Gerber, Yariv

Background: The decline in cardiovascular disease (CVD) mortality in the United States noted since the mid 1970s has recently leveled off. This has generated concern and a need for further analyses to understand geographic variation, cause-specific deaths, location of death, and age-specific trends. Methods: Death certificate data obtained from the Minnesota Department of Health were used for analysis. The American Heart Association (AHA) classification was applied to the underlying cause of death to generate the following CVD categories: coronary heart disease (CHD), non-CHD diseases of the heart, and non-cardiac circulatory diseases. Temporal trends in death rates were explored by negative binomial regression, which enables estimates of age- and sex-adjusted average annual percentage changes (AAPCs). Differences in AAPCs between 2000-2009 and 2010-2017 were tested overall and across demographic, CVD, and location of death categories. Results: CVD mortality rates, which were declining in 2000-2009, have leveled off in 2010-2017 (Table). These trends were observed across all subgroups. After adjusting for sex, the age group that drove the decline in rates from 2000-2009 was the 65-84 year old group, which experienced no change in rates from 2010-2017. Across CVD categories, after adjusting for age and sex, the decline in rates from 2000-2009 was largely attributable to steep reductions in CHD and non-cardiac circulatory diseases, with lesser reduction in non-CHD diseases of the heart. In 2010-2017, CHD and non-cardiac circulatory diseases rates showed no change, whereas the rate of non-CHD diseases of the heart increased. The rates for in- and out-of-hospital deaths improved in 2000-2009 with no further improvement observed in 2010-2017. Conclusions: CVD mortality rates are no longer declining in Minnesota, paralleling national trends. These trends are particularly concerning for non-CHD diseases of the heart.

Background Current American Heart Association/American College of Cardiology guidelines recommend the GRACE (Global Registry of Acute Coronary Events) and TIMI (Thrombolysis in Myocardial Infarction) scores to assess myocardial infarction ( MI ) prognosis. Changes in the epidemiological characteristics of MI and the availability of new biomarkers warrant an assessment of the performance of these scores in contemporary practice. We assessed the following: (1) the performance of GRACE and TIMI to predict 1‐year mortality in a cohort of patients stratified by ST ‐segment elevation MI (STEMI) and non‐STEMI ( NSTEMI ) and (2) the incremental discriminatory power of soluble suppression of tumorigenicity‐2, a myocardial fibrosis biomarker. Methods and Results Olmsted County, Minnesota, residents with incident MI (N=1401) were recruited prospectively from November 1, 2002 to December 31, 2012 (mean age, 67 years; 61% men; 79% with NSTEMI ). Baseline data were used to calculate risk scores; soluble suppression of tumorigenicity‐2 was measured in stored plasma samples obtained at index MI . C ‐statistics adapted to survival data were used to assess the discriminatory power of the risk scores and the improvement gained by adding other markers. During the first year of follow‐up, 190 patients (14%) died. The discriminatory performance to predict death was reasonable for GRACE and poor for TIMI , and was generally worse in those with NSTEMI versus those with STEMI. In people with NSTEMI , sequential addition of comorbidities and soluble suppression of tumorigenicity‐2 substantially improved the c ‐statistic over GRACE (from 0.78 to 0.80 to 0.84) and TIMI (from 0.61 to 0.73 to 0.81), respectively (all P ≤0.05). Conclusions Guideline‐recommended scores for risk assessment after MI underperform in contemporary community patients, particularly those with NSTEMI, which now represents most infarcts. Incorporating comorbidities and soluble suppression of tumorigenicity‐2 substantially improves risk prediction, thereby delineating opportunities to improve clinical care.

