Gerber, Yariv

Background: Recent findings suggest a role for heart failure in the etiology of osteoporotic fractures, but the nature of the relationship is unclear and community data are lacking. Methods and Results: We conducted a community-based case-control study comparing prior osteoporotic fractures among Olmsted County, Minnesota, residents newly diagnosed with heart failure in 1979-2002 (cases) to age- and sex-matched community controls without heart failure (961 pairs; mean age: 76 years; 54% women). Subjects were then followed forward in time to July 2009 to evaluate the risk of fracture subsequent to the heart failure diagnosis. Prior fractures were more frequent in heart failure cases than controls: 23% versus 19%, P =0.02; adjusted odds ratio (OR) for any osteoporotic fracture 1.39 (95% CI: 1.07-1.81). This was related to hip fractures (OR: 1.82; 95% CI: 1.25-2.66) with little or no association with other fractures. Over a mean follow-up of 7.5 years, 536 new osteoporotic fractures occurred in 444 individuals. The adjusted fracture risk was higher among heart failure patients compared to controls (hazard ratio [HR]: 1.32; 95% CI: 0.98-1.79), again largely attributable to hip fractures (HR: 1.58; 95% CI: 1.03-2.41). Conclusions: Patients diagnosed with heart failure experience an excess risk of fractures both before and after the diagnosis of heart failure, which is related to hip fractures. These findings suggest common underlying and co-occurring mechanisms for heart failure and hip fracture and underscore the crucial importance of preventing falls in elderly heart failure patients.

Background: Heart failure (HF) patients are experiencing an epidemic of hospitalizations. Nevertheless, data on the frequency and distribution of hospitalizations over the course of the disease are lacking. Methods: We determined the rates of hospitalizations during periods of follow-up in Olmsted County, MN residents with incident HF from 2000-2010. HF was identified using ICD-9 code 428 and validated by the Framingham criteria. All hospitalizations were obtained for the 2 years following incident HF and each was categorized as due to HF, other cardiovascular (ICD-9 codes 390-427, 429-459), or non-cardiovascular causes. Follow-up was divided into discrete time periods (epochs): 0-30, 31-182, 183-365, and 366-730 days. Negative binomial regression examined associations between epochs of follow-up time and hospitalizations. Results: Among 1702 incident HF patients (mean age 76, 44% male), 1143 (67%) were hospitalized at index. Over the 2 year follow-up, 3008 hospitalizations were observed among 1136 patients, and 351 patients were hospitalized within 30 days of incident HF (median time from HF to hospitalization: 11 days). The majority of hospitalizations were due to non-cardiovascular causes (63% vs. 14% HF, 23% other cardiovascular); however, a larger proportion of HF and other cardiovascular hospitalizations were observed within the first 30 days (52% non-cardiovascular, 18% HF, 30% other cardiovascular) compared to the other time periods. The rate of hospitalization was highest within the first 30 days and was similar across sex, presentation of incident HF (inpatient, outpatient), and type of HF (preserved (≥50%), reduced (<50%) ejection fraction) (Table). Conclusions: HF patients experience high rates of hospitalizations, particularly within the first 30 days, and the majority of hospitalizations are for non-cardiovascular causes. Continued efforts to manage comorbid conditions and reduce hospitalizations in HF patients are needed.

Background: There is growing awareness of an association between cardiovascular disease (CVD) and fractures, and a temporal increase in fracture risk after myocardial infarction has been noted but the mechanisms are not delineated. To evaluate this relationship, we systematically examined the association of hip fracture with all disease categories and assessed related secular trends. Methods: Using resources of the Rochester Epidemiology Project, a population-based incident case-control study was conducted. Disease history was compared between all Olmsted County, Minnesota, residents aged 50 years or older with a first hip fracture in 1985–2006 and community control subjects individually matched (1:1) to cases on age, sex, and index year (n=3,808; mean age [SD], 82 [9] years; 76% women). Results: All CVD and numerous non-CVD categories (e.g., infectious diseases, nutritional and metabolic diseases, mental disorders, diseases of the nervous system and sense organs, and diseases of the respiratory system) were associated with fracture risk. However, increasing temporal trends were almost exclusively detected in categories of CVD (Figure). The largest increases in association were observed for ischemic heart disease, other forms of heart disease (including heart failure), hypertension, and diabetes and were more pronounced among elderly women than other demographic groups. Conclusions: While the association with hip fracture was not specific to CVD, temporal increases were mainly detected in cardio-metabolic diseases, all of which have also been linked previously to frailty. This could delineate a common pathway that warrants further investigation.

