Abstract
BackgroundWhether the suggested inverse association between total cholesterol and mortality in old age varies according to cause of death and use of cholesterol medications remains to be elucidated. The aim of this study was to assess the associations of total cholesterol with cardiovascular and non-cardiovascular mortality in old age, and to explore whether their associations vary by use of cholesterol-lowering medications.MethodsThe study participants included 3090 older adults (age ≥ 60 years, 63.7% women) from a population-based cohort study, i.e., the Swedish National study on Aging and Care in Kungsholmen, Stockholm. At baseline (2001–2004), data on demographic factors, lifestyles, cardiovascular risk factors, use of medications, global cognitive function, mobility limitation, and apolipoprotein E genotype were collected through interviews, clinical examinations, laboratory tests as well as from the Swedish national patient register. Vital statistics data (e.g., date and causes of death) till December 31, 2011 for all participants were derived from Swedish cause of death register. Data were analyzed using Cox proportional hazards model for all-cause mortality and Fine-Gray competing risks regression model for cause-specific mortality controlling for multiple potential confounders.ResultsDuring 23,196 person-years of follow-up (median per person, 7.5 years), 1059 (34.3%) participants died. Compared to normal total cholesterol (<5.18 mmol/l), borderline-high (5.18–6.21 mmol/l) and high (≥6.22 mmol/l) total cholesterol were associated with a decreased risk of all-cause mortality, with the multiple-adjusted hazard ratio (95% confidence interval, CI) of 0.71 (0.61–0.83) and 0.68 (0.57–0.80), respectively (P for trend <0.001). The competing risk regression models revealed that the reduced all-cause mortality associated with high total cholesterol (≥6.22 mmol/l)) was mainly due to the reduced risk of non-cardiovascular mortality (hazard ratio = 0.67, 95% CI = 0.51–0.88). These associations were statistically evident only among individuals without use of cholesterol-lowering medications.ConclusionsThe inverse association between high total cholesterol and reduced all-cause mortality in older adults is primarily due to non-cardiovascular mortality, especially among those who are not treated with cholesterol-lowering medications.
Highlights
Whether the suggested inverse association between total cholesterol and mortality in old age varies according to cause of death and use of cholesterol medications remains to be elucidated
The Rotterdam Study found that higher total cholesterol was associated with a lower risk of noncardiovascular mortality in older adults, and the strength of the inverse association was increased with every decade increase in age [6]
During 23,196 person-years of follow-up, 1059 (34.3%) participants died. Compared with those who were still alive during follow-up, those who died during follow-up were older (P < 0.001), less likely to have university education or above (P = 0.020), less likely to be former smokers (P = 0.022) or current smokers (P < 0.001), more likely to be physically inactive (P < 0.001), had a lower level of total cholesterol (P < 0.001), had a higher prevalence of diabetes (P < 0.001), cognitive impairment (P < 0.001), and mobility limitation (P < 0.001), and less likely to be an apolipoprotein E (APOE) ε4 carrier (P = 0.046) after controlling for age
Summary
Whether the suggested inverse association between total cholesterol and mortality in old age varies according to cause of death and use of cholesterol medications remains to be elucidated. The Rotterdam Study found that higher total cholesterol was associated with a lower risk of noncardiovascular mortality in older adults (age ≥ 65 years), and the strength of the inverse association was increased with every decade increase in age [6]. Another review of observational studies and randomized controlled trials suggested that use of statins may even increase the all-cause mortality among very old people without cardiovascular diseases [8]. It remains uncertain whether use of cholesterol-lowering medications (e.g., statins) might modify the association of total cholesterol with all-cause and cause-specific mortality among older adults
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