Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke

Abstract

BackgroundBlood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites for MI and stroke subtypes.ObjectivesThis study sought to investigate the associations of plasma metabolic markers with risks of incident MI, ischemic stroke (IS), and intracerebral hemorrhage (ICH).MethodsIn a nested case-control study (912 MI, 1,146 IS, and 1,138 ICH cases, and 1,466 common control subjects) 30 to 79 years of age in China Kadoorie Biobank, nuclear magnetic resonance spectroscopy measured 225 metabolic markers in baseline plasma samples. Logistic regression was used to estimate adjusted odds ratios (ORs) for a 1-SD higher metabolic marker.ResultsVery low-, intermediate-, and low-density lipoprotein particles were positively associated with MI and IS. High-density lipoprotein (HDL) particles were inversely associated with MI apart from small HDL. In contrast, no lipoprotein particles were associated with ICH. Cholesterol in large HDL was inversely associated with MI and IS (OR: 0.79 and 0.88, respectively), whereas cholesterol in small HDL was not (OR: 0.99 and 1.06, respectively). Triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI, with a similar pattern for IS. Glycoprotein acetyls, ketone bodies, glucose, and docosahexaenoic acid were associated with all 3 diseases. The 225 metabolic markers showed concordant associations between MI and IS, but not with ICH.ConclusionsLipoproteins and lipids showed similar associations with MI and IS, but not with ICH. Within HDL particles, cholesterol concentrations were inversely associated, whereas triglyceride concentrations were positively associated with MI. Glycoprotein acetyls and several non–lipid-related metabolites associated with all 3 diseases.

Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization

“…Future MR studies are needed to investigate this hypothesis. Our comprehensive examination of the associations of alcohol with lipid particles and lipid constituents replicated a recent metabolomic study 7 , and revealed that alcohol may increase large HDL-C particle size, total cholesterol concentration and apolipoprotein A1, which each are associated with reduced MI risk 15 ; however, when considering coincident increases in MI increasing constituents such as small and medium LDL-C and large LDL-C particle size 15 , and, as mentioned above, the RCTs and MR studies failing to find increased HDL-C and reduced CVD risk 8,[34][35][36] , further suggests any hypothetical cardioprotective mechanism derived from HDL-C metabolism changes may be further reduced when compared to assessments failing to consider these heterogenous associations. It is possible that alcohol consumption may reduce CHD risk through its modulation of HDL-C phospholipid content, which impacts reverse cholesterol transport 47 -a pathways inversely associated with prevalent CHD, even after controlling for HDL-C levels 48 -and has been shown to be reduced among CHD patients 47 .…”

“…Meta-analyses and short-term trials suggest alcohol consumption is associated with CVD risk factors including increased high-density lipoprotein-cholesterol (HDL-C) 13 ; however, the association with low-density lipoprotein cholesterol (LDL-C) and triglycerides (TRG) are less clear 14 . Variation in size, density, concentrations and composition of circulating lipids, which traditional measures are unable to distinguish, are thought to have contrasting effects to CVD risk 15 . Metabolomics provides a detailed view of systemic metabolism, and the physiological effect of alcohol consumption extends across multiple metabolic pathways 7 and has been associated with molecular dysregulation conferring both reduced and increased CVD risk 7 .…”

A detailed lipoprotein profile in relation to intima‐media thickness and echogenicity of three major arteries

“…It has previously been shown that the concentrations of small VLDL, IDL and all classes of LDL were related to carotid IMT, while large and medium size HDL were inversely related to IMT in this artery (Wurtz et al ., ). This lipoprotein profile is also seen in subjects developing a myocardial infarction or stroke in the future (Holmes et al ., ). This lipoprotein pattern is also found to be related to IMT in the carotid artery in the present study, as well as to IMT in the femoral artery, although the confidence intervals were much larger in the femoral artery.…”

Genetic variation in apolipoprotein A-I concentrations and risk of coronary artery disease

“…HDL cholesterol and apoA-I are among the serum lipoprotein measures showing strongest inverse associations with cardiovascular disease in epidemiological studies. 44,45 However, large phase III cardiovascular outcome RCTs using HDL cholesterol increasing therapies have failed to identify that the risk of CAD is proportionate to the amount by which HDL cholesterol is increased, 1, 2 and, consistently, studies of human genetics find that the association of HDL cholesterol with CAD is not causal. 5,6 In the REVEAL trial of the cholesteryl ester transfer protein (CETP) inhibitor, anacetrapib, although treatment with anacetrapib did increase HDL cholesterol, the cardiovascular benefit was proportionate to the degree of apoB lowering, rather than to the effect on HDL cholesterol.…”