Socioeconomic Status and Cardiovascular Outcomes: Challenges and Interventions.

Socioeconomic status (SES) has a measurable and significant effect on cardiovascular health. Biological, behavioral, and psychosocial risk factors prevalent in disadvantaged individuals accentuate the link between SES and cardiovascular disease (CVD). Four measures have been consistently associated with CVD in high-income countries: income level, educational attainment, employment status, and neighborhood socioeconomic factors. In addition, disparities based on sex have been shown in several studies. Interventions targeting patients with low SES have predominantly focused on modification of traditional CVD risk factors. Promising approaches are emerging that can be implemented on an individual, community, or population basis to reduce disparities in outcomes. Structured physical activity has demonstrated effectiveness in low-SES populations, and geomapping may be used to identify targets for large-scale programs. Task shifting, the redistribution of healthcare management from physician to nonphysician providers in an effort to improve access to health care, may have a role in select areas. Integration of SES into the traditional CVD risk prediction models may allow improved management of individuals with high risk, but cultural and regional differences in SES make generalized implementation challenging. Future research is required to better understand the underlying mechanisms of CVD risk that affect individuals of low SES and to determine effective interventions for patients with high risk. We review the current state of knowledge on the impact of SES on the incidence, treatment, and outcomes of CVD in high-income societies and suggest future research directions aimed at the elimination of these adverse factors, and the integration of measures of SES into the customization of cardiovascular treatment.

Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes.

RATIONALE: Leukocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow-derived circulating progenitor cells are involved in tissue repair and regeneration. OBJECTIVE: Main objective of this study was to examine the relationship between LTL and progenitor cells and their impact on adverse cardiovascular outcomes. METHODS AND RESULTS: We measured LTL by quantitative polymerase chain reaction in 566 outpatients (age: 63±9 years; 76% men) with coronary artery disease. Circulating progenitor cells were enumerated by flow cytometry. After adjustment for age, sex, race, body mass index, smoking status, and previous myocardial infarction, a shorter LTL was associated with a lower CD34+ cell count: for each 10% shorter LTL, CD34+ levels were 5.2% lower (P<0.001). After adjustment for the aforementioned factors, both short LTL (

Outcome of Subcutaneous Implantable Cardioverter Defibrillator Implantation in Patients with End-Stage Renal Disease on Dialysis.

BACKGROUND: Although the subcutaneous ICD (S-ICD®) is an attractive alternative in patients with end-stage renal disease (ESRD), data on S-ICD outcomes in dialysis patients are lacking. METHODS: Patients with cardiomyopathy undergoing S-ICD implantation in our center were stratified by need for chronic dialysis at the time of implant. The primary endpoint was incidence of death, heart failure hospitalization or appropriate S-ICD shocks, and secondary endpoints were incidence of inappropriate shocks or implant related complications requiring surgical re-intervention. Mean follow-up was longer in the nondialysis cohort (514 ± 495 vs. 227 ± 233 days, P = 0.006), so all endpoints were analyzed using time-dependent comparisons and reported as annual event rates. RESULTS: Out of 79 S-ICD implants included in this analysis, 27 patients were on dialysis. Dialysis patients were older and more likely to be diabetic. Mean ejection fraction across the entire cohort was 26.9% without significant difference between dialysis and nondialysis groups. Although not significant, the incidence of the primary endpoint was higher in the dialysis cohort (23.8%/year vs. 10.9%/year, P = 0.317), driven primarily by a higher rate of appropriate shocks. The rate of inappropriate shocks was similar between groups (dialysis 6.0%/year vs. nondialysis 6.8%/year, P = 0.509). No patients in the dialysis cohort had complications requiring surgical re-intervention versus 6 patients in the nondialysis cohort (P = 0.086). CONCLUSIONS: Our data suggest that S-ICD implantation in dialysis patients is not associated with an excess risk of implant related complications or inappropriate shocks.

Predictors of Long-Term Survival Following Transvenous Extraction of Defibrillator Leads.

