John Kwagyan

Association of Physical Activity Level and Stroke Outcomes in Men and Women: A Meta-Analysis

OBJECTIVE The protective effect of physical activity (PA) on risk of stroke remains controversial as a result of lack of insight into the sources of heterogeneity between studies. We performed a comprehensive meta-analysis of studies to (1) quantify the association between PA level and risk of stroke outcomes and (2) test the hypothesis that the association of PA level with stroke outcomes will be similar between men and women. The outcome measures are stroke incidence, stroke mortality, or both. METHODS Cohort studies were identified by searching MEDLINE and EMBASE (from 1986 to 2005) and meta-analysis conducted according to meta-analysis of Observational Studies in Epidemiology (MOOSE) group recommendations. Data were reported as pooled relative risk (RR) and 95% confidence intervals (CI) using random-effects models to assess the association of stroke outcomes with PA level. Heterogeneity was investigated, and sensitivity analysis was performed. Stratified analysis by gender was performed. RESULTS Of 992 articles, 13 satisfied all eligibility criteria and were studied. Compared with low PA, moderate PA caused an 11% reduction in risk of stroke outcome (RR = 0.89, 95% CI 0.86-0.93, p < 0.01) and high PA a 19% reduction (RR = 0.81, CI 0.77-0.84, p < 0.01). Among the men, results showed a 12% reduction in risk associated with moderate PA (RR = 0.88, CI 0.82-0.94, p < 0.01) and 19% reduction for high PA (RR = 0.81, CI 0.75-0.87, p < 0.01). Among the women, results showed a 24% reduction in risk for high PA (RR = 0.76, CI 0.64-.89, p < 0.01). There was, however, no significant risk reduction associated with a moderate PA level in women. CONCLUSIONS Increased PA level appears beneficial in reduction of risk of stroke and related outcomes. However, higher levels of PA may be required in women to achieve as significant a risk reduction as in men. An exercise regimen tailored to women to improve related physiological mechanisms will likely be beneficial.

Ethnic and Geographic Variation in Stroke Mortality Trends

Background and Purpose— Magnitude, geographic, and ethnic variation in trends in stroke within the United States require updating for health services and health disparities research. Methods— Data for stroke were analyzed from the US mortality files for 1999 to 2007. Age-adjusted death rates were computed for non-Hispanic African Americans and European Americans aged ≥45 years. Results— Between 1999 and 2007, the age-adjusted death rate per 100 000 for stroke declined both in African Americans and in European Americans of both genders. Among African American females, European American females, and European American males, rates declined by at least 2% annually in every division. Among African American males, rates declined little in the East and West South Central divisions where disparities in trends by urbanization level were found. Conclusions— Between 1999 and 2007, the rate of decline in stroke mortality varied by geographic region and ethnic group.

The impact of body mass index on pulse pressure in obesity.

Objective Pulse pressure, a marker of arterial vascular properties, has been linked to cardiovascular diseases and complications. This study examined the impact of excess body mass and cardiovascular disease risk factors on pulse pressure (PP). Design Cross-sectional and prospective study. Methods Baseline data consist of 219 obese African Americans, with mean ± SD age of 46.8 ± 10.9 years enrolled in a diet and exercise program of weight reduction. A non-invasive monitoring device was used to acquire 24 hourly ambulatory blood pressures. Pulse pressure was calculated as the difference between the average 24-h systolic and diastolic blood pressure and studied as a continuous variable and according to quartiles. The cross-sectional association of pulse pressure with body mass index (BMI) was examined using multivariate linear regression and proportional odds models that controlled for cardiovascular disease risk factors. In addition, we examined prospectively, in 36 participants, the effect of weight loss on pulse pressure, using the Wilcoxon signed ranked test. Results At baseline, a 5 kg/m2 increase in BMI was independently associated with a 35% risk [relative risk (RR) = 1.35, confidence interval (CI) = 1.10–1.65, P < 0.01] in the general study population and 19% (RR = 1.19, CI = 1.07–1.56, P = 0.04) in obese normotensives for increasing PP by one quartile after adjustment for other significant variables. After 3 months of diet and exercise intervention, BMI decreased by an average of 10.6% (P < 0.01) and resulted in an 8.8% (P < 0.01) reduction in PP. Conclusions In the context of obesity, increasing BMI is independently associated with decreasing arterial compliance, as reflected in PP. This association highlights the potential value to cardiovascular health of any reduction in body weight in obese individuals.

