Abstract
BackgroundThere is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); however, causal evidence, especially from the Chinese population, is lacking. Therefore, this study aims to estimate the causal association between variants in genes affecting Lp(a) concentrations and CVD in people of Han Chinese ethnicity.MethodsTwo-sample Mendelian randomization analysis was used to assess the causal effect of Lp(a) concentrations on the risk of CVD. Summary statistics for Lp(a) variants were obtained from 1256 individuals in the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei. Data on associations between single-nucleotide polymorphisms (SNPs) and CVD were obtained from recently published genome-wide association studies.ResultsThirteen SNPs associated with Lp(a) levels in the Han Chinese population were used as instrumental variables. Genetically elevated Lp(a) was inversely associated with the risk of atrial fibrillation [odds ratio (OR), 0.94; 95% confidence interval (95%CI), 0.901–0.987; P = 0.012)], the risk of arrhythmia (OR, 0.96; 95%CI, 0.941–0.990; P = 0.005), the left ventricular mass index (OR, 0.97; 95%CI, 0.949–1.000; P = 0.048), and the left ventricular internal dimension in diastole (OR, 0.97; 95%CI, 0.950–0.997; P = 0.028) according to the inverse-variance weighted method. No significant association was observed for congestive heart failure (OR, 0.99; 95% CI, 0.950–1.038; P = 0.766), ischemic stroke (OR, 1.01; 95%CI, 0.981–1.046; P = 0.422), and left ventricular internal dimension in systole (OR, 0.98; 95%CI, 0.960–1.009; P = 0.214).ConclusionsThis study provided evidence that genetically elevated Lp(a) was inversely associated with atrial fibrillation, arrhythmia, the left ventricular mass index and the left ventricular internal dimension in diastole, but not with congestive heart failure, ischemic stroke, and the left ventricular internal dimension in systole in the Han Chinese population. Further research is needed to identify the mechanism underlying these results and determine whether genetically elevated Lp(a) increases the risk of coronary heart disease or other CVD subtypes.
Highlights
There is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); causal evidence, especially from the Chinese population, is lacking
A study by Ooi EM and colleagues showed that the concentration of lipoprotein (a) [Lp(a)] is independently associated with angiographic extent and severity of coronary artery disease [5], a study by Rallidis LS and colleagues showed that high levels of Lp(a) are continuously and independently associated with an increased risk of acute coronary syndrome [6]; and a study by Verbeek R and colleagues showed that Lp(a) and lowdensity lipoprotein cholesterol are independently associated with CVD risk [7]
The results of an observational study showed that Lp(a) is an independent risk factor associated with the progression of intima-media thickness [10], while the results from Mendelian randomization (MR) did not support an effect of Lp(a) variants on carotid intima-media thickness [11]
Summary
There is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); causal evidence, especially from the Chinese population, is lacking. Considering the limitations of observational studies, several studies have attempted to use MR to assess the relationship between Lp(a) and CVD: Yuesong Pan and colleagues found that Lp(a) concentrations were causally associated with an increased risk of large artery stroke but a decreased risk of small vessel stroke among European individuals [12]; Helgadottir S and colleagues showed that high Lp(a) concentrations were a cause of myocardial infarction and ischemic heart disease [13]; available evidence from genetic studies supports a causal role of Lp(a) and CVD, mainly including coronary heart disease, peripheral arterial disease, aortic valve stenosis and ischemic stroke [14] These MR studies were performed in populations such as Europeans, African-Americans, and residents of Copenhagen, while limited results are available for the Chinese population. The present study aimed to use two-sample MR to comprehensively evaluate the causal association between variants in genes affecting Lp(a) concentrations and CVD in East Asian populations
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