Hina Ahmed

Circulating Progenitor Cells Identify Peripheral Arterial Disease in Patients With Coronary Artery Disease

RATIONALE Peripheral arterial disease (PAD) is a clinical manifestation of extracoronary atherosclerosis. Despite sharing the same risk factors, only 20% to 30% of patients with coronary artery disease (CAD) develop PAD. Decline in the number of bone marrow-derived circulating progenitor cells (PCs) is thought to contribute to the pathogenesis of atherosclerosis. Whether specific changes in PCs differentiate patients with both PAD and CAD from those with CAD alone is unknown. OBJECTIVE Determine whether differences exist in PCs counts of CAD patients with and without known PAD. METHODS AND RESULTS 1497 patients (mean age: 65 years; 62% men) with known CAD were identified in the Emory Cardiovascular Biobank. Presence of PAD (n=308) was determined by history, review of medical records, or imaging and was classified as carotid (53%), lower extremity (41%), upper extremity (3%), and aortic disease (33%). Circulating PCs were enumerated by flow cytometry. Patients with CAD and PAD had significantly lower PC counts compared with those with only CAD. In multivariable analysis, a 50% decrease in cluster of differentiation 34 (CD34+) or CD34+/vascular endothelial growth factor receptor-2 (VEGFR2+) counts was associated with a 31% (P=0.032) and 183% (P=0.002) increase in the odds of having PAD, respectively. CD34+ and CD34+/VEGFR2+ counts significantly improved risk prediction metrics for prevalent PAD. Low CD34+/VEGFR2+ counts were associated with a 1.40-fold (95% confidence interval, 1.03-1.91) and a 1.64-fold (95% confidence interval, 1.07-2.50) increases in the risk of mortality and PAD-related events, respectively. CONCLUSIONS PAD is associated with low CD34+ and CD34+/VEGFR2+ PC counts. Whether low PC counts are useful in screening for PAD needs to be investigated.

Association Between Living in Food Deserts and Cardiovascular Risk

Background— Food deserts (FD), neighborhoods defined as low-income areas with low access to healthy food, are a public health concern. We evaluated the impact of living in FD on cardiovascular risk factors and subclinical cardiovascular disease (CVD) with the hypothesis that people living in FD will have an unfavorable CVD risk profile. We further assessed whether the impact of FD on these measures is driven by area income, individual household income, or area access to healthy food. Methods and Results— We studied 1421 subjects residing in the Atlanta metropolitan area who participated in the META-Health study (Morehouse and Emory Team up to Eliminate Health Disparities; n=712) and the Predictive Health study (n=709). Participants’ zip codes were entered into the United States Food Access Research Atlas for FD status. Demographic data, metabolic profiles, hs-CRP (high-sensitivity C-reactive protein) levels, oxidative stress markers (glutathione and cystine), and arterial stiffness were evaluated. Mean age was 49.4 years, 38.5% male and 36.6% black. Compared with those not living in FD, subjects living in FD (n=187, 13.2%) had a higher prevalence of hypertension and smoking, higher body mass index, fasting glucose, and 10-year risk for CVD. They also had higher hs-CRP (P=0.014), higher central augmentation index (P=0.015), and lower glutathione level (P=0.003), indicative of increased oxidative stress. Area income and individual income, rather than food access, were associated with CVD risk measures. In a multivariate analysis that included food access, area income and individual income, both low-income area and low individual household income, were independent predictors of a higher 10-year risk for CVD. Only low individual income was an independent predictor of higher hs-CRP and augmentation index. Conclusions— Although living in FD is associated with a higher burden of cardiovascular risk factors and preclinical indices of CVD, these associations are mainly driven by area income and individual income rather than access to healthy food.

