Physicians' Academy for Cardiovascular Education

Individuals at high genetic risk have greater benefit from statins

Polygenic Risk Score Identifies Subgroup with Higher Burden of Atherosclerosis and Greater Relative Benefit from Statin Therapy in the Primary Prevention Setting

Literature - Natarajan P, Young R, Stitziel NO, et al. - Circulation. 2017; CIRCULATIONAHA.116.024436


Statins lower relative risk by approximately 20% per 1.0 mmol/L of LDL-c. This is consistent across nearly all subgroups defined by clinical and biochemical measures [1,2], however two studies (ASCOT-LLA and JUPITER) recently reported that those at high genetic risk experienced greater relative risk reduction from statin therapy compared with all others [3,4]. This risk was defined by the 27-SNP polygenic risk score for coronary heart disease (CHD) [5].

Using WOSCOPS trial data, this study aimed to confirm this observation by an expanded 57-SNP polygenic risk score, as well as to assess whether the burden of subclinical coronary atherosclerosis is greater among those at high genetic risk. Genetic data were available in 4 892 men. Results from the ASCOT-LLA and JUPITER trial (6 978 and 8 769 individuals, respectively) were used for meta-analysis. The CARDIA and BioImage observational cohorts were used to explore the potential greater clinical benefit of statins in those at high genetic risk.

Main results


Although levels of LDL-c reduction were comparable, men with a high genetic risk derived a greater relative benefit from statin therapy. Furthermore, an expanded 57-SNP score was associated with subclinical atherosclerosis in two vascular beds. High genetic risk may identify individuals eligible to statins to prevent a first myocardial infarction event who otherwise would not be considered for treatment based on clinical criteria. This hypothesis can be tested in more contemporary cohorts with sizable proportions of statin-ineligible patients.


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