Objectives To investigate the effect of the number and type of comorbid conditions on death and hospitalizations in individuals with incident heart failure ( HF ). Design Population‐based cohort study. Setting Olmsted County, Minnesota. Participants Olmsted County, Minnesota, residents with incident HF from 2000 to 2010 (mean age 76 ± 14, 56% female) (N = 1,714). Measurements The prevalence of 16 chronic conditions obtained at HF diagnosis classified into three groups: cardiovascular ( CV ) related, other physical, and mental. Results The mean number of conditions per participant was 2.6 ± 1.5 for CV ‐related conditions, 1.3 ± 1.1 for other physical conditions, and 0.30 ± 0.61 for mental conditions. After a mean follow‐up of 4.2 years, 1,073 deaths and 6,306 hospitalizations had occurred. After adjustment for age, sex, ejection fraction, in‐ or outpatient status, and number of other conditions, an increase of one other physical condition was associated with a 14% ( HR = 1.14, 95% CI = 1.08–1.20) greater risk of death and a 26% ( HR = 1.26, 95% CI = 1.20–1.32) greater risk of hospitalization, and an increase of one mental condition was associated with a 31% ( HR = 1.31, 95% CI = 1.19–1.44) greater risk of death and an 18% ( HR = 1.18, 95% CI = 1.07–1.29) greater risk of hospitalization. In contrast, an increase of one CV ‐related condition was not associated with greater risk of death and was associated with a 10% ( HR = 1.10, 95% CI = 1.06–1.15) greater risk of hospitalization. Conclusion CV ‐related conditions are the most common type of comorbid conditions in individuals with HF , but other physical and mental conditions are more strongly associated with death and hospitalizations. This underscores the effect of non‐ CV conditions on outcomes in HF .

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.

Background: To assess whether the individual housing-based socioeconomic status (SES) measure termed HOUSES was associated with post-myocardial infarction (MI) mortality. Methods: The study was designed as a population-based cohort study, which compared post-MI mortality among Olmsted County, Minnesota, USA, residents with different SES as measured by HOUSES using Cox proportional hazards models. Subjects’ addresses at index date of MI were geocoded to real property data to formulate HOUSES (a z-score for housing value, square footage, and numbers of bedrooms and bathrooms). Educational levels were used as a comparison for the HOUSES index. Results: 637 of the 696 eligible patients with MI (92%) were successfully geocoded to real property data. Post-MI survival rates were 60% (50–72), 78% (71–85), 72% (60–87), and 87% (81–93) at 2 years for patients in the first (the lowest SES), second, third, and fourth quartiles of HOUSES, respectively (p < 0.001). HOUSES was associated with post-MI all-cause mortality, controlling for all variables except age and comorbidity (p = 0.036) but was not significant after adjusting for age and comorbidity (p = 0.24). Conclusions: Although HOUSES is associated with post-MI mortality, the differential mortality rates by HOUSES were primarily accounted for by age and comorbid conditions. HOUSES may be useful for health disparities research concerning cardiovascular outcomes, especially in overcoming the paucity of conventional SES measures in commonly used datasets.

Background— Data on the association between myocardial infarction (MI) and fractures are scarce. Recent changes in the epidemiology of MI justify exploring this relationship. We evaluated whether MI constitutes a risk factor for osteoporotic fracture and examined secular trends in this association. Methods and Results— Consecutive Olmsted County, Minnesota, residents with incident MI diagnosed in 1979 to 2006 and community control subjects individually matched (1:1) to cases on age, sex, and year of onset (n=6642) were followed up through 2009. Outcome measures were time to osteoporotic fracture, overall and by anatomic site, and death. Fracture incidence rates were stable in controls but increased markedly over time among MI cases. Accordingly, although an overall excess of fracture risk after MI was observed (adjusted hazard ratio, 1.32; 95% confidence interval, 1.12 to 1.56), substantial temporal variations were noted (1979 to 1989: hazard ratio, 0.81; 95% confidence interval, 0.58 to 1.12; 1990 to 1999: hazard ratio, 1.47; 95% confidence interval, 1.10 to 1.96; 2000 to 2006: hazard ratio, 1.73; 95% confidence interval, 1.32 to 2.27; P for trend <0.001). Trends were similar regardless of age, sex or fracture site. Conversely, the overall hazard ratio for death in MI cases versus controls did not change materially despite a continuous decline in 30-day case fatality rate (12.5% in 1979 to 1989; 6.7% in 2000 to 2006). Observed changes in the baseline prevalence of cardiovascular risk factors, MI characteristics, and comorbidities did not fully account for the trends in fracture risk. Conclusions— Over the past decades, the association between MI and osteoporotic fractures increased steadily. The trend is consistent with the displacement of post-MI outcomes toward noncardiovascular events, highlighting the need for comprehensive prevention strategies to accommodate the changing epidemiology of MI.