Objective: To compare two measures of frailty in a community cohort of heart failure (HF) patients. Background: Frailty is increasingly recognized as an important prognostic indicator in HF. Several methods have been proposed to measure frailty. Some conceptualize frailty as a biological phenotype, while others define it as an accumulation of deficits (impairments, disabilities, comorbid diseases), termed the Cumulative Deficit Index (CDI). Each approach has conceptual strengths and limitations; a distinct feature of the CDI is the ability to extract data from medical records. These two methods have never been compared in a community HF cohort. Methods: Olmsted, Dodge and Fillmore County, MN residents with HF between 10/2007 and 12/2010 were prospectively recruited to assess the frailty phenotype. The biological frailty phenotype was defined as ≥3 of the following: unintentional weight loss >10 lbs. in 1 year, physical exhaustion, weak grip strength, and slowness and low activity measured by the SF-12 physical component score. Intermediate frailty was defined as having 1–2 components. The CDI was based on 33 deficits and defined as the proportion of deficits present for each patient. Results: Among 131 patients (mean age 70.5±14, 62% male), according to the biological frailty phenotype definition 18% were frail, 50% intermediate frail and 31% not frail. The CDI ranged from 0.03–0.70, with a mean (SD) of 0.22 (0.12). The CDI was significantly correlated with the frailty phenotype (r=0.59, p<0.001). The mean (SD) of the CDI was 0.35 (0.14), 0.21 (0.10) and 0.15 (0.07) among the frail, intermediate frail and not frail phenotypes (Figure). Conclusion: The CDI is significantly associated with the biological frailty phenotype and can thus be used as an alternative approach to measure frailty in HF. As the components of the biological frailty phenotype are not routinely assessed clinically, the CDI, which can be ascertained from medical records, is a feasible approach to ascertain frailty in large cohorts.

Background: Whether age alone explains the comorbidity burden in heart failure (HF) is unclear. In particular, differences in the burden of co-morbid conditions in HF patients compared to population controls has not been well documented. Methods: The prevalence of 17 chronic conditions defined by the US Department of Health and Human Services were obtained in 1746 incident HF patients from 2000-2010 and controls matched 1:1 on sex and age from Olmsted County, MN. Conditions were ascertained requiring 2 occurrences of a diagnostic code. Logistic regression determined associations of each condition with HF. Results: Among the 1746 matched pairs (mean age 76.2 years, 43.5% men), the prevalence was higher in HF cases for all conditions (p<0.05) except dementia and osteoporosis. After adjusting for all conditions, hypertension, coronary artery disease, arrhythmia, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hepatitis, and substance abuse were significantly more common in HF (figure). More than a 2-fold increased odds of hepatitis, arrhythmia, and coronary artery disease was observed among HF cases. Arrhythmia (34.2%), hypertension (31.1%), and coronary artery disease (27.8%) had the largest attributable risk of HF; for example, assuming a causal relationship, if arrhythmias were eliminated, 34% of HF would be avoided. Conclusions: Compared to age- and sex-matched controls, HF patients have a higher prevalence of many chronic conditions, indicating the excess comorbidity in HF is not due to age alone. Some cardiovascular conditions, including arrhythmia, coronary artery disease, and hypertension were more common in HF. Of the non-cardiovascular conditions, hepatitis had the strongest association with HF and was an unanticipated finding that deserves additional investigation. It is important to understand comorbidities as they play a key role in the excess mortality and healthcare utilization experienced by HF patients.