Culturally Competent Strategies for Recruitment and Retention of African American Populations into Clinical Trials.

To identify successful recruitment strategies, challenges and best practices for researchers to engage African American communities in clinical studies taken into consideration target participants’ culture and context.

The Metabolically Healthy But Obese Phenotype in African Americans

J Clin Hypertens (Greenwich).

Effect of diet and exercise on pulse pressure and cardiac function in morbid obesity : Analysis of 24-hour ambulatory blood pressure

Blood pressure is a major risk factor for cardiovascular events, although the role of pulse pressure, an independent predictor of arterial stiffness, has recently been emphasized. This study examines the baseline relationship between body mass index (BMI) and blood pressure indexes in 215 obese African Americans enrolled in a diet—exercise program. The subject population was 77% female, with a mean ± SD age of 46.7±10.7 years and a mean BMI of 42.5±7.5 kg/m2. In addition, the authors prospectively examined the effect of weight loss on cardiovascular parameters in a subset of 25 participants. The results show a closer significant correlation between pulse pressure and BMI (β=1.97 kgm−1; p=0.001) than between systolic blood pressure and BMI (β=1.58 kgm1; p=0.020). After 3 months of diet and exercise, average reductions were as follows: BMI, 4.2 kg/m2 (p<0.01); systolic blood pressure, 7.2 mm Hg (p<0.01); pulse pressure, 4.8 mm Hg (p<0.01); and cardiac output, 975 mL/min (p<0.01). Compliance index increased by 0.1 mL/mm Hg/m2 (p=0.03). The results highlight the potential value to cardiovascular health of a modest reduction in body weight in obese individuals.

Anti-Plasmodial Activity of Aroylhydrazone and Thiosemicarbazone Iron Chelators: Effect on Erythrocyte Membrane Integrity, Parasite Development and the Intracellular Labile Iron Pool

Iron chelators inhibit the growth of the malaria parasite, Plasmodium falciparum, in culture and in animal and human studies. We previously reported the anti-plasmodial activity of the chelators, 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), 2-hydroxy-1-naphthylaldehyde 4-methyl-3-thiosemicarbazone (N4mT), and 2-hydroxy-1-naphthylaldehyde 4-phenyl-3-thiosemicarbazone (N4pT). In fact, these ligands showed greater growth inhibition of chloroquine-sensitive (3D7) and chloroquine-resistant (7G8) strains of P. falciparum in culture compared to desferrioxamine (DFO). The present study examined the effects of 311, N4mT and N4pT on erythrocyte membrane integrity and asexual parasite development. While the characteristic biconcave disk shape of the erythrocytes was unaffected, the chelators caused very slight hemolysis at IC50 values that inhibited parasite growth. The chelators 311, N4mT and N4pT affected all stages of the intra-erythrocytic development cycle (IDC) of P. falciparum in culture. However, while these ligands primarily affected the ring-stage, DFO inhibited primarily trophozoite and schizont-stages. Ring, trophozoite and schizont-stages of the IDC were inhibited by significantly lower concentrations of 311, N4mT, and N4pT (IC50=4.45±1.70, 10.30±4.40, and 3.64±2.00μM, respectively) than DFO (IC50=23.43±3.40μM). Complexation of 311, N4mT and N4pT with iron reduced their anti-plasmodial activity. Estimation of the intracellular labile iron pool (LIP) in erythrocytes showed that the chelation efficacy of 311, N4mT and N4pT corresponded to their anti-plasmodial activities, suggesting that the LIP may be a potential source of non-heme iron for parasite metabolism within the erythrocyte. This study has implications for malaria chemotherapy that specifically disrupts parasite iron utilization.

