cerivastatin and Hypertension

Hypertension and hypercholesterolemia are frequently associated, and their treatment is proven to reduce cardiovascular risk. Current guidelines on cardiovascular prevention strongly recommend treating both disorders. Unfortunately, the low treatment and control rates, combined with the high prevalence of both conditions, still contribute to the high burden of cardiovascular disease in Western countries. In the past 5 years, many studies evaluating the benefit of combined antihypertensive and lipid-lowering treatment on endothelial dysfunction, coronary atherosclerosis, hypertension control, and on primary and secondary prevention of cardiovascular events have been published. In this article, we discuss and critically evaluate the available evidence on the potential benefits of combined antihypertensive and lipid-lowering treatment.

Topics: Anticholesteremic Agents; Antihypertensive Agents; Arteriosclerosis; Cardiovascular Diseases; Comorbidity; Drug Therapy, Combination; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Nifedipine; Pyridines; Simvastatin

The objective of the study was to investigate the effects of cerivastatin therapy on forearm endothelial dependent acetylcholine (ACH) and independent (nitroprusside) vasodilator responses, blood pressure (BP) responses to intravenous infusions of angiotensin II (AII) and noradrenaline (NA) and on 24-h ambulatory BP recordings in type 2 diabetic men.. Eleven type 2 diabetic men aged 59 +/- 9 years with total cholesterol levels of 5.0 +/- 1.26 mmol/l, triglycerides of 2.23 mmol/l and high-density lipoprotein cholesterol levels of 1.24 mmol/l completed a double-blind, randomized, crossover trial comparing 8 weeks of cerivastatin therapy (800 microg of nocte) with placebo. Forearm vascular resistance (FVR) responses to intrabrachial-arterial infusions of ACH (3-24 microg/min), nitroprusside (2-16 microg/min), the nitric oxide(NO) synthase inhibitor l-nitro-mono-methyl arginine (l-nmma) (8 micromol/min), ACH during l-NMMA infusion and BP responses to intravenous infusions of AII (12.5-50 ng/min) and NA (20-400 ng/min) were measured at the end of each treatment period. Twenty-four-hour ambulatory BP recordings were also performed.. FVR responses to ACH during l-NMMA infusion were significantly (p = 0.026) greater during cerivastatin than during placebo therapy. In contrast, FVR responses to ACH in the absence of NO synthase inhibition did not differ significantly between cerivastatin and placebo therapies (p = 0.81). FVR increased by 31.4 +/- 57.3% in response to l-NMMA infusion during cerivastatin therapy compared with 6.1 +/- 41.2% during placebo therapy (p = 0.20). FVR responses to nitroprusside did not differ between cerivastatin and placebo therapies (p = 0.28), nor did BP responses to AII (systolic BP, p = 0.99; diastolic BP, p = 0.98) or NA (systolic BP, p = 0.21; diastolic BP, p = 0.48). Mean 24-h BP was similar during cerivastatin (123 +/- 10 or 70 +/- 7 mmHg) and placebo therapies (129 +/- 11 or 74 +/- 7 mmHg) (systolic BP, p = 0.26; diastolic BP, p = 0.41).. Cerivastatin increases FVR responses to ACH in type 2 diabetic men with mild dyslipidaemia but only following NO synthase inhibition. This may indicate an improvement in endothelium-derived hyperpolarizing factor-mediated responses.

Topics: Acetylcholine; Aged; Analysis of Variance; Angiotensin II; Blood Pressure Monitoring, Ambulatory; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Endothelium, Vascular; Forearm; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypertension; Infusions, Intravenous; Male; Middle Aged; Nitric Oxide Synthase; Nitroprusside; Norepinephrine; omega-N-Methylarginine; Pyridines; Vascular Resistance; Vasodilator Agents

Recent clinical studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert protective effects against nonhemorrhagic stroke. In a murine cerebral ischemia model produced by occlusion of the middle cerebral artery, statins were shown to reduce infarct size. However, the effect of statins on hypertension-based stroke is unknown. The purpose of this study is to clarify the effect of a statin on stroke in stroke-prone spontaneously hypertensive rats (SHR-SP), in which both cerebral hemorrhage and infarction occur.. We treated SHR-SP chronically from 4 weeks of age with cerivastatin (2 mg/kg per day by gavage) or vehicle. The physiological parameters, the incidence of stroke-associated symptoms, and mortality were assessed.. At 14 weeks of age, the incidence (13+/-3% versus 37+/-8%; P<0.01) and the size of stroke (1.6+/-0.2 versus 2.2+/-0.1 arbitrary units; P<0.01) were significantly decreased by cerivastatin, although blood pressure and plasma cholesterol levels were not different. Moreover, stroke-associated symptoms and early mortality of SHR-SP were markedly reduced in the statin-treated group (mortality at the age of 15 weeks: 15% versus 50%; P<0.05). Statin treatment significantly reduced superoxide production from nonstroke parenchyma of brain and infiltration of inflammatory cells to the stroke lesions.. Our data show that a high dose of statin exerts protection against hypertension-based stroke and ameliorates the disease severity via inhibition of superoxide production and modulation of inflammation in brain.

Topics: Animals; Blood Pressure; Blood Vessels; Brain; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Inflammation; Kinetics; Lipids; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Pyridines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stroke; Superoxides; Survival Analysis