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Drugs acting on cardiovascular (CV) prevention are, by definition, interconnected with age-induced arterial changes. However, this question has been poorly investigated along long-term treatment. This goal requires a major prerequisite: to determine statistical links associating age-induced changes in arterial stiffness and wave reflections with drug classes acting on CV prevention. We studied 347 subjects where CV prevention involved hypertension, diabetes mellitus and hypercholesterolaemia; and included six drug classes: diuretics, β-blocking agents, angiotensin II (ANGII) and calcium-channel (CCB) blockers, insulin therapy and statins. For each class, the total population was divided into two subgroups according to the presence or absence of the corresponding class. Statistical comparisons between subgroups involved brachial and central blood pressure measurements, aortic pulse wave velocity (PWV), augmentation index (AIx), used as a marker of wave reflections. Non-invasive measurements included tonometry and pulse wave analysis. Appropriate adjustments indicated among results the respective role of age, sex, mean blood pressure (MBP), standard risk factors and other confounding variables. CCB and statins did not exhibit statistical association with PWV or AIx. β-Blocking agents were significantly linked with heart rate reduction and resulting increase in AIx and central pulse pressure (PP). Increased PWV independent of age, MBP, CV risk factors were noticed under diuretics, ANGII blockers and insulin, pointing to intrinsic modifications of the arterial wall. Treatment of CV prevention involves alterations of the arterial wall depending on drug class. β-Blocking agents and insulin are associated with the higher increases of central PP.

Arterial stiffness is an independent predictor of cardiovascular events in a hypertensive population. Serum levels of matrix metalloproteinase (MMP)-9 are associated with arterial stiffness and predict cardiovascular risk. We investigated the role of MMP-9 polymorphism -1562CT on blood pressure (BP) and arterial stiffness in a newly diagnosed hypertensive population. Untreated hypertensive patients (n=215, mean age 46+/-13 years) were studied. Supine BP, carotid-femoral pulse wave velocity (PWV) and augmentation index were assessed. Serum biochemistry and plasma MMP-9 concentrations were measured and genotyping performed following extraction of genomic DNA. BP, aortic PWV and serum MMP-9 levels were significantly higher in T-allele carriers of the -1562CT polymorphism with a significant gene-dose effect (P0.0001). In a stepwise regression model adjusting for known or likely determinants, the 1562CT polymorphism emerged as an independent predictor of systolic BP (R(2)=0.25, P0.0001), diastolic BP (R(2)=0.16, P0.0001) and PWV (R(2)=0.47,P0.0001). This is the first study to show the effect of MMP-9 polymorphism on BP and aortic stiffness in a hypertensive population. These results suggest that hypertensive patients carrying the T allele may be at increased risk of cardiovascular events.

Although arterial stiffness is an independent cardiovascular risk factor associated with both aging and hypertension, relatively little is known regarding the structural changes in the vessel wall that occur with vessel stiffening. We determined if collagen type-I metabolism is related to arterial stiffening in both hypertensive and normotensive subjects. Arterial stiffness was assessed by aortic pulse wave velocity (PWV) and augmentation index (AIx) in 46 subjects (48.7 +/- 2 years, 32 hypertensives) and related to circulating markers of collagen type-I turnover. Collagen synthesis was assessed by the measurement of carboxy-terminal peptide of procollagen type-I (PIP) and collagen degradation by the measurement of carboxy-terminal telopeptide of collagen type-I (ICTP), by quantitative immunoassay. Matrix metalloproteinase-1 (MMP-1) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) were also quantified by immunoassay. The ratio of collagen type-I synthesis to degradation was negatively correlated with both PWV (P

Objective: Angiotensin-converting enzyme (ACE) inhibitors have beneficial effects on arterial compliance and distensibility and favourably modify the arterial pressure waveform in hypertensive patients. The objective of our study was to explore the possible effects of adding an ATII AT1 receptor antagonist to an ACE inhibitor on augmentation pressure, a measure of arterial stiffness, and pulse pressure amplification in patients with poorly controlled essential hypertension. Design and methods: We studied a group of 18 patients with poorly controlled hypertension, despite at least three antihypertensive drugs including an ACE inhibitor, before, at 2 h and 2 weeks following the administration of 80 mg of valsartan, an ATII AT1 receptor antagonist. Haemodynamic responses were measured by cuff sphygmomanometry, arterial pulse-wave analysis and the pulse pressure gradient was calculated as the difference between the brachial pulse pressure (cuff sphygmomanometry) and derived aortic pulse pressure (arterial pulse wave analysis). Results: Blood pressure decreased significantly (P < 0.001) and the effect was more pronounced on central (aortic) pulse pressure than peripheral (brachial) pulse pressure. the pulse pressure amplification increased significantly (from 8 ± 3 at baseline vs 12 ± 7 at 2 h to 14 ± 5 mm Hg at 2 weeks, P < 0.01) and the augmentation pressure decreased from a baseline value of 21 ± 8 to 11 ± 7 at 2 h and 10 ± 5 at 2 weeks, (P < 0.01) following valsartan. Conclusion: The results of our study show that in a group of poorly controlled hypertensives, combining an ATII AT1 receptor blocker to an ACE inhibitor induced a significant fall in blood pressure. The decrease in blood pressure was accompanied by a decrease in augmentation pressure in the ascending aorta with a greater decrease in the central pulse pressure than in the peripheral, favourably increasing pulse pressure amplification between central and peripheral arteries. This effect on arterial stiffness and amplification suggests that combined angiotensin II blockade by adding an AT1 receptor blocker to an ACE inhibitor may have more beneficial effects on the blood pressure curve than simple blood pressure reduction.

Influence of the G-protein β -3 subunit gene C825 T polymorphism on the clinical phenotype of newly diagnosed essential hypertension

As the effects of sildenafil are in part mediated by enhancing the action of nitric oxide and nitrates given acutely markedly reduce early wave reflection, we explored the effects of a single oral dose of sildenafil citrate (50 mg) on blood pressure and arterial wave reflection in treated hypertensive men in a single-blind randomised placebo controlled crossover study. Eight men (aged 57-76 years) with well controlled hypertension and erectile dysfunction and no contraindications to the use of sildenafil, were given either sildenafil 50 mg or placebo orally, with the second drug being given 2 weeks later. Blood pressure and heart rate with an automated digital oscillometric device (Omron) HEM-705 CP) and the augmentation index, a measure of arterial wave reflection in the aorta derived using radial applanation tonometry, were measured before and at 15-min intervals for 2 h thereafter. The extent of individual maximum reductions (mm Hg) from baseline in systolic (24 +/- 10 vs. 6 +/- 8, P < 0.05) and diastolic blood pressure (8 +/- 5 vs. 3 +/- 2, P < 0.05) occurred on the sildenafil study day. On average the brachial blood pressure at 75 min following sildenafil was 17/11 mm less than on the placebo day (P < 0.01). Augmentation index was also reduced significantly at 90 min (P < 0.05) suggesting reduced vascular tone in the arteries. The area under the brachial and aortic blood pressure and augmentation index time curve (by the trapezoidal rule corrected for baseline reading) was significantly lower (P < 0.05) on the sildenafil study day. The study shows that the peripheral vasodilatory effects of sildenafil, possibly related to nitric oxide, are accompanied by a fall in systemic blood pressure and reduced arterial wave reflection.