Background: Little is known about the association between coronary artery disease (CAD) and the risk of heart failure (HF) after myocardial infarction (MI), and whether it differs by reduced (HFrEF) or preserved (HFpEF) ejection fraction (EF) has yet to be determined. Subjects and Methods: Olmsted County, Minnesota residents (n=1,924; mean age, 64 years; 66% male) with first MI diagnosed in 1990-2010 and no prior HF were followed through 2013. Framingham Heart Study criteria were used to define HF, which was further classified according to EF (applying a 50% cutoff). The extent of angiographic CAD was defined at index MI according to the number of major epicardial coronary arteries with ≥50% lumen diameter obstruction. Fine & Gray and Cox proportional hazards regression models were used to assess the association of CAD categories with incidence of HF, and multiple imputation methodology was applied to account for the 19% with missing EF data. Results: During a mean (SD) follow-up of 6.7 (5.9) years, 594 patients developed HF. Adjusted for age and sex, with death considered a competing risk, the cumulative incidence rates of HF among patients with 1- (n=581), 2- (n=622), and 3-vessel disease (n=721) were 11.2%, 14.6% and 20.5% at 30 days; and 18.1%, 22.3% and 29.4% at 5 years after MI, respectively. The increased risk of HF with greater number of occluded vessels was only modestly attenuated after further adjustment for patient and MI characteristics, and did not differ materially by EF (Table). Conclusions: The extent of angiographic CAD expressed by the number of diseased vessels is independently associated with HF incidence after MI. The association is evident promptly after MI and applies to both HFrEF and HFpEF.

Introduction: Mortality among patients with heart failure (HF) is high. Though individual biomarkers have been studied to determine their value in risk prediction, the role of a multimarker strategy in predicting mortality above established risk indicators requires evaluation in a relevant cohort using robust analytical methods. Objective: To determine whether adding C-reactive protein (CRP), B-type natriuretic peptide (BNP), and troponin T (TnT) to established risk indicators improved HF mortality risk prediction. Methods: Olmsted County residents presenting with HF from July 2004 to September 2007 were prospectively recruited to undergo biomarker measurement. We investigated whether addition of CRP, BNP, and TnT to a model including established risk indicators improved 6-month mortality risk prediction using multiple methods ( c statistic, net reclassification index, integrated discrimination improvement). Results: Of 566 participants (mean age 77±13 years, 48% male), 87(15%) patients died after 6 months follow-up. Patients with CRP (<12.1mg/L), BNP (<341pg/mL), and TnT (≥0.01ng/mL) below the median (n=112) had the lowest mortality (3%), those with one or two biomarkers above the median had intermediate mortality, and those with all biomarkers above the median (n=105) had markedly increased 6-month mortality (33%). After adjustment for other predictors, higher CRP, BNP, and TnT were each associated with increased mortality, with odds ratios (95% confidence intervals) of 1.66(1.24 –2.24), 2.06(1.42–3.07), and 1.45(1.12–1.87), respectively. While adding CRP, BNP, and TnT individually to the model improved mortality risk prediction, the combination of two or more biomarkers offered greater incremental benefit. Using all biomarkers resulted in an increase in the c statistic from 0.747 to 0.832 (p<0.001), a net reclassification index of 0.33 (p<0.001), and a 100% relative improvement in risk discrimination (integrated discrimination improvement 0.097, p<0.001). Conclusions: The combined use of CRP, BNP, and TnT markedly improved the prediction of 6-month mortality in HF beyond established risk indicators. Implementation of a multimarker strategy including CRP, BNP, and TnT for risk prediction in HF should be considered. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).

Background: Contemporary data on survival after incident acute coronary syndrome (ACS), including both myocardial infarction (MI) and unstable angina (UA), are limited. Objective: To describe survival after incident ACS, to determine if it differs by ACS type (MI or UA) and to determine whether it has improved over time. Methods: Olmsted County, MN residents hospitalized between 1/1/2005-12/31/2010 were screened for incident ACS. ACS was defined as either MI validated by standard epidemiological criteria or UA validated by the Braunwald classification. Patients were followed for death from any cause. Cox proportional hazards regression was used to determine whether survival differed by ACS type, while adjusting for year of diagnosis, age, sex and comorbidities. Results: Among 1,160 incident ACS cases (mean±SD age 66.9±14.8, 60% male), 35% were UA and 65% were MI. After a mean (SD) follow up of 3.7 (2.1) years, 274 deaths occurred. The 3-year Kaplan-Meier survival estimate for MI was 79.6% (95% CI: 76.7%-82.6%) and for UA was 84.9% (95% CI: 81.3%-88.6%) (log-rank p=0.011). The association of ACS type with survival differed by age (p=0.056). After adjustment for year of diagnosis, sex and comorbidities, no difference in survival was observed between ACS types among those aged <60 (HR for MI vs. UA: 0.64, 95% 0.29-1.42). By contrast, among patients aged 60-79, those with an MI had 2 times the risk of death compared to those with UA (HR: 2.04, 95% CI: 1.24-3.37). Patients aged 80 or older who had an MI had a 40% increased risk of death compared to patients of the same age who had UA (HR: 1.42, 95% CI: 1.02-1.98). There was no difference in survival over time (HR for 2010 vs. 2005: 0.91, 95% CI: 0.61-1.36). Conclusions: Survival did not differ between UA and MI patients younger than 60, however among patients 60 or older, survival was worse among those with an MI. Survival after ACS did not change over the study period.

