Mohammed A. Kashem

Relationship of visit-to-visit and ambulatory blood pressure variability to vascular function in African Americans.

Visit-to-visit clinic blood pressure variability (BPV) and 24-h BPV have both been identified as independent risk factors for cardiovascular (CV) morbidity and mortality; however, the mechanisms contributing to the increased CV risk as yet are unclear. The purpose of this study was to assess the relationship between BPV and endothelial function in a cohort of putatively healthy African Americans. A total of 36 African Americans who were sedentary, non-diabetic, non-smoking, free of CV and renal disease and not on antihypertensive medication followed an American Heart Association low fat, low salt diet for 6 weeks. Upon completion of the 6-week dietary stabilization period, participants underwent 24-h ambulatory BP monitoring and had their office blood pressure (BP) measured on 3 separate days. Right brachial artery diameter was assessed at rest, during reactive hyperemia (flow-mediated vasodilation: FMD), and after nitroglycerin administration (nitroglycerin-mediated vasodilation: NMD). Participants classified as having decreased endothelial function according to either %FMD or the FMD/NMD ratio had significantly higher 24-h BPV and a trend for higher visit-to-visit BPV when compared with participants with normal endothelial function. Continuous variable analyses revealed a significant positive association between NMD and 24-h diastolic BPV (DBPV). Visit-to-visit systolic BPV (SBPV), 24-h SBPV and 24-h DBPV were all negatively associated with the FMD/NMD ratio. All relationships remained significant after adjustment for age, body mass index and mean BP levels. These results may suggest that BPV is increased in African Americans with decreased endothelial function and is associated with the vascular smooth muscle response to nitric oxide.

A canine model of dilated cardiomyopathy induced by repetitive intracoronary doxorubicin administration

OBJECTIVE A simple and reproducible large animal model of dilated cardiomyopathy has yet to be developed. This study was performed to establish a canine model of dilated cardiomyopathy. METHODS Six closed-chest pure-bred beagles weighing 8 to 12 kg (10 +/- 1.9 kg) underwent intracoronary infusion of doxorubicin (Adriamycin). Low-dose (0.7 mg/kg) doxorubicin was infused into the left main coronary artery through a 5F Judkins catheter. Infusions were repeated weekly for 5 weeks. We evaluated the effects on cardiac hemodynamics, chamber size, the neuroendocrine system, and cardiac ultrastructure before and 1 and 3 months after five intracoronary infusions of doxorubicin. RESULTS Three months after treatment, fractional shortening (mean +/- standard error of the mean) had decreased from 36.5% +/- 0.8% to 21.7% +/- 1.4% (p = 0.0003), and left ventricular ejection fraction had decreased from 71.0% +/- 3.3% to 36.3% +/- 5.5% (p = 0.001). The left ventricular diastolic dimension had increased from 27.8 +/- 0.9 to 35.5 +/- 0.6 mm (p = 0.003), and the left ventricular end-diastolic volume had increased from 27.5 +/- 1.8 to 38.3 +/- 1.9 ml (p = 0.015). Left ventricular end-diastolic pressure had increased from 8.5 +/- 0.9 to 14.5 +/- 1.1 mm Hg (p = 0.01), and the stroke volume had decreased from 16.7 +/- 0.9 to 11.5 +/- 0.4 ml (p = 0.001). During the same period, the plasma norepinephrine concentration also increased from 114 +/- 27.4 to 423 +/- 88.9 pg/ml (p = 0.024), and plasma atrial natriuretic peptide levels increased from 33.8 +/- 7.0 to 76.5 +/- 14.8 pg/ml (p = 0.012). Histologic changes such as myofiber atrophy and cytoplasmic vacuolation, accompanied with interstitial fibrosis, were found predominantly in the left ventricle. CONCLUSION Repeated intracoronary infusions of doxorubicin represent a simple and reliable technique to produce dilated cardiomyopathy in the dog. This model can be used to evaluate the effects of new therapies, especially surgical treatments such as dynamic cardiomyoplasty and reduction ventriculoplasty, on dilated cardiomyopathy.

