Relative effects of LDL-C on ischemic stroke and coronary disease

Abstract

Objective To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. Methods We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. Results A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32−1.68, p = 1.1 × 10 −8 ). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96−1.30, p = 0.14; p for heterogeneity = 2.6 × 10 −3 ) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84−1.33, p = 0.64; p for heterogeneity = 8.6 × 10 −3 ) when compared with that for CHD. Conclusions In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.

Assessment of the Role of Carotid Atherosclerosis in the Association Between Major Cardiovascular Risk Factors and Ischemic Stroke Subtypes

“… 14 Complementing these observational associations, in findings from genetics consortia, genetically elevated LDL-C levels were associated with a higher risk of large artery stroke but not consistently with a risk of small artery stroke or cardioembolic stroke; however, more data are needed to reliably confirm these distinctions. 29 , 30 …”

Roles for circulating polyunsaturated fatty acids in ischemic stroke and modifiable factors: a Mendelian randomization study

“…In this study, we utilized this method to investigate the role between PUFA and IS. Additionally, lipids and blood pressure were the main modifiable factors of IS [4,[34][35][36][37]. So, we extended the objectives to these factors (LDL-C, HDL-C, TC, SBP and DBP).…”

Inverse Problem Algorithm Application to Semi-Quantitative Analysis of 272 Patients With Ischemic Stroke Symptoms: Carotid Stenosis Risk Assessment for Five Risk Factors

“…These findings contradict the results of Roy-O'Reilly et al, which claimed that either age or LDL-C factors dominated the carotid stenosis. [14][15][16] The IPA capability of integrating individual factors with their probable cross-interaction improved the program convergence and yielded a high value of r 2 ¼ 0:9352.…”

“…14 (2) LDL-C. Epidemiologists have reported that LDL-C level strongly promoted carotid stenosis in elderly patients with cerebral infarction. 15,16 (3) MAP. This is the mean pressure per one complete cardiac cycle in human arteries, which indicates the perfusion to organs more clearly than systolic or diastolic blood pressures (SBP and DBP, respectively: MAP ¼ ðSBP þ 2 Á DBPÞ=3.…”