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Biomedical subjects

Joseph A Vita

Publications and source records attributed to Joseph A Vita.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of improved left ventricular systolic function in an urban cardiomyopathy program.

After long-term therapy, some patients with systolic heart failure (HF) display improved left ventricular (LV) function over time, a response that is associated with improved long-term outcomes. To investigate predictors of improved LV function in an ethnically diverse HF cohort, we selected 71 patients with HF who had baseline ejection fractions (EF) <40%, follow-up EFs > or =50%, and >20% increases on follow-up echocardiography performed > or =6 months later. Their clinical features were compared with 142 age- and gender-matched control patients with baseline EFs <40% and no change or worse EFs on follow-up echocardiography. The baseline EFs were similar between patients and controls. Compared with controls, patients had a lower prevalence of diabetes mellitus (19.7% vs 36.6%, p = 0.01), a lower prevalence of an ischemic cause of disease (8.4% vs 35.2%, p <0.001), but a higher prevalence of a hypertensive cause of cardiomyopathy (29.6% vs 12%, p <0.001). Fewer patients than controls used aspirin (p = 0.04) or statins (p = 0.001) or had previous cardiac procedures (p = 0.009). In a multivariate conditional logistic regression model adjusting for age, gender, disease cause, statin use, cardiac procedures, change in heart rate, and follow-up time, hypertensive etiology was most strongly associated with improved LV function (adjusted odds ratio 9.73, 95% confidence interval 1.44 to 52.76, p = 0.02). In conclusion, patients with hypertensive causes of HF are more likely to demonstrate improved LV function over time than patients with ischemic causes of HF. Because long-term prognosis and indication for defibrillator implantation may be affected by changes in LV function, the present study provides additional support for the importance of evaluating the cause of HF to guide management.

Cardiomyopathies↗
PubMed2006

Endothelial function in HIV-infected persons.

BACKGROUND: Several reports have suggested an increased risk of coronary disease in human immunodeficiency virus (HIV)-infected patients receiving protease inhibitors (PIs). Impaired endothelium-dependent vasodilation is a putative surrogate marker of coronary atherosclerotic disease. METHODS: The present study evaluated the effect of HIV infection and antiretroviral treatment on endothelial vasomotor function, by assessing brachial artery flow-mediated dilation (FMD). A total of 75 HIV-infected patients were compared with 223 control subjects who were presumed to be HIV uninfected. RESULTS: HIV-infected patients had significantly impaired FMD, compared with control subjects (mean +/- SD, 7.3% +/- 4.4% vs. 11.1% +/- 6.3%; P < .0001). When adjustments were made for smoking status, sex, and body mass index, the difference between the 2 groups remained statistically significant (P < .01). In a cross-sectional analysis of the HIV-infected patients, we found significant associations between FMD and current injection drug use, hazardous drinking, HIV load, and alpha-high-density lipoprotein triglyceride levels, but not PI therapy. In a multivariate analysis, only current injection drug use and a lower alpha-high-density lipoprotein triglyceride level were significantly associated with FMD. CONCLUSIONS: HIV-infected patients have significant impairment of endothelial function, and this impairment is worse among those with elevated levels of HIV replication, particularly injection drug users.

Adult↗
PubMed2006

Cross-sectional relations of multiple biomarkers from distinct biological pathways to brachial artery endothelial function.