Endothelial activation microparticles and inflammation status improve with exercise training in African Americans

African Americans have the highest prevalence of hypertension in the world which may emanate from their predisposition to heightened endothelial inflammation. The purpose of this study was to determine the effects of a 6-month aerobic exercise training (AEXT) intervention on the inflammatory biomarkers interleukin-10 (IL-10), interleukin-6 (IL-6), and endothelial microparticle (EMP) CD62E+ and endothelial function assessed by flow-mediated dilation (FMD) in African Americans. A secondary purpose was to evaluate whether changes in IL-10, IL-6, or CD62E+ EMPs predicted the change in FMD following the 6-month AEXT intervention. A pre-post design was employed with baseline evaluation including office blood pressure, FMD, fasting blood sampling, and graded exercise testing. Participants engaged in 6 months of AEXT. Following the AEXT intervention, all baseline tests were repeated. FMD significantly increased, CD62E+ EMPs and IL-6 significantly decreased, and IL-10 increased but not significantly following AEXT. Changes in inflammatory biomarkers did not significantly predict the change in FMD. The change in VO2 max significantly predicted the change in IL-10. Based on these results, AEXT may be a viable, nonpharmacological method to improve inflammation status and endothelial function and thereby contribute to risk reduction for cardiovascular disease in African Americans.

Visit-to-visit and 24-h blood pressure variability: association with endothelial and smooth muscle function in African Americans

The purpose of this study was to investigate the association of visit-to-visit and 24-h blood pressure (BP) variability with markers of endothelial injury and vascular function. We recruited 72 African Americans who were non-diabetic, non-smoking and free of cardiovascular (CV) and renal disease. Office BP was measured at three visits and 24-h ambulatory BP monitoring was conducted to measure visit-to-visit and 24-h BP variability, respectively. The 5-min time-course of brachial artery flow-mediated dilation and nitroglycerin-mediated dilation were assessed as measures of endothelial and smooth muscle function. Fasted blood samples were analyzed for circulating endothelial microparticles (EMPs). Significantly lower CD31+CD42− EMPs were found in participants with high visit-to-visit systolic blood pressure (SBP) variability or high 24-h diastolic blood pressure (DBP) variability. Participants with high visit-to-visit DBP variability had significantly lower flow-mediated dilation and higher nitroglycerin-mediated dilation at multiple time-points. When analyzed as continuous variables, 24-h mean arterial pressure variability was inversely associated with CD62+ EMPs; visit-to-visit DBP variability was inversely associated with flow-mediated dilation normalized by smooth muscle function and was positively associated with nitroglycerin-mediated dilation; and 24-h DBP variability was positively associated with nitroglycerin-mediated dilation. All associations were independent of age, gender, body mass index and mean BP. In conclusion, in this cohort of African Americans visit-to-visit and 24-h BP variability were associated with measures of endothelial injury, endothelial function and smooth muscle function. These results suggest that BP variability may influence the pathogenesis of CV disease, in part, through influences on vascular health.

Managing hypertension in urban underserved subjects using telemedicine--a clinical trial.

BACKGROUND We evaluated an Internet- and telephone-based telemedicine system for reducing blood pressure (BP) in underserved subjects with hypertension. METHODS A total of 241 patients with systolic BP ≥140 mm Hg were randomized to usual care (C; n = 121) or telemedicine (T; n = 120). The T group reported BP, heart rate, weight, steps/day, and tobacco use twice weekly. The primary outcome was BP control at 6 months. RESULTS Average age was 59.6 years, average body mass index was 33.7 kg/m(2), 79% were female, 81% were African American, 15% were white, 53% were at or below the federal poverty level, 18% were smokers, and 32% had diabetes. Six-month follow-up was achieved in 206 subjects (C: 107, T: 99). Goal BP was achieved in 52.3% in C and 54.5% in T (P = .43). Systolic BP change (C: -13.9 mm Hg, T: -18.2; P = .118) was similar in both groups. Subjects in the T group reported BP 7.7 ± 6.9 d/mo. Results were not affected by age, sex, ethnicity, education, or income. In nondiabetic T subjects, goal BP was achieved in 58.2% compared with 45.2% of diabetic T subjects (P = .024). Nondiabetic T subjects demonstrated a greater reduction in systolic BP (T: -19 ± 20 mm Hg, C: -12 ± 19 mm Hg; P = .037). No difference in BP response between C and T was noted in patients with diabetes. CONCLUSION In hypertensive subjects, engagement in a system of care with or without telemedicine resulted in significant BP reduction. Telemedicine for nondiabetic patients resulted in a greater reduction in systolic BP compared with usual care. Telemedicine may be a useful tool for managing hypertension particularly among nondiabetic subjects.

