Homocysteine predicts vascular target organ damage in hypertension and may serve as guidance for first-line antihypertensive therapy

Type of funding sources: Foundation. Main funding source(s): the primary author is supported by the Australian National Heart Foundation post docctoral fellowship

Dobney Hypertension Centre

Homocysteine is an independent risk factor for cardiovascular and cerebrovascular disease and has been proposed to contribute to vascular dysfunction. We sought to determine in a real-world clinical setting whether homocysteine levels were associated with hypertension mediated organ damage (HMOD) and could guide treatment choices in hypertension.

We performed a cross-sectional analysis of prospectively collected data in 145 hypertensive patients referred to our tertiary hypertension clinic at our Hospital and analysed the association of homocysteine with HMOD, renin-angiotensin-aldosterone signaling (RAAS) and blockade.

 The average age of participants was 56 ± 17 years and there was a greater proportion of males than females (89vs56). Regression analysis showed that homocysteine was significantly associated with PWV (β=1.99; 95% CI 0.99-3.0; p < 0.001), albumin creatinine ratio (β=1.14; 95% CI 0.47,1.8;  p < 0.001), 24 hr urinary protein excretion (β=0.7; 95% CI 0.48, 0.92; p < 0.001) and estimated glomerular filtration rate (β=-29.4;  95% CI -36.35, -22.4; p < 0.001), which persisted after adjusting for potential confounders such as age, sex, 24 hr BP, inflammation, smoking, diabetes mellitus, renal insufficiency and dyslipidaemia. A positive predictive relationship was observed between plasma homocysteine levels and PWV, with every 1.0 µmol/L increase in homocysteine associated with a 0.1 m/s increase in PWV. Homocysteine was significantly associated with elevated aldosterone concentration (β=0.26; p < 0.001), thereby possible RAAS activation, an effect better resisted by angiotensin receptor blockers than ACE-inhibitors in higher physiological ranges of homocysteine.

Our results indicate that homocysteine is associated with hypertension mediated vascular damage and could potentially serve to guide first-line antihypertensive therapy.