Cecilia Berardi

Contemporary Trends in Heart Failure With Reduced and Preserved Ejection Fraction After Myocardial Infarction: A Community Study

Major changes have recently occurred in the epidemiology of myocardial infarction (MI) that could possibly affect outcomes such as heart failure (HF). Data describing trends in HF after MI are scarce and conflicting and do not distinguish between preserved and reduced ejection fraction (EF). We evaluated temporal trends in HF after MI. All residents of Olmsted County, Minnesota (n = 2,596) who had a first-ever MI diagnosed in 1990-2010 and no prior HF were followed-up through 2012. Framingham Heart Study criteria were used to define HF, which was further classified according to EF. Both early-onset (0-7 days after MI) and late-onset (8 days to 5 years after MI) HF were examined. Changes in patient presentation were noted, including fewer ST-segment-elevation MIs, lower Killip class, and more comorbid conditions. Over the 5-year follow-up period, 715 patients developed HF, 475 of whom developed it during the first week. The age- and sex-adjusted risk declined from 1990-1996 to 2004-2010, with hazard ratios of 0.67 (95% confidence interval (CI): 0.54, 0.85) for early-onset HF and 0.63 (95% CI: 0.45, 0.86) for late-onset HF. Further adjustment for patient and MI characteristics yielded hazard ratios of 0.86 (95% CI: 0.66, 1.11) and 0.63 (95% CI: 0.45, 0.88) for early- and late-onset HF, respectively. Declines in early-onset and late-onset HF were observed for HF with reduced EF (<50%) but not for HF with preserved EF, indicating a change in the case mix of HF after MI that requires new prevention strategies.

Decade-long trends in atrial fibrillation incidence and survival: a community study.

BACKGROUND Contemporary data on temporal trends in incidence and survival after atrial fibrillation are scarce. METHODS Residents of Olmsted County, Minn., with a first-ever atrial fibrillation or atrial flutter event between 2000 and 2010 were identified. Age- and sex-adjusted incidence rates were standardized to the 2010 US population, and the relative risk of atrial fibrillation in 2010 versus 2000 was calculated using Poisson regression. Standardized mortality ratios of observed versus expected survival were calculated, and time trends in survival were examined using Cox regression. RESULTS We identified 3344 patients with incident atrial fibrillation/atrial flutter events (52% were male, mean age 72.6 years, 95.7% were white). Incidence did not change over time (age- and sex-adjusted rate ratio, 1.01; 95% confidence interval [CI], 0.91-1.13 for 2010 vs 2000). Within the first 90 days, the risk of all-cause mortality was greatly elevated compared with individuals of a similar age and sex distribution in the general population (standardized mortality ratios 19.4 [95% CI, 17.3-21.7] and 4.2 [95% CI, 3.5-5.0] for the first 30 days and 31 to 90 days after diagnosis, respectively). Survival within the first 90 days did not improve over the study period (adjusted hazard ratio, 0.96; 95% CI, 0.71-1.32 for 2010 vs 2000); likewise, no difference in mortality between 2010 and 2000 was observed among 90-day survivors (hazard ratio, 1.05; 95% CI, 0.85-1.31). CONCLUSIONS In the community, atrial fibrillation incidence and survival have remained constant over the last decade. A dramatic and persistent excess risk of death was observed in the 90 days after atrial fibrillation diagnosis, underscoring the importance of early risk stratification.

Self-Rated Health Predicts Healthcare Utilization in Heart Failure

Background Heart failure (HF) patients experience impaired functional status, diminished quality of life, high utilization of healthcare resources, and poor survival. Yet, the identification of patient‐centered factors that influence prognosis is lacking. Methods and Results We determined the association of 2 measures of self‐rated health with healthcare utilization and skilled nursing facility (SNF) admission in a community cohort of 417 HF patients prospectively enrolled between October 2007 and December 2010 from Olmsted County, MN. Patients completed a 12‐item Short Form Health Survey (SF‐12). Low self‐reported physical functioning was defined as a score ≤25 on the SF‐12 physical component. The first question of the SF‐12 was used as a measure of self‐rated general health. After 2 years, 1033 hospitalizations, 1407 emergency department (ED) visits, and 19,780 outpatient office visits were observed; 87 patients were admitted to a SNF. After adjustment for confounding factors, an increased risk of hospitalizations (1.52 [1.17 to 1.99]) and ED visits (1.48 [1.04 to 2.11]) was observed for those with low versus moderate‐high self‐reported physical functioning. Patients with poor and fair self‐rated general health also experienced an increased risk of hospitalizations (poor: 1.73 [1.29 to 2.32]; fair: 1.46 [1.14 to 1.87]) and ED visits (poor: 1.73 [1.16 to 2.56]; fair: 1.48 [1.13 to 1.93]) compared with good‐excellent self‐rated general health. No association between self‐reported physical functioning or self‐rated general health with outpatient visits and SNF admission was observed. Conclusion In community HF patients, self‐reported measures of physical functioning predict hospitalizations and ED visits, indicating that these patient‐reported measures may be useful in risk stratification and management in HF.

