Ravnskov Uffe, Diamond David M, Hama Rokura, Hamazaki Tomohito, Hammarskjöld Björn, Hynes Niamh, Kendrick Malcolm, Langsjoen Peter H, Malhotra Aseem, Mascitelli Luca, McCully Kilmer S, Ogushi Yoichi, Okuyama Harumi, Rosch Paul J, Schersten Tore, Sultan Sherif, Sundberg Ralf
Magle Stora Kyrkogata 9, 22350 Lund, Sweden.
Department of Psychology, Department of Molecular Pharmacology and Physiology, Center for Preclinical and Clinical Research on PTSD, University of South Florida, Tampa, Florida, USA.
BMJ Open. 2016 Jun 12;6(6):e010401. doi: 10.1136/bmjopen-2015-010401.
It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.
SETTING, PARTICIPANTS AND OUTCOME MEASURES: We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population.
We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found.
High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.
众所周知,随着年龄增长,总胆固醇对全因死亡率和心血管(CV)死亡率而言,其作为危险因素的作用减弱甚至不再构成危险因素,但对于总胆固醇的一个组成部分——低密度脂蛋白胆固醇(LDL-C)是否与老年人死亡率相关,却知之甚少,因此我们决定对此问题展开调查。
研究背景、参与者及结局指标:我们在PubMed上检索队列研究,这些研究将LDL-C作为≥60岁普通人群全因死亡率和/或CV死亡率的危险因素进行了调查。
我们确定了19项队列研究,包括30个队列,共计68094名老年人,其中28个队列记录了全因死亡率,9个队列记录了CV死亡率。在16个队列(14个具有统计学意义)中观察到全因死亡率与LDL-C之间存在负相关,这些队列占记录到这种关联的参与者总数的92%。在其余队列中,未发现关联。在两个队列中,最低LDL-C四分位数组的CV死亡率最高且具有统计学意义;在7个队列中,未发现关联。
在大多数60岁以上人群中,高LDL-C与死亡率呈负相关。这一发现与胆固醇假说(即胆固醇,尤其是LDL-C,本质上具有致动脉粥样硬化性)不一致。由于LDL-C水平高的老年人与LDL-C水平低的老年人寿命相当甚至更长,我们的分析为质疑胆固醇假说的有效性提供了理由。此外,我们的研究为重新评估将降低老年人LDL-C的药物治疗作为心血管疾病预防策略的一部分的指南提供了理论依据。