Lipid-lowering treatment to the end? A review of observational studies and RCTs on cholesterol and mortality in 80+-year olds

Abstract

People aged 80 or older are the fastest growing population in high-income countries. One of the most common causes of death among the elderly is the cardiovascular disease (CVD). Lipid-lowering treatment is common, e.g. one-third of 75-84-year-old Swedes are treated with statins. The assumption that hypercholesterolaemia is a risk factor at the highest ages seems to be based on extrapolation from younger adults. A review of observational studies shows a trend where all-cause mortality was highest when total cholesterol (TC) was lowest ('a reverse J-shaped' association between TC and all-cause mortality). Low TC (<5.5 mmol/l) is associated with the highest mortality rate in 80+-year olds. No clear optimal level of TC was identified. A review of the few randomised controlled trials including 80+-year olds did not provide evidence of an effect of lipid-lowering treatment on total mortality in 80+-year-old people. There is not sufficient data to recommend anything regarding initiation or continuation of lipid-lowering treatment for the population aged 80+, with known CVD, and it is even possible that statins may increase all-cause mortality in this group of elderly individuals without CVD.

Figure 1.

Search strategy and selection criteria.

Figure 2.

All-cause mortality and cholesterol in the elderly. At the x-axis, the cholesterol was plotted as an exact measure of TC (mmol/l), even though most studies had each point responding to an interval of cholesterol, where we chose the middle of this interval as the point to plot. In the top panel, one study has two U-shaped plots corresponding to women and men, respectively [15], and one study a reverse J-shaped configuration [9]. The middle panel showed six studies: three describing ‘a reverse J-shaped configuration’ [10, 16, 19], two describing an almost declining curve [10, 15] and one study an inverted U-shaped configuration [12]. The lower panel was one study showing a fluctuating mortality in women and a decreasing mortality when TC increased in men [14]. The three studies not included did not report specific calculations on the total mortality risk in relation to the TC in the 80+-year-old participants [12, 18, 21]. Among those two studies described, no association between TC and all-cause mortality was found, whereas one study found the higher total mortality related to low TC disappearing when adjusted for low HDL and albumin among people aged 70 and above [12, 18, 21].