BACKGROUND: Little data exist on long-term outcomes following extraction of implantable cardioverter defibrillator (ICD) leads, particularly for noninfectious indications. We sought to identify predictors of long-term survival after ICD lead extraction. METHODS: We retrospectively reviewed ICD lead extractions at our institution (n = 508). Procedural outcomes and long-term survival were ascertained by medical records review. RESULTS: Indication for lead extraction was infection in 32.5% and lead failure in 61.8%. Mean dwell time of the oldest extracted lead was 5.1 ± 5.9 years. Complete procedural success was achieved in 96.5% of cases. Major procedure-related complications occurred in 1.6% with six periprocedural deaths. During a mean follow-up of 866 ± 798 days, survival was significantly worse among patients with infection as the indication for extraction. At 1 year after extraction, survival among those with infection was 88.2%, compared to 95.0% in the lead failure cohort (P < 0.001). Procedural failure was a significant predictor of long-term mortality, even after excluding periprocedural deaths. In multivariate models, the presence of chronic kidney disease, increased number of leads requiring extraction, lower ejection fraction, and procedural failure were predictors of mortality. CONCLUSION: Despite high rates of procedural success, infectious indication for ICD lead extraction is associated with increased long-term mortality. In contrast, among patients undergoing extraction for lead failure, long-term survival was excellent. The presence of procedural failure was a significant predictor of long-term mortality. Further studies will be necessary to better understand the mechanisms by which procedural failure may adversely impact long-term outcomes.

Long-term survival for patients with metabolic syndrome after bioprosthetic or mechanical valve replacement.

BACKGROUND: Metabolic diseases are thought to negatively impact the long-term survival of cardiac patients and have been shown to be associated with reduced durability of bioprosthetic heart valves. The purpose of this study is to determine whether long-term survival of post-valve replacement patients is affected by the presence of metabolic disease, and whether choice of tissue versus mechanical prosthesis impacts survival. METHODS: A retrospective review was conducted of all isolated valve replacements performed between 2002 and 2011 from the STS adult cardiac database of Emory Healthcare Hospitals. A total of 1,222 cases were reviewed, of which 909 patients had AVR (661 tissue, 248 mechanical), and 313 MVR (190 tissue, 123 mechanical). Cardiometabolic syndrome (CMS), in accordance with the World Health Organization (WHO) definition, was present in 242 of 1,222 (19.8%) cases in entire cohort, 203 of 909 (22.3%) in AVR, and 39 of 313 (12.5%) in MVR. Cox proportional hazard regression analysis was used to calculate long-term survival after adjusting for propensity score (PS), Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM), and direct covariates for valve and implant type and stratifying by CMS. RESULTS: In PS adjusted AVR, patients with CMS risk factors had worse survival compared to metabolic risk-free patients (AHR = 3.47), as was the case for MVR (AHR = 4.06). Tissue MVR patients with CMS had higher hazard of death compared to patients with no diabetes and no metabolic risk factors after adjusting for PROM (AHR = 3.33) and direct covariates (AHR = 3.91). CONCLUSIONS: Metabolic diseases negatively impact long-term survival of aortic and mitral valve replacement (MVR) patients. Tissue prostheses are associated with worse long-term survival following MVR.

Ten things to know about ten cardiovascular disease risk factors.

Given rapid advancements in medical science, it is often challenging for the busy clinician to remain up-to-date on the fundamental and multifaceted aspects of preventive cardiology and maintain awareness of the latest guidelines applicable to cardiovascular disease (CVD) risk factors. The "American Society for Preventive Cardiology (ASPC) Top Ten CVD Risk Factors 2021 Update" is a summary document (updated yearly) regarding CVD risk factors. This "ASPC Top Ten CVD Risk Factors 2021 Update" summary document reflects the perspective of the section authors regarding ten things to know about ten sentinel CVD risk factors. It also includes quick access to sentinel references (applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful nutrition, physical inactivity, dyslipidemia, hyperglycemia, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis/smoking, kidney dysfunction and genetics/familial hypercholesterolemia. For the individual patient, other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the "ASPC Top Ten CVD Risk Factors 2021 Update" to provide a succinct overview of things to know about ten common CVD risk factors applicable to preventive cardiology.

