ABSTRACT
Background@#and Purpose The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes. @*Methods@#Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH). @*Results@#Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001). @*Conclusions@#The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.
ABSTRACT
All the major lipid prevention guidelines agree that the 10-year risk of a cardiovascular event should be the primary method to select individuals for statin prevention of a cardiovascular event. They also all rely on LDL cholesterol (LDL-C) as the primary metric to monitor lipid lowering therapy. These two principles form the major instruments on which primary prevention of cardiovascular disease is based worldwide. Their application is based on decades of prospective observational studies and large numbers of randomized clinical trials. Their development and application are milestones in medical progress. But are there limits, which were unseen and unintended, that need to be identified and overcome so that cardiovascular prevention can improve? Based on new insights and old knowledge, this Viewpoint will apply Clinical Reasoning, the process by which we integrate all the relevant knowledge, including the knowledge we have gained from physiology, pathology, epidemiology, metabolism, experimental models of disease, and our clinical experience as well as the results of randomized clinical trials to the analysis of a single case to answer these questions. Moreover, this Viewpoint will challenge the universal practice of relating the clinical outcomes of the major successful lipid lowering trials to the decrease in LDL-C and argue that cardiovascular prevention should move from the Risk model to the Causal Benefit model. This Viewpoint will be framed around a single case because, as caregivers, we make decisions case by case and because, as caregivers, the individual is the true object of our concern.