Depression and chest pain in patients with coronary artery disease

BACKGROUND Depression is common in patients with coronary artery disease (CAD) and is associated with more frequent chest pain. It is however unclear whether this is due to differences in underlying CAD severity. We sought to determine [1] whether depressive symptoms are associated with chest pain independently of CAD severity, [2] whether improvement in depressive symptoms over time is associated with improvement in chest pain and [3] whether the impact of revascularization on chest pain differs between patients with and without depression. METHODS AND RESULTS 5158 patients (mean age 63±12years, 65% male, 20% African American) undergoing cardiac catheterization completed the Seattle Angina Questionnaire (SAQ) and Patient Health Questionnaire-8 (PHQ-8) to assess angina severity and screen for depression, respectively, both at baseline and between 6 and 24months of follow-up. We found significant correlations between PHQ-8 scores and angina frequency (SAQ-AF, r=-0.28), physical limitation (SAQ-PL, r=-0.32) and disease perception (SAQ-DS r=-0.37, all P<0.001), which remained significant after adjustment for clinical characteristics, CAD severity, and anti-depressant use. Improvement in depressive symptoms at follow-up was associated with improvement in angina subscales (SAQ-AF β 1.34, P<0.001), SAQ-PL β 1.85, P<0.001), and SAQ-DS (β 2.12, P<0.001), independently of CAD severity or revascularization. Patients with depression who underwent revascularization had less improvement in chest pain frequency than those without depressive symptoms. CONCLUSIONS Depression is associated with angina, independently of CAD severity. Patients with depression may not derive as adequate symptomatic benefit from revascularization as those without. Whether treatment of underlying depression improves chest pain needs to be further studied.

Bioactive Lipids and Circulating Progenitor Cells in Patients with Cardiovascular Disease

Bone marrow‐derived progenitor cells are mobilized into the peripheral blood after acute myocardial injury and in chronic ischemic heart disease. However, the mechanisms responsible for this mobilization are poorly understood. We examined the relationship between plasma levels of bioactive lipids and number of circulating progenitor cells (CPCs) in patients (N = 437) undergoing elective or emergent cardiac catheterization. Plasma levels of sphingosine‐1 phosphate (S1P) and ceramide‐1 phosphate (C1P) were quantified using mass spectrometry. CPCs were assessed using flow cytometry. S1P levels correlated with the numbers of CD34+, CD34+/CD133+, and CD34+/CXCR4+ CPCs even after adjustment for potential confounding factors. However, no significant correlation was observed between C1P levels and CPC count. Plasma levels of S1P correlated with the number of CPCs in patients with coronary artery disease, suggesting an important mechanistic role for S1P in stem cell mobilization. The therapeutic effects of adjunctive S1P therapy to mobilize endogenous stem cells need to be investigated. Stem Cells Translational Medicine 2017;6:731–735

Cardiovascular Disease Biomarkers and suPAR in Predicting Decline in Renal Function: A Prospective Cohort Study

Introduction Soluble urokinase-type plasminogen activator receptor (suPAR) strongly predicts outcomes and incident chronic kidney disease (CKD) in patients with cardiovascular disease (CVD). Whether the association between suPAR and CKD is a reflection of its overall association with chronic inflammation and poor CVD outcomes is unclear. We examined whether CVD biomarkers, including high-sensitivity C-reactive protein (hs-CRP), fibrin-degradation products (FDPs), heat-shock protein 70 (HSP-70), and high-sensitivity troponin I (hs-TnI) were associated with a decline in kidney function in the Emory Cardiovascular Biobank cohort, in which suPAR levels were shown to be predictive of both incident CKD and CVD outcomes. Methods We measured suPAR, hs-CRP, HSP-70, FDP, and hs-TnI plasma levels in 3282 adults (mean age 63 years, 64% male, 75% estimated glomerular filtration rate [eGFR] >60 ml/min per 1.73 m2). Glomerular filtration rate was estimated using Chronic Kidney Disease–Epidemiology Collaboration (eGFR) at enrollment (n = 3282) and follow-up (n = 2672; median 3.5 years). Urine protein by dipstick at baseline was available for 1335 subjects. Results There was a weak correlation among biomarkers (r range: 0.17−0.28). hs-CRP, FDPs, hs-TnI, and suPAR were independently associated with baseline eGFR and proteinuria. The median yearly decline in eGFR was −0.6 ml/min per 1.73 m2. hs-CRP (β: −0.04; P = 0.46), FDPs (β: −0.13; P = 0.08), HSP-70 (β: 0.05; P = 0.84), or hs-TnI (β: −0.01; P = 0.76) were associated with eGFR decline. suPAR remained predictive of eGFR decline even after adjusting for all biomarkers. Discussion hs-CRP, FDP, HSP-70, and hs-TnI were not associated with eGFR decline. The specific association of suPAR with eGFR decline supported its involvement in pathways specific to the pathogenesis of kidney disease.

