Non-Cardiovascular Mortality, Low-Density Lipoprotein Cholesterol and Statins: A Meta-Regression Analysis

Abstract

Background: As of today, the effect of statins on non-cardiovascular mortality is still being debated. Single studies have not been able to provide definite answers. We performed a meta-regression analysis on randomized statin trials in order to provide evidence that non-cardiovascular mortality is related to statin treatment and low-density lipoprotein (LDL) cholesterol plasma level. Methods: We selected 29 randomized controlled trials of statins versus placebo, a total of 90,480 patients, with a follow-up of >12 months. Baseline and follow-up LDL levels and all-cause, cardiovascular and non-cardiovascular mortality were recorded. Weighted linear regression analysis was carried out separately for placebo and treatment groups. Results: LDL level was inversely related to overall mortality (p = 0.0105) and non-cardiovascular mortality (p = 0.0171) in the treatment group. By contrast, in the placebo group only non-cardiovascular mortality was inversely correlated to LDL (p = 0.0032). The regression lines have similar slopes and run almost parallel to each other, with the treatment line lying below the placebo line. To identify the threshold of risk for starting statin therapy, we analysed the relationship between baseline cardiovascular risk and overall mortality in the two groups. Both correlations are highly significant and regression lines intersect at a risk of 0.29% per year. This implies that the effects of statins are favourable when the baseline cardiovascular risk exceeds approximately 3% in 10 years. Conclusions: A trend of increased non-cardiovascular mortality with decreased LDL exists both in placebo and treatment groups. However, at each given LDL cholesterol level, non-cardiovascular mortality is lower in treated patients. Therefore, statin therapy may improve the biological impact of LDL on non-cardiovascular mortality.

Low-density lipoprotein cholesterol was inversely associated with 3-year all-cause mortality among Chinese oldest old: Data from the Chinese Longitudinal Healthy Longevity Survey

“…Second, epidemiological studies suggest that low LDL-C in the oldest old may exert an indirect effect to increase non-cardiovascular mortality [4]. It was not possible to establish a direct link of low LDL-C to an adverse effect on vascular mortality or non-vascular mortality because of the unavailable cause-specific mortality in our study.…”

“…First, studies of older populations have led to conflicting conclusions on the relationship between LDL-C and all-cause mortality. Some studies showed that high concentrations of LDL-C were associated with higher risk of mortality and morbidity of cardiovascular and cerebrovascular diseases or all-cause mortality among the elderly [2, 3], while other studies found that low LDL-C concentrations were associated with increased mortality risk from non-cardiovascular disease [4], such as cancer [5], infection [6], liver diseases [7], and trauma [8] among elderly. Several studies also concluded that LDL-C was inversely associated with the risk of death in elderly people [9–14], which has attracted particular attention regarding the necessity for LDL-C lowering therapy in the aged population.…”

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“…A recent meta-analysis reported that overall mortality was significantly lower in groups treated with a statin than placebo, independent of the statin lipid-lowering effect. 39 Several reports have also indicated that statins possess antioxidant effects that are thought to help reduce overall mortality. 40 We showed that statin treatment helped to decrease the free m1A level in CKD patients.…”

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“…Another study finds a trend of increased noncardiovascular mortality with decreased LDL, in both placebo and treatment groups (Razzolini et al 2008). However, at each given LDL cholesterol level, noncardiovascular mortality is lower in patients treated with statins (Razzolini et al 2008).…”

“…Conversely, studies of younger adults reveal that the effect of total cholesterol on noncardiovascular mortality is neutral (Kronmal et al 1993;Krumholz et al 1994;Gould et al 1995). Another study finds a trend of increased noncardiovascular mortality with decreased LDL, in both placebo and treatment groups (Razzolini et al 2008). However, at each given LDL cholesterol level, noncardiovascular mortality is lower in patients treated with statins (Razzolini et al 2008).…”