BACKGROUND: Endothelial dysfunction is a critical intermediate phenotype in the pathogenesis of cardiovascular disease. We evaluated the relative contributions of distinct biological pathways to interindividual variation in endothelial function by relating prototype biomarkers (representing these pathways) to brachial artery vasodilator function. METHODS AND RESULTS: We investigated the cross-sectional relations of a panel of 7 biomarkers measured at a routine examination to brachial artery vasodilator function (flow-mediated dilation [FMD] and reactive hyperemia) assessed at a subsequent examination (mean interval, 2.9 years) in 2113 Framingham Heart Study participants (mean age, 61 years; 54% women). We selected biomarkers from 4 biological domains: neurohormonal (N-terminal pro-atrial natriuretic peptide [N-ANP], B-type natriuretic peptide [BNP], renin, aldosterone), hemostatic factors (plasminogen activator inhibitor-1 [PAI-1]), inflammation (C-reactive protein [CRP]), and target organ damage (urine albumin-creatinine ratio). In age- and sex-adjusted models, several biomarkers were related to baseline brachial artery diameter (PAI-1, CRP, urine albumin-creatinine ratio), baseline mean flow (N-ANP, BNP, PAI-1, CRP, aldosterone), FMD (N-ANP, PAI-1, CRP, renin), and reactive hyperemia (BNP, PAI-1, CRP, renin, urine albumin-creatinine ratio). In multivariable analyses relating the 7 biomarkers conjointly to each vascular function measure (adjusting for known risk factors), N-ANP and renin were positively related to FMD (P=0.001 and P=0.04, respectively), and N-ANP was inversely related to baseline mean flow velocity (P=0.01). None of the other biomarkers was significantly related to the vascular function measures studied. CONCLUSIONS: In our large community-based sample, a conservative strategy relating several biomarkers to vascular endothelial function identified plasma N-ANP as a key correlate of mean flow under basal conditions and of FMD in response to forearm cuff occlusion.

Aged↗
PubMed2006

Endoscopic versus conventional radial artery harvest for coronary artery bypass grafting: functional and histologic assessment of the conduit.

BACKGROUND: The radial artery's propensity for vasospasm and vulnerability to surgical trauma are well known. A less invasive endoscopic method to harvest the radial artery was recently introduced, but its effect on radial artery integrity is unknown. METHODS: To compare the effects of harvest method on radial artery function, we prospectively randomized 54 patients undergoing coronary artery bypass grafting with the radial artery into 3 groups on the basis of harvest techniques: endoscopic, conventional with cautery, and conventional with harmonic scalpel. We assessed endothelium-dependent and endothelium-independent relaxation of radial artery segments to sequential doses of acetylcholine and nitroglycerin, respectively, using standard organ-chamber methodology. Vasospasm was assessed as the vasoconstrictor response to the thromboxane analog U46619. We assessed endothelial integrity using light and electron microscopy and by rating intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and P-selectin expression by means of immunohistochemistry on a semiquantitative 0- to 3-point scale. Harvest procedures were performed by a single surgeon, and data analyses were blinded to the harvesting method. RESULTS: Maximal relaxation-contraction responses to acetylcholine, nitroglycerin, and U46619 and effective drug concentration yielding 50% response were similar in the 3 groups. Adhesion molecule expression and histologic changes, as assessed by means of light and electron microscopy, were similar in the 3 groups. CONCLUSIONS: Endoscopic harvest does not alter radial artery vasoreactivity or endothelial integrity compared with conventional harvest techniques. Because the endoscopic technique is less invasive, it might prove to be the technique of choice to harvest the radial artery.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2006

The relationship between aldosterone, oxidative stress, and inflammation in chronic, stable human heart failure.

BACKGROUND: Aldosterone antagonists reduce morbidity and mortality in patients with severe heart failure, but the mechanisms responsible are not fully understood. Observations in animal models suggest that elevated levels of aldosterone promote oxidative stress and inflammation in the myocardium. It is unknown if these findings are relevant to heart failure patients who may have much lower aldosterone levels. METHODS AND RESULTS: We therefore examined the relationship of plasma aldosterone levels to markers of oxidative stress, inflammation and matrix turnover in 58 patients with chronic, stable heart failure from systolic dysfunction (LV ejection fraction <0.40) who were not receiving aldosterone antagonists. Chronic, stable heart failure patients had modestly elevated levels of aldosterone. Additionally, these patients had elevated levels of 8-isoprostaglandin F(2alpha), C-reactive protein, soluble intercellular adhesion molecule-1, osteopontin, brain natriuretic peptide, procollagen type III aminoterminal peptide, and tissue inhibitor of metalloproteinase-1. Among these patients with heart failure, aldosterone levels correlated with 8-iso-PGF(2alpha) (P = .003), ICAM-1 (P = .008), and TIMP-1 (P = .006) after adjustment for age, gender, race, diabetes, smoking, heart rate, left ventricular mass, and body mass index. CONCLUSION: In chronic, stable heart failure patients on standard therapy, higher aldosterone levels are associated with systemic evidence of oxidative stress, inflammation, and matrix turnover.