Background: A decline in all forms of coronary revascularization has been previously reported. Whether the decline has continued after the turn of the century is unknown as well as whether it is influenced by trends in the use and results of coronary angiography. Methods: All diagnostic and therapeutic coronary procedures performed among Olmsted County, MN residents from 2000-2015 were analyzed. Standardized rates (per 100,000 population) were calculated applying the direct method and temporal trends compared using Poisson regression models. Trends in disease severity, defined as 3-vessel and/or left main coronary artery disease (CAD), were assessed using logistic regression models. Results: Between 2000 and 2015, 11,691 coronary angiographies were performed (63% men; 54% ≥ 65 years of age). The age- and sex-standardized rates of angiography decreased over time (p trend < 0.001; Figure). Overall, 30% of the subjects had 3-vessel and/or left main CAD, and this proportion decreased over time (age- and sex-adjusted odds ratios (95% CI) for severe CAD: 0.68 (0.62-0.76) in 2005-2009 and 0.69 (0.63-0.77) in 2010-2015 compared with 2000-2004). Among 5,222 coronary revascularization procedures performed, 78% were PCI and 22% CABG. The age- and sex-standardized rates of any revascularization declined during the study period, reflecting temporal decreases in both PCI and CABG (all p trend < 0.001; Figure). The declines in angiography rates, CAD severity, and revascularization utilization were consistently greater in women than men (all P for interactions < 0.01). Conclusions: Declines in all forms of coronary revascularization, which were greater in women than men, have occurred in Olmsted County, MN, from 2000-2015. The declines occurred in the context of fewer angiograms performed in the population and reduced severity of anatomic CAD.

Background Temporal declines in cardiac stress tests results, coronary revascularization, and cardiovascular mortality have suggested a decline in the population burden of coronary disease until the 2000s. However, recent data indicate these favorable trends could be ending. We aimed to assess the evolution of the population burden of coronary disease in the community by examining trends in angiography and revascularization. Methods and Results We analyzed age‐ and sex‐adjusted trends from all coronary angiographic diagnostic procedures and revascularizations performed in Olmsted County, MN from 2000 to 2018. A total of 12 981 invasive angiograms were performed among 9049 individuals (64% men; 55% aged ≥65 years). Adjusted angiography rates decreased by 30% (95% CI , 25%–34%) between 2000 and 2009 and leveled off thereafter. Including computed tomography, angiography uncovered an increase in angiography use in recent years (risk ratio=1.15 [95% CI , 1.07–1.23] for 2018 versus 2014) and a decline in the prevalence of anatomic CAD from 2000 to 2018. CAD severity declined substantially from 2000 to 2009, followed by a plateau. Among 6570 revascularizations (72% men; 57% aged ≥65 years), 77% were percutaneous coronary interventions and 23% coronary artery bypass graft surgeries. The adjusted revascularization rates declined by 34% (95% CI , 27%–39%) from 2000 to 2009, followed by a plateau (risk ratio=1.10 [95% CI , 1.00–1.22]). Conclusions Between 2000 and 2018 in the community, coronary angiography use declined initially, leveled off, and then increased. Trends in CAD severity and revascularization use decreased then plateaued. The most recent trends are concerning as they suggest the burden of coronary disease is no longer declining. This warrants reinvigorated primary prevention and population surveillance.