Increased Cardiovascular Risks in Prehypertensives Expressing Angiotensin‑Converting Enzyme Gene Polymorphism
Background and Aim: Although angiotensin‑converting enzyme (ACE) gene polymorphism has been documented to play an important role in the genesis of hypertension, its role in the development of prehypertension has not been investigated. To study the association of ACE genotypes and their link to SVI and CV risks in young prehypertensives in Indian population. Methods: This cross‑sectional study was conducted in 172 individuals divided into prehypertensives (n = 57) and normotensives (n = 115) based on their level of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Body mass index, cardiovascular (CV) parameters such as heart rate (HR), SBP, DBP, mean arterial pressure (MAP), rate pressure product, stroke volume, left ventricular ejection time, cardiac output, total peripheral resistance, and baroreflex sensitivity (BRS) were recorded by continuous BP variability (BPV) monitoring using finapres, and sympathovagal imbalance (SVI) was assessed by spectral analysis of HR variability (HRV). Biochemical parameters such as homeostatic model assessment of insulin resistance (HOMA‑IR), lipid risk factors, inflammatory markers, renin and oxidative stress (OS) parameters were measured. Genotyping for ACE gene polymorphism (insertion [I]/deletion [D] or ID polymorphism) was done by polymerase chain reaction‑restriction fragment length polymorphism methods. Multiple regression analysis was done to assess the association between SVI and metabolic markers, and logistic regression was done to determine the BRS prediction of prehypertension status and CV risks in ACE genotypes. The BPV, HRV, and biochemical parameters were significantly altered in prehypertensives. Results: The ID genotype of ACE was most commonly distributed among the population (33.3% prehypertensives and 50.4% in normotensives). LH‑HF ratio, the marker of SVI, was significantly associated with MAP, HOMA‑IR, interleukin‑6, tumor necrosis factor‑alpha, renin, and BRS in ID genotype of prehypertensive population. BRS, the marker of CV risk, had significant prediction of prehypertension status in ID genotypes population. Conclusion: The ACE ID gene polymorphism appears to be the candidate gene for prehypertension. ID contributes to SVI in young prehypertensives attributed by insulin resistance and inflammation. The CV risks are strongly associated with prehypertension status in ID genotypes in prehypertensives.