Clinical significance of zero coronary artery calcium in individuals with LDL cholesterol ≥190 mg/dL: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Individuals with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are considered high-risk and current guidelines recommend initiating high-intensity statin therapy in this group. We sought to examine the predictive ability of zero CAC in this high-risk group. METHODS: Multi-Ethnic Study of Atherosclerosis participants without clinical cardiovascular disease and baseline LDL-C ≥190 mg/dL were identified. Cardiovascular risk factors were compared between those with CAC = 0 and CAC >0. Multivariable Poisson regression was used to identify predictors of CAC = 0. Association of CAC = 0 with incident cardiovascular events over a median follow-up of 13.2 years was examined using multivariable-adjusted Cox regression. RESULTS: 246 individuals (mean age = 63 ±â€¯9.4 years; 42% male; 31% white; 37% CAC = 0) with LDL-C ≥190 mg/dL were identified (mean LDL-C = 215 ±â€¯27 mg/dL). Age <65 years (RR = 2.17, 95%CI = 1.49-3.23), female sex (RR = 2.10, 95%CI = 1.42-3.10), and no diabetes (RR = 2.22, 95%CI = 1.18-4.17) were associated with CAC = 0. Individuals with CAC = 0 had a lower risk for future cardiovascular events (incidence rate per 1000 person-years = 4.7; 10-year risk = 3.7%; risk/year = 0.4%) than those with CAC >0 (incidence rate per 1000 person-years = 26.4; 10-year risk = 20%; risk/year = 2.0%), adjusted HR 0.25 (95%CI = 0.10-0.66). CONCLUSIONS: Among persons with LDL-C ≥190 mg/dL, younger age, female sex, and the absence of diabetes were associated with CAC = 0. CAC = 0 was associated with a low risk of cardiovascular events, suggesting the utility of CAC assessment for stratifying risk in this high-risk group.

Relation of Living in a "Food Desert" to Recurrent Hospitalizations in Patients With Heart Failure.

Food deserts (FD), low-income areas with low access to healthful foods, are associated with higher burden of cardiovascular risk factors. Few studies have examined the impact of FD on clinical outcomes in heart failure (HF). FD status was assessed in 457 HF patients (mean age 55.9 ± 12.5 years; 50.3% Black) using the Food Desert Research Atlas. The Andersen-Gill extension of Cox model was used to examine the association of living in a FD with risk of repeat hospitalization (all-cause and HF-specific). Patients living in a FD were younger (p = 0.01), more likely to be Black (p <0.0001), less educated (p = 0.003), and less likely to have commercial insurance (p = 0.003). During a median follow-up of 827 (506, 1,379) days, death occurred in 60 (13.1%) subjects, and hospitalizations occurred in 262 (57.3%) subjects. There was no difference in the risk of death based on FD status. The overall frequency of all-cause (94.1 vs 63.6 per 100 patient-years) and HF-specific (59.6 vs 30.5 per 100 patient-years) hospitalizations was higher in subjects who lived in a FD. After adjustment for covariates, living in a FD was associated with an increased risk of repeat all-cause (hazard ratio 1.39, 95% confidence interval 1.19 to 1.63; p = 0.03) and HF-specific (hazard ratio 1.30, 95% confidence interval 1.02 to 1.65; p = 0.03) hospitalizations. In conclusion, patients living in a FD have a higher risk of repeat all-cause and HF-specific hospitalization.

Low Educational Attainment is a Predictor of Adverse Outcomes in Patients With Coronary Artery Disease.

