JS-ECCR/HBPRCA-2: HOMOCYSTEINE AND LIPOPROTEIN (A) AS A DETERMINANT OF ARTERIAL STIFFNESS AND A PREDICTOR OF HYPERTENSION MEDIATED TARGET ORGAN DAMAGE (HMOD)

Abstract

Background: Despite advances in modern medicine, cardiovascular disease (CVD) remains a leading cause of global mortality. Among the many CVD determinants, hypertension is a leading modifiable risk factor and blood pressure control and prevention of hypertension mediated target organ damage (HMOD) has become the hallmark of cardiovascular risk management. Homocysteine and lipoprotein (a) are independent CVD risk factors, proposed to contribute to vascular compromise by facilitating thrombogenesis and atherosclerosis. Aims: We sought to determine in a real-world clinical setting whether these risk factors interact to facilitate vascular organ damage in hypertension. Methods: We performed a cross-sectional analysis of prospectively collected data in 131 hypertensive patients referred to our tertiary hypertension clinic at Royal Perth Hospital. The Lipoprotein (a), homocysteine and other biochemical parameters studied were assayed in the central hospital laboratory. We analysed the effect of the interaction between Lipoprotein (a) and homocysteine (Lpa-Hcy) on markers of HMOD including arterial stiffness, as assessed by pulse wave velocity (PWV). Results: The average age of participants was 56 ± 0.9 years, and there was a greater proportion of males than females (62% vs. 38%). The regression analysis demonstrated that Lp(a)-Hcy interaction was significantly associated with PWV [beta = 0.33; 95% CI 0.12, 0.55; p < 0.005], 24 h urinary protein excretion [beta = -10.9; 95% CI -14.5, -7.4; p < 0 .001], and estimated glomerular filtration rate [beta = 103.9; 95% CI 93.9, 113.8; p < 0.001], which persisted after adjusting for potential confounders such as age, sex, 24 h BP, inflammation, smoking, diabetes mellitus and other metabolic risk factors. Interaction analysis showed that increasing homocysteine and lipoprotein (a) concentration was associated with increasing arterial stiffness. Hcy levels does not affect the PWV if Lp(a) levels are normal and the knowledge of both Lp(a) and Hcy are necessary to determine arterial damage. Furthermore, Lp(a)-Hcy product exhibited a positive predictive relationship with every unit increase in Lp(a)-Hcy product associated with a 0.3 m/s increase in PWV which may represent a useful marker for cardiovascular risk stratification and may suggest the need for rigorous treatment to minimise HMOD progression. These clinical findings provide novel insights into the potential interaction between Lp(a) and Hcy in the pathogenesis of hypertension mediated vascular damage