Risk reduction therapy for syndrome X: comparison of several treatments

Syndrome X, also termed the metabolic syndrome, is a cluster of physiologic and metabolic abnormalities including abdominal obesity, hyperinsulinemia, dyslipidemia and hypertension. Severe cardiovascular morbidity is associated with this pre-diabetic syndrome. We recently suggested that hyperhomocysteinemia is affiliated with this syndrome and thereby contributes to the vascular risk accompanying this condition. The present study compared the effects of antihypertensive, lipid-lowering, and insulin-sensitizing agents on the above-mentioned components of this metabolic syndrome.

Experimental metabolic syndrome was induced in Sprague-Dawley rats by feeding them a fructose-enriched diet (FED) for 5 weeks. During the last 2 weeks, the rats were treated with amlodipine, captopril, bezafibrate, or rosiglitazone in addition to FED. The control group did not receive any medication. Another control group was fed standard rat chow for 5 weeks. Post- and pretreatment measurements of body weight, systolic blood pressure (SBP), fasting plasma insulin, triglycerides, and total homocysteine concentrations were compared.

Amlodipine reduced SBP but did not show metabolic impact. Bezafibrate improved SBP, triglycerides, and insulin but induced elevation of homocysteine levels. Captopril and rosiglitazone remarkably improved SBP, insulin, triglycerides, and total homocysteine levels. In addition, rosiglitazone alone promoted weight gain.

The results indicate that captopril and rosiglitazone have a greater cardiovascular protective potential than amlodipine or bezafibrate. Captopril would be the best choice for patients with metabolic syndrome in whom hypertension and obesity are prominent, whereas rosiglitazone would be the preferred drug when glucose and other metabolic parameters are disturbed.