Background Educational attainment is an indicator of socioeconomic status and is inversely associated with coronary artery disease risk. Whether educational attainment level (EAL) among patients with coronary artery disease influences outcomes remains understudied. Methods and Results Patients undergoing cardiac catheterization had their highest EAL assessed using options of elementary/middle school, high school, college, or graduate education. Primary outcome was all-cause mortality and secondary outcomes were a composite of cardiovascular death/non-fatal myocardial infarction and non-fatal myocardial infarction during follow-up. Cox models adjusted for clinically relevant confounders were used to analyze the association of EAL with outcomes. Among 6318 patients (63.5 years, 63% men, 23% black) enrolled, 16%, 42%, 38%, and 4% had received graduate or higher, college, high school, and elementary/middle school education, respectively. During 4.2 median years of follow-up, there were 1066 all-cause deaths, 812 cardiovascular deaths/non-fatal myocardial infarction, and 276 non-fatal myocardial infarction. Compared with patients with graduate education, those in lower EAL categories (elementary/middle school, high school, or college education) had a higher risk of all-cause mortality (hazard ratios 1.52 [95% CI 1.11-2.09]; 1.43 [95% CI 1.17-1.73]; and 95% CI 1.26 [1.03-1.53], respectively). Similar findings were observed for secondary outcomes. Conclusions Low educational attainment is an independent predictor of adverse outcomes in patients undergoing angiographic coronary artery disease evaluation. The utility of incorporating EAL into risk assessment algorithms and the causal link between low EAL and adverse outcomes in this high-risk patient population need further investigation.

Neighborhood poverty and hemodynamic, neuroendocrine, and immune response to acute stress among patients with coronary artery disease.

Living in neighborhoods characterized by poverty may act as a chronic stressor that results in physiological dysregulation of the sympathetic nervous system. No previous study has assessed neighborhood poverty with hemodynamic, neuroendocrine, and immune reactivity to stress. We used data from 632 patients with coronary artery disease. Patients' residential addresses were geocoded and merged with poverty data from the 2010 American Community Survey at the census-tract level. A z-transformation was calculated to classify census tracts (neighborhoods) as either having 'high' or 'low' poverty. Systolic blood pressure, diastolic blood pressure, heart rate, rate-pressure product, epinephrine, interleukin-6, and high-sensitivity C-reactive protein were measured before and after a public speaking stress task. Multilevel models were used for repeated measures and accounting for individuals nested within census tracts. Adjusted models included demographics, lifestyle and medical risk factors, and medication use. Another set of models included propensity scores weighted by the inverse probability of neighborhood status for sex, age, race, and individual-level income. The mean age was 63 years and 173 were women. After adjusting for potential confounders, participants living in high (vs. low) poverty neighborhoods had similar hemodynamic values at rest and lower values during mental stress for systolic blood pressure (157 mmHg vs. 161 mmHg; p = 0.07), heart rate (75 beats/min vs. 78 beats/min; p = 0.02) and rate-pressure product (11839 mmHg x beat/min vs 12579 mmHg x beat/min; p = 0.01). P-values for neighborhood poverty-by-time interactions were <0.05. Results were similar in the propensity weighted models. There were no significant differences in inflammatory and epinephrine responses to mental stress based on neighborhood poverty status. A blunted hemodynamic response to mental stress was observed among participants living in high poverty neighborhoods. Future studies should explore whether neighborhood poverty and blunted hemodynamic response to stress translate into differences in long-term cardiovascular outcomes.

Living in Food Deserts and Adverse Cardiovascular Outcomes in Patients With Cardiovascular Disease.

