Additive Beneficial Effects of Fenofibrate Combined With Candesartan in the Treatment of Hypertriglyceridemic Hypertensive Patients

Abstract

OBJECTIVE -Mechanisms underlying fibric acid and angiotensin II type 1 receptor blocker therapies differ. Signaling from peroxisome proliferator-activated receptor ␣ may cross-talk with the angiotensin II system. We investigated vascular and metabolic responses to these therapies either alone or in combination in hypertriglyceridemic hypertensive patients.RESEARCH DESIGN AND METHODS -This was a randomized, double-blind, placebo-controlled, cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Forty-four patients were given 200 mg fenofibrate and placebo, 200 mg fenofibrate and 16 mg candesartan, or 16 mg candesartan and placebo daily during each treatment period.RESULTS -Fenofibrate, combined therapy, or candesartan therapy significantly reduced blood pressure. However, combined therapy significantly reduced blood pressure more than fenofibrate or candesartan alone (P Ͻ 0.001 by ANOVA). When compared with candesartan, fenofibrate or combined therapy significantly improved the lipoprotein profile. All three treatment arms significantly improved flow-mediated dilator response to hyperemia. Combined therapy significantly decreased plasma malondialdehyde, high-sensitivity C-reactive protein, and soluble CD40L levels relative to baseline measurements. Importantly, these parameters were changed to a greater extent with combined therapy when compared with monotherapy (P Ͻ 0.001, P ϭ 0.002, P ϭ 0.050, and P ϭ 0.032 by ANOVA, respectively). Fenofibrate, combined therapy, and candesartan significantly increased plasma adiponectin levels and insulin sensitivity relative to baseline measurements. However, the magnitude of these increases were not significantly different among the three therapies (P ϭ 0.246 and P ϭ 0.153 by ANOVA, respectively).CONCLUSIONS -Fenofibrate combined with candesartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy in hypertriglyceridemic hypertensive patients. Diabetes Care 29:195-201, 2006H ypertriglyceridemia and hypertension are major public health problems that are frequently treated with fenofibrate and angiotensin II type 1 receptor (AT 1 R) blockers (ARBs), respectively. Although the mechanisms of action for these two classes of drugs differ, both classes have beneficial effects on the vasculature. Large-scale clinical studies have demonstrated that micronized fenofibrate, fibric acid, and losartan, an ARB, prevent and retard the progression of coronary heart disease (1,2). Hypertension and coronary heart disease are frequently associated with insulin resistance and disorders of metabolic homeostasis such as obesity and type 2 diabetes. Endothelial dysfunction associated with cardiovascular diseases may contribute to insulin resistance and the pathophysiology of diabetes and its vascular complications (3). Indeed, large-scale clinical studies have demonstrated that candesartan reduces the onset of type 2 diabetes (4). The mechanisms of this benefit may relate to the ability of these therapies t...

Efonidipine Simultaneously Improves Blood Pressure, Endothelial Function, and Metabolic Parameters in Nondiabetic Patients With Hypertension

“…Assays for plasma insulin, malondialdehyde, adiponectin, leptin, and resistin were performed in duplicate by immunoradiometric assay or by enzymel i n k e d i m m u n o s o r b e n t a s s a y a s previously described (11)(12)(13). Quantitative insulin sensitivity check index (QUICKI) was calculated as described (14).…”

“…Quantitative insulin sensitivity check index (QUICKI) was calculated as described (14). Imaging studies of the right brachial artery were performed by ultrasound as described (11)(12)(13).…”

“…Quantitative insulin sensitivity check index (QUICKI) was calculated as described (14). Imaging studies of the right brachial artery were performed by ultrasound as described (11)(12)(13).Data are expressed as means Ϯ SEM or median (range 25-75%). We used paired Student's t test or Wilcoxon's signed-rank test to compare relative changes in response to treatment.…”

Does Fenofibrate Lower Blood Pressure?

“…Indeed, we first reported that fenofibrate significantly reduced SBP by 3 mm Hg (P=0.007) and DBP by 3 mm Hg (P=0.033) after 2 months' administration in hypertriglyceridemic, hypertensive patients when compared with baseline SBP 142 and DBP 90 mm Hg. 2 In a different study of ours in patients with primary hypertriglyceridemia, 3 fenofibrate did not significantly reduce SBP and DBP. Ten among 46 patients were mildly hypertensive.…”

Combination Therapy for Treatment or Prevention of Atherosclerosis

“…Fenofibrate combined with candesartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy in hypertriglyceridemic, hypertensive patients. 6 Thus, there is a strong and growing scientific rationale for recommending a combination of PPAR-␣ or PPAR-␥ and angiotensin II type I receptor blockers to prevent atherosclerosis and coronary heart disease. 2 …”