Inference of a causal relation between low-density lipoprotein cholesterol and hypertension using mendelian randomization analysis

Abstract

Background It is known in some studies that higher the LDL-C, the greater the risk of developing cardiovascular disease. However, studies of the causal effects between LDL-C and hypertension are limited by their observational study design, and genetic epidemiology studies of associations between LDL-C and hypertension are lacking, as are studies using data for Koreans. In this study, we confirmed the causal effect of LDL-C on hypertension using Korean chip data. Method The epidemiology and genotype data were collected from the Korean Genome and Epidemiology Study conducted by the Korea National Institute of Health and covered 20,701 subjects. Single-nucleotide polymorphisms associated with LDL-C were selected (p-value < 5 × 10− 8) from the Global Lipids Genetics Consortium database, and Mendelian randomization analysis (MRA) was performed with counted genetic risk scores and weighted genetic risk scores (WGRSs) for 24 single-nucleotide polymorphisms. Result The assumptions for MRA were statistically confirmed, and WGRSs showed a strong association with LDL-C. Interestingly, while the relationship between LDL-C and hypertension was not statistically significant in the observational study, MRA study demonstrated that the risk of hypertension increased as LDL-C increased in both men and women. Conclusions The results of this study confirmed that the relationship between LDL-C and hypertension is greatly influenced by genetic information.

Prevalence of a combination of hypertension and dyslipidemia among the adult population of a large East Siberian region

“…Тот же самый подход МР с применением метарегрессионного анализа убедительно показал, что длительное (пожизненное) генетически обусловленное снижение как ХС ЛНП, так и систолического артериального давления (АД), а в еще большей степени -их комбинация, приводят к значимому уменьшению сердечно-сосудистого риска [15]. Более того, появились первые данные в пользу того, что между уровнем ХС ЛНП и АГ может существовать причинно-следственная связь [16]. Неудивительно, что экспертами Европейского общества по атеросклерозу среди всех показателей липидного обмена именно ЛНП признаются важнейшим, "первичным драйвером атерогенеза" [17,18].…”