Background Food deserts ( FDs ), defined as low-income communities with limited access to healthy food, are a growing public health concern. We evaluated the impact of living in FDs on incident cardiovascular events. Methods and Results We recruited 4944 subjects (age 64±12, 64% male) undergoing cardiac catheterization into the Emory Cardiovascular Biobank. Using the US Department of Agriculture definition of FD , we determined whether their residential addresses had (1) poor access to healthy food, (2) low income, or (3) both (= FD ). Subjects were prospectively followed for a median of 3.2 years for myocardial infarction (MI) and death. Fine and Gray's subdistribution hazard models for MI and Cox proportional hazard models for death/ MI were used to examine the association between area characteristics ( FD , poor access, and low income) and the rates of adverse events after adjusting for traditional risk factors. A total of 981 (20%) lived in FDs and had a higher adjusted risk of MI (subdistribution hazard ratio, 1.44 [95% CI, 1.06-1.95]) than those living in non- FDs . In a multivariate analysis including both food access and area income, only living in a low-income area was associated with a higher adjusted risk of MI (subdistribution hazard ratio, 1.40 [1.06-1.85]) and death/ MI (hazard ratio, 1.18 [1.02-1.35]) while living in a poor-access area was not significantly associated with either (subdistribution hazard ratio, 1.05 [0.80-1.38] and hazard ratio, 0.99 [0.87-1.14], respectively). Conclusions Living in an FD is associated with a higher risk of adverse cardiovascular events in those with coronary artery disease. Specifically, low area income of FDs , not poor access to food, was significantly associated with worse outcomes.

Urban-rural differences in mortality for atrial fibrillation hospitalizations in the United States.

BACKGROUND: Cardiovascular outcomes vary between urban and rural hospitals, with worse outcomes in rural settings. OBJECTIVE: The purpose of this study was to examine whether in-hospital mortality for hospitalization for atrial fibrillation (AF) varied between urban and rural hospitals. METHODS: A cross-sectional examination of patients who were hospitalized for AF was performed in the National Inpatient Sample between 2012 and 2014 to compare in-hospital mortality in patients admitted to urban vs rural hospitals. Patients with a principal International Classification of Diseases, Ninth Revision discharge diagnosis of AF were included. Hospitals were classified as urban or rural on the basis of core-based statistical areas. In-hospital mortality was defined as death due to any cause during hospitalization. RESULTS: A total of 248,731 (mean age 69 years; 78% white; 48% women) admissions for AF were identified. Of these, 218,946 (88%) were from urban hospitals and 29,785 (12%) were from rural hospitals. Patients admitted to rural hospitals had a 17% increased risk of death as compared with those admitted to urban hospitals in a multivariable model, which accounted for differences in patient characteristics and potential confounders (odds ratio 1.17; 95% confidence interval 1.04-1.32). Similar results were obtained in a propensity score-matched analysis and in subgroup analyses by sex, race, and region. CONCLUSION: In-hospital mortality of AF is higher in rural hospitals than in urban hospitals. Further research is needed to understand this finding and to develop targeted strategies to reduce mortality in patients admitted for AF in rural hospitals.

Diastolic Blood Pressure and Adverse Outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) Trial.

BACKGROUND: Although diastolic blood pressure (DBP) is independently associated with an increased risk of adverse cardiovascular outcomes in the general population, it is unclear if a similar relationship exists in patients with heart failure with preserved ejection fraction. METHODS AND RESULTS: This analysis included 1703 (mean age, 72±10 years; 50% men; 78% white) patients with heart failure with preserved ejection fraction enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) Trial from the Americas who were treated for hypertension. Multivariable Cox regression was used to examine the risk of hospitalization for heart failure, death, and cardiovascular death associated with DBP. The relationship between hospitalization for heart failure and DBP was linear, with an increased risk observed with decreasing DBP values (≥90 mm Hg: referent; 80-89 mm Hg: hazard ratio [HR], 1.44; 95% confidence interval [CI], 0.85-2.44; 70-79 mm Hg: HR, 1.18; 95% CI, 0.69-2.01; 60-69 mm Hg: HR, 1.54; 95% CI, 0.90-2.63; <60 mm Hg: HR, 2.12; 95% CI, 1.20-3.74; P=0.0055 for trend). The associations of DBP with death (≥90 mm Hg: HR, 1.86; 95% CI, 1.12-3.06; 80-89 mm Hg: HR, 1.23; 95% CI, 0.89-1.70; 70-79 mm Hg: referent; 60-69 mm Hg: HR, 1.20; 95% CI, 0.90-1.59; <60 mm Hg: HR, 1.68; 95% CI, 1.21-2.33) and cardiovascular death (≥90 mm Hg: HR, 2.02; 95% CI, 1.10-3.71; 80-89 mm Hg: HR, 1.17; 95% CI, 0.77-1.79; 70-79 mm Hg: referent; 60-69 mm Hg: HR, 1.16; 95% CI, 0.80-1.70; <60 mm Hg: HR, 1.85; 95% CI, 1.21-2.82) were nonlinear, with a greater risk of each outcome observed with DBP values ≥90 and <60 mm Hg. CONCLUSIONS: DBP values ≥90 and <60 mm Hg are associated with a significant risk of adverse outcomes in patients with heart failure with preserved ejection fraction who are treated for hypertension. Further research is needed to determine optimal DBP targets to reduce the risk of adverse events in patients with heart failure with preserved ejection fraction.

