Yusuf Ahmed

Oxidative stress is associated with impaired arterial elasticity

AIMS Arterial stiffening may lead to hypertension, greater left ventricular after-load and adverse clinical outcomes. The underlying mechanisms influencing arterial elasticity may involve oxidative injury to the vessel wall. We sought to examine the relationship between novel markers of oxidative stress and arterial elastic properties in healthy humans. METHODS AND RESULTS We studied 169 subjects (mean age 42.6 ± 14 years, 51.6% male) free of traditional cardiovascular risk factors. Indices of arterial stiffness and wave reflections measured included carotid-femoral Pulse Wave Velocity (PWV), Augmentation Index (Aix) and Pulse Pressure Amplification (PPA). Non-free radical oxidative stress was assessed as plasma oxidized and reduced amino-thiol levels (cysteine/cystine, glutathione/GSSG) and their ratios (redox potentials), and free radical oxidative stress as derivatives of reactive oxygen metabolites (dROMs). Inflammation was assessed as hsCRP and interleukin-6 levels. The non-free radical marker of oxidative stress, cystine was significantly correlated with all arterial indices; PWV (r=0.38, p<0.001), Aix (r=0.35, p<0.001) and PPA (r=-0.30, p<0.001). Its redox potential, was also associated with PWV (r=0.22, p=0.01), while the free radical marker of oxidative stress dROMS was associated with Aix (r=0.25, p<0.01). After multivariate adjustment for age, gender, arterial pressure, height, weight, heart rate and CRP, of these oxidative stress markers, only cystine remained independently associated with PWV (p=0.03), Aix (p=0.01) and PPA (p=0.05). CONCLUSIONS In healthy subjects without confounding risk factors or significant systemic inflammation, a high cystine level, reflecting extracellular oxidant burden, is associated with increased arterial stiffness and wave reflections. This has implications for understanding the role of oxidant burden in pre-clinical vascular dysfunction.

Racial differences in arterial stiffness and microcirculatory function between Black and White Americans.

Background Compared with whites, black Americans suffer from a disproportionate burden of cardiovascular disease (CVD). We hypothesized that racial differences in the prevalence of CVD could be attributed, in part, to impaired vascular function in blacks after adjustment for differences in risk factor burden. Methods and Results We assessed vascular function in 385 black and 470 white subjects (mean age, 48±11 years; 45% male). Using digital pulse amplitude tonometry (EndoPAT) we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function, and peripheral augmentation index (PAT‐AIx). Central augmentation index (C‐AIx) and pulse‐wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively, using applanation tonometry (Sphygmocor). Compared with whites, blacks had lower RHI (2.1±0.6 versus 2.3±0.6, P<0.001), greater arterial wave reflections assessed as both PAT‐AIx (20.4±21.5 versus 17.0±22.4, P=0.01) and CAIx (20.8±12.3 versus 17.5±13.3, P=0.001), and greater arterial stiffness, measured as PWV (7.4±1.6 versus 7.1±1.6 m/s, P=0.001). After adjustment for traditional CVD risk factors, black race remained a significant predictor of lower RHI and higher PAT‐AIx and CAIx (all P<0.001) in all subjects and of higher PWV in men (P=0.01). Furthermore, these associations persisted in a subgroup analysis of “healthy” individuals free of CVD risk factors. Conclusion Black race is associated with impaired microvascular vasodilatory function, and greater large arterial wave reflections and stiffness. Because impairment in these vascular indices may be associated with worse long‐term outcomes, they may represent underlying mechanisms for the increased CVD risk in blacks.

Association between Depression and Inflammation - Differences by Race and Sex: The META-Health Study

Objective: To test whether the association between depression and inflammation differs by race and sex. Depressive symptoms have been associated with higher levels of C-reactive protein (CRP). However, few studies have examined this association in samples including a significant number of African Americans, or examined whether the association differs by race and sex. Methods: Depressive symptoms and CRP were assessed in 512 African American and white participants, age 30 to 65 years, as part of the community-based Morehouse and Emory Team up to Eliminate Health Disparities (META-Health) Study. Depression was determined by responses to the Beck Depression Inventory II (BDI-II). Multivariable linear regression models were used to adjust for demographic and metabolic risk factors. Results: African American men had higher total BDI-II scores than white men (p =.03), whereas there was no difference in women. There was a significant race-sex-depression interaction in predicting CRP levels (p =.02). White women with mild to severe depressive symptoms had higher levels of CRP compared with those with minimal to no depressive symptoms (p <.05). There were no differences in levels of CRP by severity of depressive symptoms in white men or African Americans of either sex. Higher BDI-II scores were related to higher CRP levels in white women after adjusting for age and level of education (&bgr; = 0.227, p =.006). However, the association was eliminated after further adjustment for metabolic risk factors (&bgr; = 0.077, p =.35). Conclusions: Although depressive symptoms are associated with inflammation, the association varies by race and sex.CVD = cardiovascular disease; BDI-II = Beck Depression Inventory II; CRP = C-reactive protein; BMI = body mass index; HDL-C = high-density lipoprotein cholesterol

