Effect of moxonidine and amlodipine on serum YKL-40, plasma lipids and insulin sensitivity in insulin-resistant hypertensive patients—a randomized, crossover trial

Abstract

Moxonidine is a selective imidazoline receptor agonist with comparable blood pressure-lowering efficacy to first-line antihypertensives and favorable metabolic effects. YKL-40 (chitinase-3-1-protein) has been proposed as a new marker of inflammation, atherosclerosis and endothelial dysfunction in neoplastic, cardiovascular and metabolic diseases but has not yet been studied in the context of essential hypertension. Fifteen patients (10 M, 5 F; age 48 ± 14 years) with arterial hypertension and insulin resistance (HOMA-IR index 42.77) on at least two antihypertensive drugs were randomized to receive either moxonidine (0.4 mg) or amlodipine (10 mg) for two 8-week periods with a 7-day wash-out. Serum insulin, glucose, C-reactive protein (CRP), lipids, uric acid, YKL-40 and blood pressure were measured and insulin sensitivity was calculated (HOMA) at the beginning and end of each study phase. Mean BP decreased significantly with both moxonidine and amlodipine (À9.8 ± 7.6 and À10.4 ± 7.3 mm Hg, respectively). Serum high-density lipoprotein cholesterol increased with both therapies, but only moxonidine-affected serum triglycerides. No significant changes in serum uric acid, CRP, YKL-40 (2.3 and 3.3 ng ml -1 , respectively) or HOMA index (0.70 ± 2.4 and 0.76 ± 2.8) were observed. There was a strong negative correlation between serum uric acid and YKL-40 concentration at baseline (r¼À0.77, P¼0.01). Serum YKL-40 did not correlate with blood pressure, biochemical parameters or HOMA index. Moxonidine is an effective adjunctive antihypertensive agent for use in patients with hypertension and insulin resistance that induces beneficial effects on serum lipid profile but does not reduce insulin resistance, inflammation or serum YKL-40 concentration.

Can YKL-40 be a new inflammatory biomarker in cardiovascular disease?

“…Therefore, it is important that a recent study in patients with hypertension and insulin resistance could not detect any changes in serum YKL-40 levels during an eight week anti-hypertensive therapy with moxonidine ® and amlodipine ® reducing mean blood pressure approximately 10 mm Hg (Masajtis-Zagajewska et al 2010). The influence of other medications on circulating YKL-40 level is not consistent between the studies.…”

Should the sympathetic nervous system be a target to improve cardiometabolic risk in obesity?

“…Insulin sensitivity was not improved by any of the treatments (34). Likewise, in patients who were insulin resistant with hypertension, moxonidine was found to have no effects on insulin resistance despite having beneficial effects on weight, high-density lipoprotein cholesterol, and triglycerides (102).…”

The Effects of Antihypertensive Agents in Metabolic Syndrome – Benefits Beyond Blood Pressure Control

“…In hypertensive patients with the metabolic syndrome, similar significant reductions in hsCRP and BP were seen with manidipine and amlodipine, but these data did not correlate with changes in other biomarkers, such as adiponectin, HOMA-IR, and TNF-, which showed greater improvements with manidipine than with amlodipine [122]. In a different study in patients with arterial hypertension and insulin resistance who were already receiving at least two antihypertensive agents, neither moxonidine nor amlodipine showed significant changes in hsCRP, whereas both treatments resulted in significant BP lowering [123].…”

“…Both treatments significantly lowered BP and increased HDL-C, but only moxonidine reduced serum triglycerides. Neither drug affected serum CRP levels [123].…”