Neuroprotection and Neurodegeneration in Alzheimer’s Disease: Role of Cardiovascular Disease Risk Factors, Implications for Dementia Rates, and Prevention with Aerobic Exercise in African Americans

Prevalence of Alzheimers disease (AD) will reach epidemic proportions in the United States and worldwide in the coming decades, and with substantially higher rates in African Americans (AAs) than in Whites. Older age, family history, low levels of education, and ɛ4 allele of the apolipoprotein E (APOE) gene are recognized risk factors for the neurodegeneration in AD and related disorders. In AAs, the contributions of APOE gene to AD risk continue to engender a considerable debate. In addition to the established role of cardiovascular disease (CVD) risk in vascular dementia, it is now believed that CVD risk and its endophenotype may directly comediate AD phenotype. Given the pleiotropic effects of APOE on CVD and AD risks, the higher rates of CVD risks in AAs than in Whites, it is likely that CVD risks contribute to the disproportionately higher rates of AD in AAs. Though the advantageous effects of aerobic exercise on cognition is increasingly recognized, this evidence is hardly definitive, and data on AAs is lacking. In this paper, we will discuss the roles of CVD risk factors in the development of AD and related dementias, the susceptibility of these risk factors to physiologic adaptation, and fitness-related improvements in cognitive function. Its relevance to AD prevention in AAs is emphasized.

Strong association of fascin expression with triple negative breast cancer and basal-like phenotype in African-American women

Background Fascin, an actin bundling protein, plays a critical role in cell motility due to formation of actin rich protrusions called filopodia, important in cell migration, invasion and metastatic spread. Fascin overexpression has been associated with epithelial to mesenchymal transition and correlates with progression and unfavourable prognosis in breast carcinoma. Objective To evaluate fascin expression by immunohistochemistry and correlate the expression pattern with clinicopathological parameters in breast cancer in African-American (AA) women, in whom triple negative breast cancer (TNBC), an aggressive subtype, is more prevalent. Methods Tissue microarrays were constructed from formalin-fixed, paraffin-embedded blocks of tumour tissue from primary breast carcinomas in 202 AA women. Immunohistochemical detection of fascin was correlated with four major subtypes of breast carcinoma (luminal A, luminal B, human epidermal growth factor receptor 2 and triple negative (TN)) and other clinicopathological factors, including age, grade, tumour size, stage, regional lymph node status and survival. Results We observed a significant association between fascin expression and TN subtype, oestrogen receptor (ER) negativity, progesterone receptor (PR) negativity, Elston–Nottingham (EN) grade 3 and decreased overall survival. There was also a significant association between expression of CK 5/6, a marker of basal-like phenotype, and fascin expression. Conclusion These results suggest that fascin is a marker for TN subtype having a basal-like phenotype and decreased overall survival. Fascin may represent a target for therapy in TNBC in AA women.

The Relationship Between Flow-Mediated Dilatation of the Brachial Artery and Intima-Media Thickness of the Carotid Artery to Framingham Risk Scores in Older African Americans

The objective of this study was to investigate the relationship of flow‐mediated dilatation and intima‐media thickness (IMT) with coronary risk in African Americans (AAs). Endothelial dysfunction and IMT of carotid arteries are considered early steps in atherosclerotic disease process and have been used as surrogate markers of subclinical atherosclerosis. Data were collected on 106 AAs with a mean age of 64.0±6.6 years. Carotid artery IMT was measured with B‐mode ultrasonography, as was brachial artery diameter at rest, during reactive hyperemia, and after nitroglycerin. Percent change in flow‐mediated dilatation (%FMD) was defined as 100×(diameter during reactive hyperemia – resting diameter)/resting diameter. Percent change in nitroglycerin‐mediated dilatation (%NMD) was defined as 100×(diameter with nitroglycerin‐resting diameter)/resting diameter. The Framingham 10‐year risk score (FRS) was calculated for each patient using the National Cholesterol Education Program (NCEP) risk score calculator and participants were categorized into 3 groups with FRS as <10%, 10% to 20%, and >20%. Thirty‐eight participants had risk scores <10%, 26 had 10% to 20%, and 42 >20%. There was a significant inverse relation between %FMD and FRS (P<.0001) and between %NMD and FRS (P<.001). IMT was not statistically different among the risk groups. Endothelial dysfunction assessed by FMD significantly correlates inversely with FRS in AAs. FMD, an index of arterial compliance, appears to be a sensitive and reliable index of cardiovascular disease.