Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality, and a powerful predictor of adverse cardiovascular outcomes in the hypertensive patients. It has complex multifactorial and polygenic basis for its pathogenesis. We hypothesized that rare copy number variants (CNVs) contribute to the LVH pathogenesis in hypertensive patients. Copy number variants (CNV) were identified in 258 hypertensive patients, 95 of whom had LVH, after genotyping with a high resolution SNP array. Following stringent filtering criteria, we identified 208 rare, or private CNVs that were only present in our patients with hypertension related LVH. Preliminary findings from Gene Ontology and pathway analysis of this study confirmed the involvement of the genes known to be functionally involved in cardiac development and phenotypes, in line with previously reported transcriptomic studies. Network enrichment analyses suggested that the gene-set was, directly or indirectly, involved in the transcription factors regulating the “foetal cardiac gene programme” which triggered the hypertrophic cascade, confirming previous reports. These findings suggest that multiple, individually rare copy number variants altering genes may contribute to the pathogenesis of hypertension-related LVH. In summary, we have provided further supporting evidence that rare CNV could potentially impact this common and complex disease susceptibility with lower heritability.

Left Ventricular Hypertrophy (LVH) is a risk for various cardiovascular events among those with hypertension (HT). However the prevalence of hypertension-related LVH (HT LVH+) in communities with lower socioeconomic status (SES) is not adequately reported. This study investigated the prevalence of HT LVH+ among the urban and rural males and the attributing factors. A total of 1,923 males who had echocardiographic examinations done were recruited. Their blood pressure was measured to diagnose those with or without hypertension. Left ventricular mass index was determined. Univariate analysis was performed to identify associated factors predisposing to LVH. A total of 992 males had HT, of which 264 had LVH, and were more prevalent in older age groups and Malays (p<0.001). Individuals from rural areas, with low income and low educational background were associated with higher LVH prevalence (p<0.001). Those with moderate aortic regurgitation was 3.17-fold higher in LVH. Ninety-nine normotensives had LVH, 71.7% came from rural. Total cholesterol and low density lipoprotein cholesterol levels were significantly higher in HT LVH+ from urban than the rural areas (p=0.029 and p=0.002, respectively). A quarter of the HT population in Malaysia develop LVH, majority of them were from rural, indicating that socioeconomic disparities contribute to the higher risk of HT LVH+. The rural populations may have attributed to different risk factors as opposed to those from urban, hence emphasize the need to deliver targeted strategies for prevention and management HT LVH+ by different SES.

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