High neighborhood incarceration rate is associated with cardiometabolic disease in nonincarcerated black individuals.

PURPOSE: To examine the association between residence in neighborhoods with high rates of incarceration and cardiometabolic disease among nonincarcerated individuals. METHODS: We used data from two community cohort studies (n = 1368) in Atlanta, Georgia-META-Health and Predictive Health (2005-2012)-to assess the association between neighborhood incarceration rate and cardiometabolic disease, adjusting for individual-level and neighborhood-level factors. We also examined the interaction between race and neighborhood incarceration rate. RESULTS: Individuals living in neighborhoods with high incarceration rates were more likely to have dyslipidemia (odds ratio [OR] = 1.47; 95% confidence interval [CI] = 1.03-2.09) and metabolic syndrome (OR = 1.67; 95% CI = 1.07-2.59) in fully adjusted models. Interactions between race and neighborhood incarceration rate were significant; black individuals living in neighborhoods with high incarceration rates were more likely to have hypertension (OR = 1.59; 95% CI = 1.01-2.49), dyslipidemia (OR = 1.77; 95% CI = 1.12-2.80), and metabolic syndrome (OR = 1.80; 95% CI = 1.09-2.99). CONCLUSIONS: Black individuals living in neighborhoods with high rates of incarceration have worse cardiometabolic health profiles. Criminal justice reform may help reduce race-specific health disparities in the United States.

The Prognostic Significance of Diabetes and Microvascular Complications in Patients With Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: This study examined the prognostic significance of diabetes and microvascular complications in patients with heart failure with preserved ejection fraction (HFpEF). RESEARCH DESIGN AND METHODS: This analysis included 3,385 patients (mean age 69 ± 9.6 years; 49% male; 89% white) with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT). Diabetes and microvascular complications were ascertained by self-reported history and medical record review. Microvascular complications included neuropathy, nephropathy, and retinopathy. Outcomes included hospitalization, hospitalization for heart failure, death, and cardiovascular death. Cox regression was used to examine the risk of each outcome associated with diabetes and microvascular complications. RESULTS: Of the 1,109 subjects (32%) with diabetes, 352 (32%) had at least one microvascular complication. Patients with diabetes and microvascular complications had an increased risk for hospitalization (no diabetes: referent; diabetes + no microvascular complication: hazard ratio [HR] 1.18, 95% CI 1.01, 1.37; diabetes + microvascular complications: HR 1.54, 95% CI 1.25, 1.89; P-trend <0.001), hospitalization for heart failure (no diabetes: referent; diabetes + no microvascular complication: HR 1.51, 95% CI 1.14, 1.99; diabetes + microvascular complications: HR 1.97, 95% CI 1.38, 2.80; P-trend <0.001), death (no diabetes: referent; diabetes + no microvascular complication: HR 1.35, 95% CI 1.04, 1.75; diabetes + microvascular complications: HR 1.73, 95% CI 1.22, 2.45; P-trend = 0.0017), and cardiovascular death (no diabetes: referent; diabetes + no microvascular complication: HR 1.34, 95% CI 0.96, 1.86; diabetes + microvascular complications: HR 1.70, 95% CI 1.09, 2.65; P-trend = 0.018). When the analysis was limited to participants who reported prior hospitalization for heart failure (n = 2,449), a higher risk of rehospitalization for heart failure was observed across diabetes categories (no diabetes: referent; diabetes + no microvascular complication: HR 1.40, 95% CI 1.01, 1.96; diabetes + microvascular complications: HR 1.78, 95% CI 1.18, 2.70; P-trend = 0.0036). CONCLUSIONS: Diabetes is associated with adverse cardiovascular outcomes in HFpEF, and the inherent risk of adverse outcomes in HFpEF patients with diabetes varies by the presence of microvascular complications.