The Association between Depression and Leptin is Mediated by Adiposity

Objective Animal models suggest that impaired leptin production, or leptin resistance despite increased leptin levels, may contribute to depression. The link between leptin and depression could be mediated by obesity, which is more common in depression and increases leptin production. Methods We administered the Beck Depression Inventory–II (BDI-II) to 537 participants (mean [standard deviation (SD)] age = 51 [9] years; female, 61%) enrolled in the Morehouse and Emory Team up to Eliminate Health Disparities (META-Health) study. Leptin levels were examined as continuous log-transformed values. Results Participants with moderate to severe depression had higher levels of leptin (median [interquartile range] 37.7 [17.6–64.9] ng/mL) than those with mild depression (22.9 [7.0–57.9] ng/mL) or minimal to no depression (19.8 ng/mL [7.8–39.1], p = .003). Participants with moderate to severe depression had higher body mass index (BMI) than those with mild or minimal depression (mean [SD] = 33 [8] versus 31 [9] versus 29 [7] kg/m2, p = .001). After multivariate adjustment for age, sex, race, smoking status, hypertension, diabetes, blood pressure, lipids, and C-reactive protein, the BDI-II score remained a significant predictor of leptin levels (&bgr; = 0.093, p = .01). Further adjustment for BMI eliminated the association between the BDI-II score and leptin (&bgr; = 0.03, p = .3). Adjusting for waist circumference in place of BMI revealed similar findings. Conclusions The association between depression and leptin seems to be mediated by increased adiposity in depressed individuals. Abbreviations BDI-II = Beck Depression Inventory–II BMI = body mass index HDL-C = high-density lipoprotein cholesterol

A Randomized Controlled Trial to Promote Long-Term Contraceptive Use Among HIV-Serodiscordant and Concordant Positive Couples in Zambia.

BACKGROUND Countries facing high HIV prevalence often also experience high levels of fertility and low contraceptive use, suggesting high levels of unmet need for contraceptive services. In particular, the unique needs of couples with one or both partners HIV positive are largely missing from many current family planning efforts, which focus on the prevention of pregnancies in the absence of reduction of the risk of HIV and other sexually transmitted infections (STIs). METHODS This article presents an examination of contraceptive method uptake among a cohort of HIV serodiscordant and concordant positive study participants in Zambia. RESULTS Baseline contraceptive use was low; however, exposure to a video-based intervention that provided information on contraceptive methods and modeled desirable future planning behaviors dramatically increased the uptake of modern contraceptive methods. CONCLUSIONS Including information on family planning in voluntary counseling and testing (VCT) services in addition to tailoring the delivery of family planning information to meet the needs and concerns of HIV-positive women or those with HIV-positive partners is an essential step in the delivery of services and prevention efforts to reduce the transmission of HIV. Family planning and HIV prevention programs should integrate counseling on dual method use, combining condoms for HIV/STI prevention with a long-acting contraceptive for added protection against unplanned pregnancy.

Differences in Systemic Oxidative Stress Based on Race and the Metabolic Syndrome: The Morehouse and Emory Team up to Eliminate Health Disparities (META-Health) Study

BACKGROUND Classification schema such as metabolic syndrome may underestimate cardiovascular disease (CVD) risk in African Americans, despite a higher burden of CVD in African Americans. Oxidative stress results from an imbalance of prooxidants and antioxidants and leads to endothelial dysfunction that promotes vascular inflammation and atherosclerosis. Aminothiol markers of oxidative stress are associated with CVD risk factors and metabolic syndrome; however, little is known about racial differences in levels of oxidative stress. We sought to investigate whether oxidative stress would be higher in African Americans compared to whites independently of traditional risk factor burden. METHODS We assessed oxidative stress in a biracial, community-based cohort. In 620 subjects (59% female, 52% African American) in the Morehouse and Emory Team up to Eliminate Health Disparities (META-Health) study, we measured plasma levels of glutathione, an intracellular antioxidant, and its redox potential as a ratio of reduced and oxidized glutathione (E(h) glutathione). RESULTS African Americans had lower glutathione levels (P<0.001) compared to whites. There was a trend toward more oxidized E(h) glutathione (P = 0.07) in African Americans; however, this did not reach statistical significance. After adjustment for demographics and CVD risk factors, African-American race remained a significant correlate of lower glutathione levels (P<0.001) and a more oxidized E(h) glutathione (P = 0.04). After further adjustment for high-sensitivity C-reactive protein (hsCRP), glutathione remained significantly lower in African Americans (P = 0.001). African Americans with or without metabolic syndrome had lower glutathione levels compared to whites with or without metabolic syndrome, respectively (both P ≤ 0.001), and African Americans without metabolic syndrome had a more oxidized E(h) glutathione compared to whites without metabolic syndrome (P = 0.003). CONCLUSIONS African Americans have higher levels of oxidative stress than whites, even after adjustment for differences in CVD risk factors and inflammation. Racial differences in oxidative stress may play a key role in understanding observed racial disparities in CVD.

