Research Highlight

Heart drug could risk heart

Subhra Priyadarshini

doi:10.1038/nindia.2008.145 Published online 17 March 2008

Madhu Khullar (centre) with her research team

Hydrochlorothiazide, an ingredient of many antihypertensive drugs, could increase the levels of a particular amino acid in blood called homocysteine, which has been linked to increased risk of heart disease, hypertension and stroke, new research suggests .

Working on a number of antihypertensive drugs such as ACE inhibitors, calcium channel blockers, β-blockers and hydrochlorothiazide diuretics, a team from the Postgraduate Institute of Medical Education and Research in Chandigarh found that patients on hydrochlorothiazide (25mg per day) showed increase in the Hcy levels.

Increased blood levels of the amino acid homocysteine (Hcy) have been linked to heart conditions even among people who have normal cholesterol levels. Even a small increase of five micromol per litre (5 μmol/L) of Hcy has been found to be associated with moderately increased risk of these diseases. Recent research shows that a number of drugs frequently given to patients of hypertension and heart disease might also have an influence on blood Hcy concentration.

"We examined the effect of commonly used antihypertensive drugs on plasma Hcy levels in essential hypertensive patients. With ACE inhibitors (ramipril, 5mg per day) or β -blockers (atenolol, 50 mg per day) for 6 weeks, we recorded a decrease in blood Hcy levels, whereas patients on hydrochlorothiazide (25mg per day) showed increase in the Hcy levels," says lead researcher Madhu Khullar.

The team did not find any change in Hcy levels in hypertensive patients on calcium channel blockers (amlodipine 5mg per day).

Khullar says that the significance of Hcy elevation is not clear at the moment. It might be clinically relevant if increase in Hcy levels increases the risk of cardiovascular disease and opposes the desired cardiovascular protection that comes with low blood pressure.

"However, the relative risks for cardiovascular events associated with an increase of Hcy are generally modest. Moreover, Hcy levels can be reduced, by the addition of vitamin supplementations such as folic acid, vitamin B12 and B6," she points out.

The findings need replication in a larger population of hypertensive individuals. At present, discontinuing treatment with thiazide diuretics because of their adverse effects on Hcy concentration might not be fully justified. "Physicians and relatives, however, should be informed about the possibility of the the influence of these drugs on Hcy levels," she says.


  1. Poduri, A. et al. Effect of ACE inhibitors and -blockers on homocysteine levels in essential hypertension. J. Hum. Hypertens. 22, 289-294 (2008)