, higher HDL levels were significantly associated with higher odds of living to age 90 years vs. the lowest quartile (odds ratio, 1.24; 95% confidence interval, 1.03-1.50). However, after the authors adjusted for lifestyle and medical factors, the association was attenuated and no longer statistically significant. Higher HDL levels also correlated with intact mobility to age 90, but was attenuated when the authors adjusted for lifestyle factors (but not by medical factors).

COMMENTARY

There were some important limitations to this (and similar prior) studies. First, remember we are talking about primary prevention. If an elderly patient already has cardiovascular disease, the current recommendations (aggressive treatment of dyslipidemia) still hold. Second, the authors used data from the WHI, which means this information was only for elderly women. There also were significant confounders, such as race, education, and diabetes, for which the researches tried to account, but this always makes it more difficult to interpret the significance of the results. Third, and what I struggle with in practice, is how to manage the elderly or very elderly patient who has been on a statin for primary prevention for years and has never experienced a cardiovascular disease event. Should we stop or continue the statin? Since there does not appear to be good evidence either way, shared decision-making, with an honest discussion of what we do not know, may be the best approach.

REFERENCES

  1. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;74:1376-1414.
  2. Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of statin therapy in older people: A meta-analysis of individual participant data from 28 randomised controlled trials. Lancet 2019;393:407-415.
  3. Cheung BMY, Lam KSL. Never too old for statin treatment? Lancet 2019;393:379-380.
  4. Ravnskov U, Diamond DM, Hama R, et al. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: A systematic review. BMJ Open 2016;6:e010401.
  5. Nanna MG, Navar AM, Wojdyla D, Peterson ED. The association between low-density lipoprotein cholesterol and incident atherosclerotic cardiovascular disease in older adults: Results from the National Institutes of Health Pooled Cohorts. J Am Geriatr Soc 2019;67:2560-2567.