Aldosterone↗
PubMed2006

Effects of systemic inflammation on endothelium-dependent vasodilation.

The importance of inflammation in the pathogenesis of atherosclerosis is well established. The vascular endothelium contributes to and is affected by the inflammatory process. For example, a variety of cytokines have the ability to "activate" the endothelium and thereby promote expression of adhesion molecules and chemotactic factors that accelerate the inflammatory process and direct accumulation of leukocytes to specific sites in the arterial tree. In experimental systems, activation of endothelial cells is also associated with a loss of the biologic activity of endothelium-derived nitric oxide, an effect that accelerates the inflammatory process and also promotes local thrombosis and impairs local control of vasomotor tone. Consistent with these experimental studies, recent studies have provided evidence that inflammation is associated with an impairment of nitric oxide-dependent responses in human subjects. This article will review the experimental and clinical studies that support the relevance of inflammation to nitric oxide bioactivity in human atherosclerosis.

Atherosclerosis↗
PubMed2005

Cross-sectional relations of peripheral microvascular function, cardiovascular disease risk factors, and aortic stiffness: the Framingham Heart Study.

BACKGROUND: Aortic stiffness and small-artery structure and function share various risk factors; however, relations between these 2 measures of vascular function are complex and incompletely understood. METHODS AND RESULTS: We examined hyperemic forearm blood flow, an indicator of microvascular structure and function, and aortic stiffness in 2045 participants (1107 women, mean age 61+/-9 years) in the Framingham Heart Study offspring cohort. Using arterial tonometry, we evaluated 3 measures of aortic stiffness: brachial pulse pressure; carotid-femoral pulse wave velocity (CFPWV), which is related directly to aortic wall stiffness; and forward pressure wave amplitude (Pf), which is related directly to aortic wall stiffness and inversely to aortic diameter. Using high-resolution ultrasound and Doppler, we evaluated brachial artery diameter, blood flow, and forearm vascular resistance (FVR) at baseline and during reactive hyperemia after 5 minutes of forearm ischemia. In multivariable models that adjusted for cardiovascular disease risk factors, local brachial pulse pressure, CFPWV, and Pf, considered separately, were associated with increased baseline and hyperemic FVR (P<0.001). In models that further adjusted for mean arterial pressure, each measure of aortic stiffness was associated with reduced hyperemic flow (P<0.001). In risk factor-adjusted models that simultaneously considered CFPWV and Pf, both were associated with increased FVR at baseline (P<0.01) and during hyperemia (P<0.001). CONCLUSIONS: Our findings indicate that abnormal aortic stiffness and increased pressure pulsatility are associated with blunted microvascular reactivity to ischemic stress that is in excess of changes attributable to conventional cardiovascular disease risk factors alone, including mean arterial pressure.

Adult↗
PubMed2005

Low-renin hypertension with relative aldosterone excess is associated with impaired NO-mediated vasodilation.

Recent studies suggest that hypertension associated with low renin status and hyperaldosteronism is associated with increased risk for end-organ damage and cardiovascular events compared with other forms of hypertension. Additionally, experimental studies have demonstrated impaired nitric oxide-mediated bioactivity in these states. To investigate the relation between renin/aldosterone status and resistance vessel function, we examined plasma renin activity, serum aldosterone level, and forearm blood flow responses to the endothelium-dependent vasodilator methacholine and the endothelium-independent vasodilators sodium nitroprusside and verapamil using venous occlusion plethysmography in 130 volunteers (43 hypertensive, 87 normotensive). Low renin status was associated with impaired responses to methacholine and nitroprusside in patients with hypertension. Peak methacholine response was 8.7+/-5.6 mL/min per dL in the lowest renin quartile (0.1 to 0.3 ng/mL per hour) versus 14.3+/-7.3 mL/min per dL in the highest 3 renin quartiles combined (0.4 to 4.6 ng/mL per hour; P<0.001). Peak nitroprusside response was 5.6+/-2.3 mL/min per dL in the lowest renin quartile versus 13.3+/-4.1 mL/min per dL in the highest 3 renin quartiles combined (P<0.001). Blood pressure and other clinical characteristics were similar in all 4 quartiles. Vasodilator responses to verapamil did not relate to renin activity. Methacholine and nitroprusside responses did not relate to renin status in normotensive controls (P=0.34). Importantly, hypertensive patients with a high aldosterone/renin ratio also had impaired responses to methacholine. This study demonstrates that low-renin hypertension is associated with marked impairment of nitric oxide-mediated vasodilation of resistance vessels in the forearm vasculature of humans. This impairment could contribute to adverse outcomes in patients with low-renin hypertension and relative aldosterone excess.

