Razzolini Renato, Tarantini Giuseppe, Ossena Giovanni, Favaretto Enrico, Bilato Claudio, Manzato Enzo, Dalla-Volta Sergio, Iliceto Sabino
Department of Cardiology, University of Padova Medical School, Padova, Italy.
Cardiology. 2008;109(2):110-6. doi: 10.1159/000105551. Epub 2007 Aug 16.
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.
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.
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.
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.
截至目前，他汀类药物对非心血管疾病死亡率的影响仍存在争议。单项研究未能提供明确答案。我们对他汀类药物随机试验进行了荟萃回归分析，以提供证据证明非心血管疾病死亡率与他汀类药物治疗及低密度脂蛋白（LDL）胆固醇血浆水平相关。
我们选择了29项他汀类药物与安慰剂对比的随机对照试验，共90480例患者，随访时间超过12个月。记录基线和随访时的LDL水平以及全因死亡率、心血管疾病死亡率和非心血管疾病死亡率。分别对安慰剂组和治疗组进行加权线性回归分析。
治疗组中，LDL水平与总死亡率（p = 0.0105）和非心血管疾病死亡率（p = 0.0171）呈负相关。相比之下，在安慰剂组中，仅非心血管疾病死亡率与LDL呈负相关（p = 0.0032）。回归线斜率相似且几乎相互平行，治疗组的线位于安慰剂组的线下方。为确定开始他汀类药物治疗的风险阈值，我们分析了两组中基线心血管风险与总死亡率之间的关系。两种相关性均高度显著，回归线在每年0.29%的风险水平处相交。这意味着当基线心血管风险在10年内超过约3%时，他汀类药物的效果是有益的。
安慰剂组和治疗组均存在LDL降低时非心血管疾病死亡率增加的趋势。然而，在每个给定的LDL胆固醇水平上，治疗患者的非心血管疾病死亡率更低。因此，他汀类药物治疗可能会改善LDL对非心血管疾病死亡率的生物学影响。
