Iatrogenic hyperhomocysteinemia in patients with metabolic syndrome: A systematic review and metaanalysis

Metabolic syndrome (MetS) is associated with increased cardiovascular mortality and its management incorporates hypolipidemic, antidiabetic and antihypertensive drugs. However, several classes of these drugs, such as biguanides, fibrates and hydrochlorothiazide have been reported to raise circulating total homocysteine (tHcy) levels. During the last decades, numerous large-scale epidemiological studies have identified Hcy as a moderate independent cardiovascular risk factor. Therefore, drug-induced hyperhomocysteinemia in MetS patients may add one cardiovascular risk factor in these high-risk patients. The present systematic review summarizes data from studies which investigated the effects of the above-mentioned drugs on tHcy, and calculates the treatment effect of each drug class on tHcy levels. We also discuss the underlying pathophysiology and the issues that should be addressed in the future.