Adult↗
PubMed2005

Common genetic variation at the endothelial nitric oxide synthase locus and relations to brachial artery vasodilator function in the community.

BACKGROUND: Sequence variants at the endothelial nitric oxide synthase (NOS3) locus have been associated with endothelial function measures, but replication has been limited. METHODS AND RESULTS: In reference pedigrees, we characterized linkage disequilibrium structure at the NOS3 locus using 33 common single nucleotide polymorphisms (SNPs). Eighteen SNPs that capture underlying common variation were genotyped in unrelated Framingham Heart Study participants (49.5% women; mean age, 62 years) with measured brachial artery flow-mediated dilation (n=1446) or hyperemic flow velocity (n=1043). Within 3 defined blocks of strong linkage disequilibrium that spanned NOS3, 11 SNPs captured >80% of common haplotypic variation. Among men, there were nominally significant associations between 8 NOS3 SNPs (minimum P=0.002) and between haplotypes (minimum P=0.002) and either flow-mediated dilation or hyperemic flow velocity. In women, we did not observe significant associations between NOS3 SNPs or haplotypes and endothelial function measures. To correct for multiple testing, we constructed 1000 bootstrapped null data sets and found that empirical probability values exceeded 0.05 for both phenotypes. CONCLUSIONS: A parsimonious set of SNPs captures common genetic variation at the NOS3 locus. A conservative interpretation of our results is that, accounting for multiple testing, we did not observe statistically significant relations between NOS3 sequence variants and endothelial function measures in either sex. The nominal associations of select NOS3 variants with endothelial function in men (unadjusted for multiple testing) should be viewed as hypothesis-generating observations and may merit testing in other cohorts and experimental designs.

Aged↗
PubMed2005

Heritability and a genome-wide linkage scan for arterial stiffness, wave reflection, and mean arterial pressure: the Framingham Heart Study.

BACKGROUND: Arterial stiffness and mean arterial pressure variably contribute to systolic hypertension and increased cardiovascular risk. However, few prior community-based studies have evaluated the genetics of arterial stiffness and separate mean and pulsatile components of blood pressure. METHODS AND RESULTS: Using arterial tonometry, we evaluated heritability and linkage of forward and reflected wave amplitude, mean arterial pressure, and carotid-femoral pulse wave velocity (CFPWV) in 1480 participants representing 817 pedigrees in the Framingham Study offspring cohort. In 204 families with tonometry data, a genome-wide scan was performed with microsatellite markers that covered the genome at 10-cM intervals. Heritability estimates were moderate for reflected wave amplitude (h2=0.48), forward wave amplitude (h2=0.21), CFPWV (h2=0.40), and mean arterial pressure (h2=0.33). Variance components linkage analysis identified 2 regions of linkage for reflected wave amplitude: chromosome 4 at 181 cM (logarithm of odds [LOD]=4.93, permuted P=0.002) and chromosome 8 at 33 cM (LOD=3.27, permuted P=0.058). There was 1 region of linkage for forward wave amplitude on chromosome 7 at 174 cM (LOD=2.88, permuted P=0.017). There were several regions of suggestive linkage for CFPWV: chromosome 2 at 94 cM (LOD=2.46), chromosome 7 at 29 cM (LOD=2.50), chromosome 13 at 108 cm (LOD=2.10), and chromosome 15 at 108 cM (LOD=2.48). There was 1 region of suggestive linkage for mean arterial pressure on chromosome 1 at 192 cM (LOD=2.18). CONCLUSIONS: Arterial stiffness measures and mean and pulsatile components of blood pressure are heritable and appear to have genetic determinants that may be linked to separate genetic loci in humans.