Effects of a Health‐Partner Intervention on Cardiovascular Risk

Background Lifestyle modifications are first‐line measures for cardiovascular disease prevention. Whether lifestyle intervention also preserves cardiovascular health is less clear. Our study examined the role of a Health Partner–administered lifestyle intervention on metrics of ideal cardiovascular health. Methods and Results A total of 711 university employees (48±11 years; 66% women, 72% Caucasian/22.5% African Americans) enrolled in a program that promoted healthier lifestyles at Emory University (Atlanta, GA). Anthropometric, laboratory, and physical activity measurements were performed at baseline and at 6 months, 1 year, and 2 years of follow‐up. Results were utilized by the Health Partner to generate a personalized plan aimed at meeting ideal health metrics. Compared to baseline, at each of the 6‐month, 1‐year, and 2‐year follow‐up visits, systolic blood pressure was lower by 3.6, 4.6, and 3.3 mm Hg (P<0.001), total cholesterol decreased by 5.3, 6.5, and 6.4 mg/dL (P<0.001), body mass index declined by 0.33, 0.45, and 0.38 kg/m2 (P<0.001), and the percentage of smokers decreased by 1.3%, 3.5%, and 3.5% (P<0.01), respectively. Changes were greater in those with greater abnormalities at baseline. Finally, the American Heart Association “Lifes Simple 7” ideal cardiovascular health score increased by 0.28, 0.40, and 0.33 at 6 month, 1 year, and 2 years, respectively, compared to baseline visit. Conclusions A personalized, goal‐directed Health Partner intervention significantly improved the cardiometabolic risk profile and metrics of cardiovascular health. These effects were evident at 6 months following enrollment and were sustained for 2 years. Whether the Health Partner intervention improves long‐term morbidity and mortality and is cost‐effective needs further investigation.

Degenerative mitral regurgitation predicts worse outcomes in patients undergoing transcatheter aortic valve replacement

To evaluate the role mitral regurgitation (MR) etiology and severity play in outcomes for patients undergoing transcatheter aortic valve replacement (TAVR).

VITAMIN D3 LEVELS MODULATE CXCR4+ CIRCULATING PROGENITOR CELL COUNTS

The role of 1,25-dihydroxy-vitamin D3 (VitD3) in cardiovascular disease remains controversial. Vitamin D receptors on progenitor cells (PCs) promote maturation and vascular repair by inducing SDF1 expression and homing of CXCR4+ angiogenic myeloid cells. Whether VitD3 levels modulate circulating PCs

DEGENERATIVE VERSUS FUNCTIONAL MITRAL REGURGITATION IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT FOR SEVERE AORTIC STENOSIS

Many patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) have mitral regurgitation (MR). It is suggested that MR affects echocardiographic and clinical outcomes. High risk or inoperable patients who underwent balloon or self-expanding TAVR for AS at two

HIGH-SENSITIVITY TROPONIN-I LEVELS PREDICT LONG-TERM MORTALITY INDEPENDENT OF CORONARY ARTERY DISEASE SEVERITY

High-sensitivity Troponin-I (hs-TnI) as a marker of myocardial injury is predictive of adverse outcomes in patients with coronary artery disease (CAD). Whether the relationship between hs-TnI and outcomes is dependent on underlying CAD severity is unknown. 2826 patients without AMI (mean age 62, 64