Background— In 2000, the definition of myocardial infarction (MI) changed to rely on troponin rather than creatine kinase (CK) and its MB fraction (CK-MB). The implications of this change on trends in MI incidence and outcome are not defined. Methods and Results— This was a community study of 2816 patients hospitalized with incident MI from 1987 to 2006 in Olmsted County, Minnesota, with prospective measurements of troponin and CK-MB from August 2000 forward. Outcomes were MI incidence, severity, and survival. After troponin was introduced, 278 (25%) of 1127 incident MIs met only troponin-based criteria. When cases meeting only troponin criteria were included, incidence did not change between 1987 and 2006. When restricted to cases defined by CK/CK-MB, the incidence of MI declined by 20%. The incidence of non–ST-segment elevation MI increased markedly by relying on troponin, whereas that of ST-segment elevation MI declined regardless of troponin. The age- and sex-adjusted hazard ratio of death within 30 days for an infarction occurring in 2006 (compared with 1987) was 0.44 (95% confidence interval, 0.30 to 0.64). Among 30-day survivors, survival did not improve, but causes of death shifted from cardiovascular to noncardiovascular ( P =0.001). Trends in long-term survival among 30-day survivors were similar regardless of troponin. Conclusions— Over the last 2 decades, a substantial change in the epidemiology of MI occurred that was only partially mediated by the introduction of troponin. Non–ST-segment elevation MIs now constitute the majority of MIs. Although the 30-day case fatality improved markedly, long-term survival did not change, and the cause of death shifted from cardiovascular to noncardiovascular.

Background— Mortality among patients with heart failure is high. Though individual biomarkers have been investigated to determine their value in mortality risk prediction, the role of a multimarker strategy requires further evaluation. Methods and Results— Olmsted County residents presenting with heart failure from July 2004 to September 2007 were recruited to undergo biomarker measurement. We investigated whether addition of C-reactive protein, B-type natriuretic peptide, and troponin T to a model including established risk indicators improved 1-year mortality risk prediction using the c statistic, integrated discrimination improvement, and net reclassification improvement. Among 593 participants, the mean age was 76.4 years, and 48% were men. After 1 year of follow-up, 122 (20.6%) participants had died. Patients with C-reactive protein (<11.8 mg/L), B-type natriuretic peptide (<350 pg/mL), and troponin T (≤0.01 ng/mL) less than the median had low 1-year mortality (3.3%), whereas those with 2 or 3 biomarkers greater than the median had markedly increased mortality (30.8% and 35.5%, respectively). The addition of 2 or more biomarkers to the model offered greater improvement in 1-year mortality risk prediction than use of a single biomarker. The combination of C-reactive protein and B-type natriuretic peptide resulted in an increase in the c statistic from 0.757 to 0.810 ( P <0.001), an integrated discrimination improvement gain of 7.1% ( P <0.001), and a net reclassification improvement of 22.1% ( P <0.001). Use of all 3 biomarkers offered no incremental gain (integrated discrimination improvement gain 0.7% versus C-reactive protein+B-type natriuretic peptide, P =0.065). Conclusions— Biomarkers improved 1-year mortality risk prediction beyond established indicators. The use of a 2-biomarker combination was superior to a single biomarker in risk prediction, though addition of a third biomarker conferred no added benefit.