A genetic risk variant for myocardial infarction on chromosome 6p24 is associated with impaired central hemodynamic indexes

BACKGROUND Genome-wide association studies (GWAS) have identified novel variants associated with myocardial infarction (MI) in Caucasians. We hypothesized that those variants whose mechanism of risk is currently unknown, confer risk via pathways mediating arterial wave reflections which is an increasingly recognized risk factor for cardiovascular disease. METHODS Single-nucleotide polymorphisms (SNPs) at eight MI risk loci were genotyped and correlated with noninvasively determined pulse wave analysis (PWA)-derived central hemodynamic indexes (augmentation index (AIx); augmented pressure (AP); time to reflected wave (TrW) and central systolic blood pressure (SBP) and diastolic BP (DBP)) in two independent Caucasian populations including (i) those free of measured cardiovascular risk factors (n = 133) and (ii) a community-based population (n = 270). RESULTS Of the eight SNPs examined in the healthy group, the variants at loci 6p24 (AIx and AP both P < 0.001, TrW P = 0.02) and 21q22 (AIx P = 0.002, TrW P = 0.037) were significantly associated with PWA indexes. In the replication group, only the 6p24 variant correlated with these phenotypes (AIx P = 0.005, AP P = 0.049, TrW P = 0.013). In the pooled population (n = 403), no new associations were identified but the association with 6p24 and AIx remained significant even after Bonferroni correction and adjustment for covariates including age, mean arterial pressure, height, gender, glucose, cholesterol, body mass index (BMI), and smoking (AIx (P = 0.03)). Each copy of the risk allele C increased the AIx by 3.5%. CONCLUSIONS The GWAS discovered MI risk variant at 6p24 in the protein phosphatase 1 regulator gene (PHACTR1) is associated with adverse arterial wave reflection indexes and may mediate MI risk through this pathway.

The influence of informed consent content on study participants contraceptive knowledge and concerns.

Little is known about how the information presented in the informed consent process influences study outcomes among participants. This study examines the influence of informed consent content on reported baseline contraceptive knowledge and concerns among two groups of HIV-serodiscordant and seroconcordant HIV-positive couples enrolled in research projects at an HIV research center in Lusaka, Zambia. We found significant differences in the reporting of contraceptive knowledge and concerns between couples viewing consent materials that included detailed information about contraception and those viewing consent materials that lacked the detailed information. We conclude that the design of informed consent materials should strike a balance between ensuring that participants give truly informed consent and educating participants in ways that do not compromise the assessment of the impact of behavioral interventions.

Effect of meditation on endothelial function in Black Americans with metabolic syndrome: a randomized trial.

Objectives Psychological stress may play a role in metabolic syndrome. A consequence of metabolic syndrome is endothelial dysfunction, which is also influenced by psychological stress. We sought to compare the effect of consciously resting meditation (CRM), a sound based meditation, with a control intervention of health education (HE) on endothelial function in the setting of metabolic syndrome. Methods Sixty-eight black Americans with metabolic syndrome risk factors (age, 30–65 years) were randomized to either CRM (n = 33) or HE (n = 35); interventions were matched for frequency and duration of sessions and lasted 12 months. Endothelial function was assessed by brachial artery flow-mediated dilation at baseline and at 6 and 12 months. Arterial elasticity, metabolic risk factors, and psychosocial and behavioral variables were secondary end points. Results Although flow-mediated dilation improved in the CRM group for 12 months, this increase was not significantly higher than that in the HE group (p = .51 for the interaction between group and time). Non–endothelium-dependent dilation and arterial elasticity did not change in either group. Most metabolic syndrome risk factors showed beneficial trends in the CRM group only. A risk factor score counting the number of metabolic syndrome components decreased in the CRM group only (p = .049 for the interaction between treatment group and time). Conclusions Among black Americans with metabolic syndrome risk factors, CRM, did not improve endothelial function significantly more than a control intervention of HE. CRM resulted in favorable trends in metabolic syndrome risk factors, which were examined as secondary outcomes.