Decade-long trends in atrial fibrillation incidence and survival

BACKGROUND Contemporary data on temporal trends in incidence and survival after atrial fibrillation are scarce. METHODS Residents of Olmsted County, Minn., with a first-ever atrial fibrillation or atrial flutter event between 2000 and 2010 were identified. Age- and sex-adjusted incidence rates were standardized to the 2010 US population, and the relative risk of atrial fibrillation in 2010 versus 2000 was calculated using Poisson regression. Standardized mortality ratios of observed versus expected survival were calculated, and time trends in survival were examined using Cox regression. RESULTS We identified 3344 patients with incident atrial fibrillation/atrial flutter events (52% were male, mean age 72.6 years, 95.7% were white). Incidence did not change over time (age- and sex-adjusted rate ratio, 1.01; 95% confidence interval [CI], 0.91-1.13 for 2010 vs 2000). Within the first 90 days, the risk of all-cause mortality was greatly elevated compared with individuals of a similar age and sex distribution in the general population (standardized mortality ratios 19.4 [95% CI, 17.3-21.7] and 4.2 [95% CI, 3.5-5.0] for the first 30 days and 31 to 90 days after diagnosis, respectively). Survival within the first 90 days did not improve over the study period (adjusted hazard ratio, 0.96; 95% CI, 0.71-1.32 for 2010 vs 2000); likewise, no difference in mortality between 2010 and 2000 was observed among 90-day survivors (hazard ratio, 1.05; 95% CI, 0.85-1.31). CONCLUSIONS In the community, atrial fibrillation incidence and survival have remained constant over the last decade. A dramatic and persistent excess risk of death was observed in the 90 days after atrial fibrillation diagnosis, underscoring the importance of early risk stratification.

Mortality Associated With Heart Failure After Myocardial Infarction A Contemporary Community Perspective

Background—Contemporary data are lacking on the prognostic importance of heart failure (HF) after myocardial infarction (MI). We evaluated the prognostic impact of HF post MI according to preserved/reduced ejection fraction and the timing of its occurrence. Methods and Results—All Olmsted County, Minnesota, residents (n=2596) with incident MI diagnosed in 1990 to 2010 and no prior HF were followed through March 2013. Cox models were used to examine (1) the hazard ratios for death associated with HF type and timing and (2) secular trends in survival by HF status. During a mean follow-up of 7.6 years, there were 1116 deaths, 634 in the 902 patients who developed HF (70%) and 482 in the 1694 patients who did not develop HF (28%). After adjustment for age and sex, HF as a time-dependent variable was strongly associated with mortality (hazard ratio =3.31, 95% confidence interval: 2.93–3.75), particularly from cardiovascular causes (hazard ratio =4.20, 95% confidence interval: 3.50–5.03). Further adjustment for MI severity and comorbidity, acute treatment, and recurrent MI moderately attenuated these associations (hazard ratio =2.49 and 2.94 for all-cause and cardiovascular mortality, respectively). Mortality did not differ by ejection fraction, but was higher for delayed- versus early-onset HF (P for heterogeneity =0.002). The age- and sex-adjusted 5-year survival estimates in 2001 to 2010 versus 1990 to 2000 were 82% and 81% among HF-free and 61% and 54% among HF patients, respectively (P for heterogeneity of trends =0.05). Conclusions—HF markedly increases the risk of death after MI. This excess risk is similar regardless of ejection fraction but greater for delayed- versus early-onset HF. Mortality after MI declined over time, primarily as a result of improved HF survival.

P-selectin and subclinical and clinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)

OBJECTIVE P-selectin is a cellular adhesion molecule that has been shown to be crucial in development of coronary heart disease (CHD). We sought to determine the role of P-selectin on the risk of atherosclerosis in a large multi-ethnic population. METHODS Data from the Multi-Ethnic Study of Atherosclerosis (MESA), including 1628 African, 702 Chinese, 2393 non-Hispanic white, and 1302 Hispanic Americans, were used to investigate the association of plasma P-selectin with CHD risk factors, coronary artery calcium (CAC), intima-media thickness, and CHD. Regression models were used to investigate the association between P-selectin and risk factors, Tobit model for CAC, and Cox regression for CHD events. RESULTS Mean levels of P-selectin differed by ethnicity and were higher in men (P<0.001). For all ethnic groups, P-selectin was positively associated with measures of adiposity, blood pressure, current smoking, LDL, and triglycerides and inversely with HDL. A significant ethnic interaction was observed for the association of P-selectin and prevalent diabetes; however, P-selectin was positively associated with HbA1c in all groups. Higher P-selectin levels were associated with greater prevalence of CAC. Over 10.1 years of follow-up, there were 335 incident CHD events. There was a positive linear association between P-selectin levels and rate of incident CHD after adjustment for traditional risk factors. However, association was only significant in non-Hispanic white Americans (HR: 1.81, 95% CI 1.07 to 3.07, P=0.027). CONCLUSION We observed ethnic heterogeneity in the association of P-selectin and risk of CHD.