Aged↗
PubMed2005

Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: evidence for susceptibility loci on 1q.

Vascular inflammation plays a central role in atherosclerosis and inflammatory biomarkers predict risk of cardiovascular disease (CVD). Thus, finding genes that influence systemic levels of inflammatory biomarkers may provide insights into genetic determinants of vascular inflammation and CVD. We conducted variance-component linkage analyses of blood levels of four biomarkers of vascular inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1)] in 304 extended families from the Framingham Heart Study, using data from a 10cM genome scan. We computed p-values by a permutation approach. Heritability estimates ranged from 14% (IL-6) to 44% (MCP-1) after log transforming and adjusting for covariates. Significant linkage to MCP-1 was found on chromosome 1 (LOD=4.27 at 186cM; genome-wide p=0.005), in a region containing inflammatory candidate genes such as SELE, SELP (E- and P-selectin) and CRP. Other linkage peaks with LOD scores >2 were found for MCP-1 on chromosome 1 (LOD=2.04 at 16cM; LOD=2.34 at 70cM) and chromosome 17 (LOD=2.44 at 22cM) and for sICAM-1 on chromosome 1 at 229cM (LOD=2.09) less than 5cM from the interleukin-10 (IL10) gene. Multiple genes on chromosome 1 may influence inflammatory biomarker levels and may have a potential role in development of CVD.

Aged↗
PubMed2005

Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease.

We previously demonstrated that black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. To investigate potential mechanisms of this effect, we examined plasma catechins and systemic markers of oxidation, inflammation, and antioxidant protection from 66 subjects enrolled in that study. We collected samples at baseline, 2 h after 450 ml of black tea (acute), after 4 weeks of 900 ml of black tea per day (chronic), and after acute and chronic consumption of water. Total catechins increased 33% after acute tea (P < 0.05) and 29% after chronic tea (P < 0.05). Of individual catechins, plasma epicatechin gallate (ECG) concentration significantly increased with acute tea consumption, and plasma epicatechin (EC) increased with chronic tea consumption. Tea consumption did not improve plasma antioxidant capacity and did not reduce urinary 8-hydroxy-2'-deoxyguanosine, or urinary 8-isoprostane levels. Changes in catechin levels did not correlate with changes in endothelial function, plasma markers of oxidative stress, or C-reactive protein. In contrast, endothelial function at baseline correlated with dietary flavonoid intake (beta = 0.32, P = 0.02) and with baseline plasma EC concentration after adjusting for confounding variables (beta = 0.39, P = 0.03). These findings suggest that the benefits of black tea consumption on endothelial function may not be attributable to tea catechins or a systemic antioxidant or anti-inflammatory effect. Chronic dietary flavonoid status appears to relate to endothelial function, possibly suggesting that other flavonoids or polyphenolic components of tea favorably influence vascular health and risk for cardiovascular disease.

Catechin↗
PubMed2005

Effect of medical and surgical weight loss on endothelial vasomotor function in obese patients.

We prospectively examined brachial artery endothelial function using vascular ultrasound in 41 obese subjects treated with medical or surgical (gastric bypass) weight loss interventions. Surgical intervention produced greater weight loss and more pronounced improvement in endothelial function than medical treatment alone. Improved endothelial function with weight loss correlated strongly with fasting glucose but not with alteration in blood pressure, lipids, degree of weight loss, or plasma resistin concentrations. These data demonstrate that weight loss in markedly obese patients improves endothelial function and glycemic control that may represent important mechanisms of the cardiovascular benefit associated with weight reduction.

Adult↗
PubMed2005

Update on nitric oxide-dependent vasodilation in human subjects.

There currently is great interest in translating findings about the importance of nitric oxide (NO) in vascular biology to the clinical arena. The bioactivity of endothelium-derived NO can readily be assessed in human subjects as vasodilation of conduit arteries or increased flow, which reflects vasodilation of resistance vessels. This chapter provides an update on the available noninvasive methodology to assess endothelium-dependent vasodilation in human subjects.

Humans↗
PubMed2005

Polyphenols and cardiovascular disease: effects on endothelial and platelet function.