Myocardial Ischemia and Mobilization of Circulating Progenitor Cells.

BackgroundThe response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise-induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing. Methods and ResultsA total of 356 patients with stable coronary artery disease underwent 99mTc-sestamibi myocardial perfusion imaging during exercise (69%) or pharmacological stress (31%). CD34+ and CD34+/chemokine (C-X-C motif) receptor 4 PCs were enumerated by flow cytometry. Change in PC count was compared between patients with and without myocardial ischemia using linear regression models. Vascular endothelial growth factor and stromal-derived factor-1α were quantified. Mean age was 63±9 years; 76% were men. The incidence of ExMI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with ExMI had a significant decrease in CD34+/chemokine (C-X-C motif) receptor 4 (-18%, P=0.01) after stress that was inversely correlated with the magnitude of ischemia (r=-0.19, P=0.003). In contrast, patients without ExMI had an increase in CD34+/chemokine (C-X-C motif) receptor 4 (14.7%, P=0.02), and those undergoing pharmacological stress had no change. Plasma vascular endothelial growth factor levels increased (15%, P<0.001) in all patients undergoing exercise stress testing regardless of ischemia. However, the change in stromal-derived factor-1α level correlated inversely with the change in PC counts in those with ExMI (P=0.03), suggesting a greater decrease in PCs in those with a greater change in stromal-derived factor-1α level with exercise. ConclusionsExMI is associated with a significant decrease in circulating levels of CD34+/chemokine (C-X-C motif) receptor 4 PCs, likely attributable, at least in part, to stromal-derived factor-1α-mediated homing of PCs to the ischemic myocardium. The physiologic consequences of this uptake of PCs and their therapeutic implications need further investigation.

High-Sensitivity Troponin I Levels and Coronary Artery Disease Severity, Progression, and Long-Term Outcomes.

BACKGROUND: The associations between high-sensitivity troponin I (hsTnI) levels and coronary artery disease (CAD) severity and progression remain unclear. We investigated whether there is an association between hsTnI and angiographic severity and progression of CAD and whether the predictive value of hsTnI level for incident cardiovascular outcomes is independent of CAD severity. METHODS AND RESULTS: In 3087 patients (aged 63±12 years, 64% men) undergoing cardiac catheterization without evidence of acute myocardial infarction, the severity of CAD was calculated by the number of major coronary arteries with ≥50% stenosis and the Gensini score. CAD progression was assessed in a subset of 717 patients who had undergone ≥2 coronary angiograms >3 months before enrollment. Patients were followed up for incident all-cause mortality and incident cardiovascular events. Of the total population, 11% had normal angiograms, 23% had nonobstructive CAD, 20% had 1-vessel CAD, 20% had 2-vessel CAD, and 26% had 3-vessel CAD. After adjusting for age, sex, race, body mass index, smoking, hypertension, diabetes mellitus history, and renal function, hsTnI levels were independently associated with the severity of CAD measured by the Gensini score (log 2 ß=0.31; 95% confidence interval, 0.18-0.44; P<0.001) and with CAD progression (log 2 ß=0.36; 95% confidence interval, 0.14-0.58; P=0.001). hsTnI level was also a significant predictor of incident death, cardiovascular death, myocardial infarction, revascularization, and cardiac hospitalizations, independent of the aforementioned covariates and CAD severity. CONCLUSIONS: Higher hsTnI levels are associated with the underlying burden of coronary atherosclerosis, more rapid progression of CAD, and higher risk of all-cause mortality and incident cardiovascular events. Whether more aggressive treatment aimed at reducing hsTnI levels can modulate disease progression requires further investigation.

