[Show abstract][Hide abstract] ABSTRACT: Increased heart rate (HR) is a risk factor for cardiovascular morbidity and mortality in the general population and in some clinical conditions. Endothelial dysfunction is an adverse prognostic factor for cardiovascular events. The aim of the study was to evaluate the effect of HR on central hemodynamic parameters and endothelial function in hypertension. We evaluated forearm blood flow (FBF) response to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) in 30 patients with HR ≤60 min(-1) and 30 with HR ≥80 min(-1). The FBF was measured by strain-gauge plethysmography. Transesophageal atrial pacing was used to increase the HR. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and correlate hemodynamic indices. The FBF response to ACh is lower in hypertensives with HR ≤60 min(-1) than in those with HR ≥80 min(-1) (10.6 ± 4.2 vs. 13.6 ± 5.1 ml × 100 ml(-1) of tissue × min(-1), P < 0.001). Vascular resistance decreases to 9.3 ± 2.8 U in patients with lower HR versus 7.2 ± 2.1 U in those with higher HR (P = 0.002). The FBF response to SNP is similar in both groups. Central systolic and pulse pressure are higher in bradycardic patients than in those with HR ≥80 min(-1) (140 ± 8 vs. 131 ± 8 mmHg, P = 0.0001 and 49 ± 10 vs. 39 ± 11 mmHg, P = 0.0001). All central hemodynamic parameters decrease during incremental atrial pacing. Augmentation index is the strongest predictor of endothelial dysfunction at multivariate analysis. These findings demonstrate that low HR affects endothelium-dependent vasodilation in hypertension. Increased central aortic pressure and hemodynamic correlates seem to be the underlying mechanisms by which bradycardia interferes with endothelium-dependent reactivity.
Internal and Emergency Medicine 05/2011; · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemoglobin (Hb) is an important nitric oxide (NO) buffer and a modulator of NO bioavailability. In addition, endothelial dysfunction is common in hypertensive patients, suggesting a pivotal role of hemoglobin concentration ([Hb]) in vascular function. To investigate the potential role of [Hb] in endothelium-dependent vasodilation, the relationship between Hb and endothelial function was tested in a group of patients with essential hypertension.
In this retrospective study, 174 nonsmoking, uncomplicated, never-treated hypertensives were enrolled. Endothelium-dependent and -independent vasodilation was assessed by measurement of forearm blood flow response during intra-arterial infusion of increasing doses of acetylcholine (ACh) and sodium nitroprusside (SNP) using strain-gauge plethysmography. Correlation with established risk factors of endothelial dysfunction was performed.
The vasodilatory response to ACh was inversely (P < 0.001) related to [Hb], and this relationship was dose dependent (P < 0.001), being minimal at the lowest dose and maximal at the highest dose. No association was found between Hb and the vasodilatory response to SNP. In a multiple linear regression model adjusted for Framingham risk factors (age, sex, BP, cholesterol, body mass index, glucose) and emerging risk factors (homeostasis model assessment index, C-reactive protein, estimated GFR), [Hb] maintained a strong and independent link with the vasodilatory response to ACh (P < 0.001).
In a large group of nonsmoking untreated hypertensives, [Hb] is inversely related to forearm endothelium-dependent vasodilation. [Hb] should be taken into account, especially in conditions associated with low [Hb], when performing vascular function studies.
Clinical Journal of the American Society of Nephrology 11/2010; 6(3):648-55. · 5.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Postmenopausal women have an increased risk of adverse cardiovascular (CV) events. Similarly, chronic kidney disease (CKD) is a well established risk factor for CV disease and mortality.
We evaluated the effect of renal function on the risk of death and CV events in 1500 southern Italian postmenopausal women.
Renal function was estimated (e) by glomerular filtration rate (e-GFR) by Modification of Diet in Renal Disease equation. We classified postmenopausal women in two groups of e-GFR (ml/min per 1.73 m(2)): > or =60 (group 1) and less than 60 (group 2). The primary endpoint was major adverse CV events (MACE). The secondary endpoints were total events (MACE + death from any cause), coronary events, and stroke. During the follow-up (mean=72.6 months), there were 200 new CV morbid events. The rate of MACE (per 100 patient-years) was 1.88 and 2.98 in the two groups of e-GFR (P<0.0001). On univariate analysis, the incident risk of CV events was inversely related with the e-GFR values; similarly, in multiple Cox regression model, only the e-GFR maintained an independent association with MACE and secondary end-points.
For the first time, we demonstrated that the reduction of e-GFR was associated with the increased risk of death and CV events, independently of traditional CV risk factors, menopause duration, and presence of metabolic syndrome.
European journal of cardiovascular prevention and rehabilitation: official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology 06/2009; 16(4):481-6. · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endothelial dysfunction and insulin resistance (IR) are associated with essential hypertension and other cardiovascular risk factors. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, induces endothelial dysfunction in different setting of patients. However, at this moment no data are available about the role of ADMA and IR to induce endothelial dysfunction in an independent way or combined between them. In this study, we investigated, in 63 hypertensives and 21 normotensive healthy subjects, the relationship between ADMA and IR and their possible interaction on endothelial function.
ADMA plasma levels were measured by high-performance liquid chromatography, and IR by homeostasis model assessment (HOMA). Endothelial function was estimated by intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside at increasing doses.
Hypertensive patients had significantly higher ADMA, insulin, HOMA and C-reactive protein (CRP) values than normotensive controls (P<0.0001). There were no significant differences in mean l-arginine/ADMA ratio between groups. ACh-stimulated forearm blood flow (FBF) was significantly reduced in hypertensive patients (P<0.0001). In hypertensive group, HOMA was the strongest determinant of FBF, accounting for the 45.5% of its variation. ADMA and gender were the independent determinants of HOMA, accounting for 12.3% and 8.3% of its variation, respectively.
The association between ADMA and IR contributes to identify a possible novel mechanism by which ADMA promotes vascular damage, increasing individual cardiovascular risk in hypertensive patients. However, this hypothesis should be tested in a larger study group.
International journal of cardiology 01/2009; 142(3):236-41. · 6.18 Impact Factor