Effects of Moderate Aerobic Exercise Training on Vascular Health and Blood Pressure in African Americans

As healthcare progresses toward individualized medicine, understanding how different racial groups respond to lifestyle interventions is valuable. It is established that African Americans have disproportionate levels of cardiovascular disease and impaired vascular health, and clinical practice guidelines suggest lifestyle interventions as the first line of treatment. Recently, the authors reported that 6 months of aerobic exercise improved inflammatory markers, flow‐mediated dilation (FMD), and levels of circulating endothelial microparticles (EMPs) in African American adults. This study is a subgroup analysis of the aerobic exercise–induced changes in vascular health and blood pressure (BP) measures, including carotid artery intima‐media thickness (IMT), nitroglycerin‐mediated dilation (NMD), ambulatory BP, and office BP. Sedentary African American adults (53.4±6.2 years; 21 women and 5 men) showed improved vascular health but no change in BP. Carotid artery IMT decreased 6.4%, plasma nitric oxide levels increased 76.6%, plasma EMP levels decreased, percentage of FMD increased 59.6%, and FMD/NMD ratio increased 36.2% (P<.05 for all). Six months of aerobic exercise training is sufficient to elicit improvements in vascular structure and function in African Americans, even without improvements in BP measures or NMD (ie, smooth muscle function). To our knowledge, this is the first study to report such findings in African Americans.

Hospitalized Acute Exacerbation of COPD Impairs Flow and Nitroglycerin-Mediated Peripheral Vascular Dilation

Vascular function, as measured by flow mediated dilation (FMD) and nitroglycerin mediated dilation (NMD), is impaired in COPD. Increases in systemic inflammatory mediators during acute exacerbations of COPD (AECOPD) may further impair vascular function and may account for the increased prevalence of cardiovascular disease in COPD patients. Similarly it may account for the increased morbidity and mortality in COPD patients hospitalized with acute exacerbations. We hypothesized that FMD and NMD would be impaired during AECOPD requiring hospitalization and that vascular function would improve upon AECOPD resolution. We used FMD and NMD to evaluate vascular function in 19 patients hospitalized with AECOPD. FMD and NMD were repeated approximately three months later in 8 of these patients. In these eight patients significant improvements were observed in FMD (2.6 ± 1.5% vs 5.1 ± 2.4%, p = 0.04) and NMD (5.0 ± 2.6% vs 13.3 ± 4.5, p = 0.02) after resolution of their exacerbation. We conclude that endothelial and vascular smooth muscle function is markedly impaired during AECOPD requiring hospitalization and improves following resolution. The systemic vascular impairment that occurs during AECOPD may partially explain the observed increased in cardiac morbidity and mortality that occur in this population.

A standardized exercise intervention differentially affects premenopausal and postmenopausal African-American women

ObjectiveAfrican-American women represent an understudied population in menopause research yet face greater postmenopausal challenges associated with mortality than their white peers. We investigated the effects of a mild-intensity aerobic exercise training program on markers of mortality risk in both premenopausal and postmenopausal African-American women. MethodsSixteen premenopausal women and 19 postmenopausal women underwent 6 months of mild-intensity aerobic exercise training. Measurements included markers of blood lipid and glucose profile, inflammation, kidney function, vascular health, and aerobic fitness before and after the exercise intervention. ResultsBefore the exercise intervention, the premenopausal and postmenopausal groups only differed in age, low-density lipoprotein, and total cholesterol levels, with the latter two being higher in the postmenopausal group. Both triglycerides and markers of early-stage endothelial dysfunction (CD62E+ endothelial microparticles) improved in both groups with aerobic exercise training. Aerobic fitness, glomerular filtration rate, body mass index, plasma glucose levels, and markers of late-stage endothelial dysfunction (CD31+/CD42b− endothelial microparticles) only improved in the premenopausal group. ConclusionsMild-intensity aerobic exercise training succeeds in improving some markers of cardiovascular disease and mortality in postmenopausal women. Higher levels of exercise intensity or perhaps additional interventions may need to be considered to further decrease mortality risk in this population.

Tricuspid valve reconstruction with the extracellular matrix tube technique: A word of caution

CLINICAL SUMMARY A 34-year-old woman, a current user of intravenous drugs, had development of tricuspid valve endocarditis with vegetations and severe regurgitation, along with multiple abscesses in her lungs. The patient underwent tricuspid valve surgery through a median sternotomy with standard bicaval cardiopulmonary bypass. At surgery, almost the entire tricuspid valve and the subvalvular apparatus were seen to have been destroyed and replaced with vegetations. The tricuspid annulus was measured at 50 mm. Two edges of a 10-cm CorMatrix ECM biomaterial patch were sewn together with 5-0 Prolene suture (Ethicon Inc, Somerville, NJ) in running fashion to create a tube 30 mm in diameter. Under aortic crossclamping, the entire