Epidemiologic studies suggest that higher polyphenol intake from fruits and vegetables is associated with decreased risk for cardiovascular disease. The mechanisms explaining this observation remain unclear. This review summarizes data suggesting that flavonoids improve endothelial function and inhibit platelet aggregation in humans. The vascular endothelium is a critical regulator of vascular homeostasis, and endothelial dysfunction contributes to the pathogenesis and clinical expression of coronary artery disease. Platelet aggregation is a central mechanism in the pathogenesis of acute coronary syndromes, including myocardial infarction and unstable angina. For these reasons, the observed effects of flavonoids on endothelial and platelet function might explain, in part, the observed beneficial effects of flavonoids on cardiovascular disease risk.

Blood Platelets↗
PubMed2004

Brachial artery vasodilator function and systemic inflammation in the Framingham Offspring Study.

BACKGROUND: In experimental studies, traditional risk factors and proinflammatory processes alter the regulatory functions of the vascular endothelium to promote atherosclerosis. These alterations include expression of leukocyte adhesion molecules and decreased bioavailability of endothelium-derived nitric oxide, an important regulator of vascular homeostasis and tone. The precise relations among risk factors, inflammation, and nitric oxide bioavailability remain uncertain. METHODS AND RESULTS: To test the hypothesis that inflammation impairs endothelial function in humans, we measured brachial artery flow-mediated dilation, reactive hyperemia, and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intracellular adhesion molecule-1 (sICAM-1), and monocyte chemotactic protein-1 (MCP-1) in 2701 participants from the Framingham Study (mean age 61 years, 53% women). There were modest unadjusted inverse correlations between flow-mediated dilation and CRP, IL-6, and sICAM-1 (P<0.001 for all) that were rendered nonsignificant after accounting for traditional coronary risk factors. For reactive hyperemia, we observed inverse correlations with markers of inflammation in unadjusted models that were attenuated 57% to 74% after accounting for risk factors. However, partial correlations of CRP, IL-6, and sICAM-1 with reactive hyperemia remained significant. CONCLUSIONS: Our observations are consistent with the hypothesis that risk factors induce a state of inflammation that impairs vascular function. For flow-mediated dilation, we found no evidence that inflammation has additional effects beyond those attributable to traditional risk factors. The incremental contribution of CRP, IL-6, and sICAM-1 to reactive hyperemia above and beyond known risk factors suggests that systemic inflammation may contribute to impaired vasomotor function in forearm microvessels.

Biomarkers↗
PubMed2004

Activation of endothelial nitric-oxide synthase by the p38 MAPK in response to black tea polyphenols.

Black tea improves endothelial function in patients with coronary artery disease. We sought to determine the responsible components of black tea and elucidate the underlying cell signaling mechanisms. We exposed porcine aortic endothelial cells to components of black tea and found that the polyphenol fraction acutely enhanced nitric oxide bioactivity. This effect involved endothelial nitric-oxide synthase (eNOS) phosphorylation at Ser-1177 and dephosphorylation at Thr-495, consistent with increased eNOS activity. These effects were calcium-dependent, as removal of extracellular calcium prevented eNOS phosphorylation at Ser-1177, whereas inhibition of intracellular calcium mobilization with TMB-8 blunted Thr-495 dephosphorylation. Black tea polyphenol-induced eNOS activation appeared dependent upon the phosphatidylinositol 3-kinase-Akt pathway, as it was significantly inhibited by LY294002 and a dominant negative Akt, respectively. Pharmacological inhibition of p38 mitogen-activated protein kinase (p38 MAPK) with either SB202190 or SB203580 as well as overexpression of a dominant negative p38 MAPKalpha attenuated both eNOS activation and phosphorylation changes in response to black tea polyphenols. Inhibition of p38 MAPKalpha also blunted Akt activation in response to black tea polyphenols, suggesting that p38alpha MAPK is upstream of Akt in this pathway. Finally, a constitutively active mutant of MKK6bE, an upstream kinase for p38 MAPK, enhanced both the basal and stimulated activity of Akt, leading to increased eNOS activity. Taken together, these data identify the p38 MAPK as an upstream component of Akt-mediated eNOS activation.

Adenoviridae↗