Genetic variants that confer lifelong low-density lipoprotein cholesterol (LDL-C) differences show a weaker effect on ischemic stroke (IS) than on coronary heart disease (CHD), according to study results published in Neurology.
Ischemic stroke comprises 70% to 90% of all strokes, and different IS subtypes have distinct underlying pathologies, including hypertension, dyslipidemia, and genetic determinants. Randomized studies have shown that lowering LDL-C reduces the risk for both IS and CHD, whereas observational studies have demonstrated stronger effects of LDL-C on CHD than on IS.
Therefore, using a 2-sample Mendelian randomization approach, researchers examined the causal relevance of lifelong differences in LDL-C for IS relative to that for CHD. They used information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels to estimate the causal effects of LDL-C for IS and IS subtypes (according to 12,389 IS cases) and for CHD (according to 60,801 cases).
The researchers found that a 1-mmol/L higher genetically determined LDL-C was associated with a 50% higher risk for CHD (P =1.1 × 10−8) whereas the causal effect of LDL-C was much weaker for IS (P =.14) and, in particular, for cardioembolic stroke (P =.64) when compared with that for CHD.
“This study suggests that LDL-C has a substantially weaker causal effect on IS than for CHD, a result that has potential implications for evaluation and development of therapeutic approaches,” concluded the authors.
They added that, “Additional large-scale genetic studies of IS, particularly with regard to specific IS subtypes and diverse ethnic populations, are needed to further elucidate these relationships.”
Valdes-Marquez E, Parish S, Clarke R, Stari T, Worrall BB, Hopewell JC. Relative effects of LDL-C on ischemic stroke and coronary disease. A Mendelian randomization study. Neurology. 2019;92:e1-e12.