Circulating cellular adhesion molecules and risk of diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA)

To test the hypothesis that soluble cellular adhesion molecules would be positively and independently associated with risk of diabetes.

Soluble P-selectin predicts lower extremity peripheral artery disease incidence and change in the ankle brachial index: The Multi-Ethnic Study of Atherosclerosis (MESA)

OBJECTIVE To determine the association of circulating P-selectin with prevalent and incident peripheral artery disease (PAD), the ankle brachial index (ABI), and change in the ABI. METHODS The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective population-based cohort study including 6814 European descent, African American, Hispanic and Chinese men and women aged 45-84 at baseline. Four clinical exams took place after the baseline exam. After excluding those with ABI>1.4, prevalent and incident PAD were defined as an ABI≤0.90. ABI progression was defined as progression from a normal ABI (0.91-1.4) to abnormal (≤0.90 or >1.4) at a later exam. RESULTS In adjusted models, each SD (13 ng/mL) higher P-selectin was significantly associated with 0.007 lower ABI (95% CI ((-0.011, -0.004)), p < 0.001), and an average change in the ABI of -0.006 ((-0.010, -0.003, p < 0.001). P-selectin was significantly associated with a 1.17-fold greater odds of prevalent PAD ((1.02, 1.33), p = 0.03), and a 30% greater risk of incident PAD ((1.11, 1.53), p = 0.001), as well as progression from a normal ABI to an ABI≤ 0.90 (p = 0.003), but not to an ABI>1.4 (p = 0.96). Addition of P-selectin to models containing traditional PAD risk factors and markers of inflammation/coagulation significantly improved the net reclassification for ABI progression (p = 0.03), but was only marginally significant for incident PAD (p = 0.06). CONCLUSIONS P-selectin is significantly associated with the development of PAD. However, further research is needed in population-based studies to confirm prospective associations of P-selectin with incident PAD and change in the ABI, as well as its potential predictive ability.

Plasma and serum L-selectin and clinical and subclinical cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA)

L-selectin has been suggested to play a role in atherosclerosis. Previous studies on cardiovascular disease (CVD) and serum or plasma L-selectin are inconsistent. The association of serum L-selectin (sL-selectin) with carotid intima-media thickness, coronary artery calcium, ankle-brachial index (subclinical CVD), and incident CVD was assessed in 2403 participants in the Multiethnic Study of Atherosclerosis. Regression analysis and the Tobit model were used to study subclinical disease; Cox proportional hazards regression, for incident CVD. Mean age was 63 ± 10 years and 47% were male. Mean sL-selectin was significantly different across ethnicities. Within each race/ethnicity, sL-selectin was associated with age and sex; among non-Hispanic whites and African Americans, it was associated with smoking status and current alcohol use. sL-selectin levels did not predict subclinical or clinical CVD after correction for multiple comparisons. Conditional logistic regression models were used to study the association of plasma L-selectin and CVD in 154 incident CVD cases, and 306 age-, sex-, and ethnicity-matched control subjects. The median follow-up time was 8.5 years. L-selectin levels in plasma were significantly lower than in serum and the overall concordance was low. Plasma levels were not associated with CVD. In conclusion, in this large, multiethnic population, soluble L-selectin levels did not predict clinical or subclinical CVD.

Trans-ethnic meta-analysis identifies common and rare variants associated with hepatocyte growth factor levels in the Multi-Ethnic Study of Atherosclerosis (MESA).

Hepatocyte growth factor (HGF) is a mesenchyme‐derived pleiotropic factor that regulates cell growth, motility, mitogenesis, and morphogenesis in a variety of cells, and increased serum levels of HGF have been linked to a number of clinical and subclinical cardiovascular disease phenotypes. However, little is currently known regarding which genetic factors influence HGF levels, despite evidence of substantial genetic contributions to HGF variation. Based upon ethnicity‐stratified single‐variant association analysis and trans‐ethnic meta‐analysis of 6201 participants of the Multi‐Ethnic Study of Atherosclerosis (MESA), we discovered five statistically significant common and low‐frequency variants: HGF missense polymorphism rs5745687 (p.E299K) as well as four variants (rs16844364, rs4690098, rs114303452, rs3748034) within or in proximity to HGFAC. We also identified two significant ethnicity‐specific gene‐level associations (A1BG in African Americans; FASN in Chinese Americans) based upon low‐frequency/rare variants, while meta‐analysis of gene‐level results identified a significant association for HGFAC. However, identified single‐variant associations explained modest proportions of the total trait variation and were not significantly associated with coronary artery calcium or coronary heart disease. Our findings indicate that genetic factors influencing circulating HGF levels may be complex and ethnically diverse.