Peripheral artery disease and risk of adverse outcomes in heart failure with preserved ejection fraction.

BACKGROUND: Peripheral artery disease (PAD) in heart failure with preserved ejection fraction (HFpEF) is associated with an increased mortality risk, but the risk of individual outcomes associated with PAD in this patient group is less clear. HYPOTHESIS: PAD is associated with adverse outcomes in HFpEF, including hospitalization and specific cardiovascular outcomes. METHODS: We examined the association between PAD and adverse outcomes in 3385 patients with HFpEF (mean age, 69 ± 9.6 years; 49% male; 89% white) from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT). Baseline PAD was identified by self-reported history and medical-record review. The following outcomes were adjudicated by a clinical endpoint committee: hospitalization, hospitalization for heart failure (HF), myocardial infarction, stroke, death, and cardiovascular death. RESULTS: Over a median follow-up of 3.4 years (interquartile range, 2.0-4.9 years), an increased risk for hospitalization (hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.16-1.60), myocardial infarction (HR: 1.69, 95% CI: 1.07-2.67), death (HR: 1.56, 95% CI: 1.22-1.99), and cardiovascular death (HR: 1.53, 95% CI: 1.12-2.10) was observed for those with PAD compared with those without PAD. PAD was not associated with incident stroke. The association between PAD and hospitalization for HF was limited to participants with prior history of HF hospitalization (n = 2449; HR: 1.51, 95% CI: 1.09-2.13). CONCLUSIONS: PAD increases the risk for adverse outcomes in HFpEF and is associated with HF rehospitalization. Practitioners should be aware of the inherent risk associated with PAD in HFpEF.

Heart rate and the risk of adverse outcomes in patients with heart failure with preserved ejection fraction.

Background Although high resting heart rates are associated with adverse outcomes in heart failure with reduced ejection, the reports for heart failure with preserved ejection fraction (HFpEF) are conflicting. Design A secondary analysis was conducted in order to examine the relationship between resting heart rate and adverse outcomes in 2705 patients (mean age = 68 ± 10 years; 47% men; 88% white) with HFpEF who were in sinus rhythm from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). Methods Baseline heart rate was obtained from baseline electrocardiogram data. Outcomes were adjudicated by a clinical end-point committee and included the following factors: hospitalisation, hospitalisation for heart failure, death and cardiovascular death. Results Over a median follow-up of 3.4 years (25th-75th percentiles = 2.0-4.9 years), a total of 1157 hospitalisations, 311 hospitalizations for heart failure, 369 deaths and 233 cardiovascular deaths occurred. An increased risk (per 5-beats per minute [bpm] increase) for hospitalisation (hazard ratio [HR] = 1.03, 95% confidence interval [CI] = 1.004-1.060), hospitalisation for heart failure (HR = 1.10, 95% CI = 1.05-1.15), death (HR = 1.10, 95% CI = 1.06-1.16) and cardiovascular death (HR = 1.13, 95% CI = 1.07-1.19) was observed. When the analysis was limited to those who did not report the use of ß-blockers, the magnitude of the association for each outcome (per 5-bpm increase) was not materially altered (hospitalisation: HR = 1.03, 95% CI = 0.97-1.09; hospitalisation for heart failure: HR = 1.12, 95% CI = 0.98-1.27; death: HR = 1.16, 95% CI = 1.05-1.28; cardiovascular death: HR = 1.12, 95% CI = 0.99-1.27). Conclusion High resting heart rate is a risk factor for adverse outcomes in patients with HFpEF, and future studies are needed in order to determine whether reducing heart rate improves outcomes in HFpEF.