Roger, Véronique L.

Background: We recently developed an index of socioeconomic status (SES) termed HOUSES ( HOU sing-based index of S ocio E conomic S tatus) to overcome the absence of SES measures in common data sources. HOUSES has been associated with various childhood health outcomes to a similar extent as other measures of SES. Whether it is associated with outcomes in adults is unknown. To address this question, we assessed whether HOUSES was associated with mortality after MI. Methods: We conducted a population-based cohort study among all Olmsted County, MN residents with MI who were prospectively identified using predetermined criteria from November 1, 2002 to May 31, 2006. HOUSES was formulated based on a z-score for housing value, actual square footage, and numbers of bedrooms and bathrooms and categorized into quartiles. The 1-year mortality rate post MI was compared among subjects with different SES by HOUSES based on a log-rank test. Results: Among 696 patients with MI; 623 (90%) were successfully geo-coded to address and real property data. Of these 623 subjects, 594 (95%) were white and 263 (42%) female; the mean age was 68±15 years. Spearman correlation coefficient between HOUSES and education level was 0.23 (p<0.001). Mortality rates at 1 year following MI were 20% (95%CI: 13 - 26), 18% (11 - 24), 14% (8 - 19), and 16% (10 - 21) for patients in the first (lowest SES), second, third, and fourth quartiles (highest SES) of the HOUSES index, respectively (p=0.032). This association between HOUSES and mortality after MI was primarily explained by age and comorbid conditions which were associated with HOUSES. Cardioprotective drugs such as aspirin, beta-blocker, and statins were not associated with HOUSES nor accounted for the association between HOUSES and mortality after MI. Conclusions: Despite the lack of a strong correlation with other SES measure (i.e. no redundancy), HOUSES may be useful for overcoming the paucity of conventional SES measures in commonly used datasets in epidemiological research concerning cardiovascular disease among adults.

Background: Acute aortic syndrome (AAS) includes aortic dissection (AD), intramural hematoma (IMH) and penetrating aortic ulcer (PAU) and confers high rates of aortic related events. However, the risk of cardiovascular (CV) events in this patient group is unknown. The aim of this study was to define the rates of CV events in an incident cohort of AAS patients. Methods: Medical records and death certificates of all Olmsted County, MN residents with a diagnosis of AAS from 1995-2015 were reviewed and compared to age- and sex- matched population controls. Primary outcome was non-aortic CV mortality. Secondary outcome was overall mortality and first time non-fatal CV event (myocardial infarction (MI), heart failure (HF) or stroke). Events were analyzed using Cox proportional hazards regression adjusting for comorbidities. Results: Of 133 patients with AAS (77 AD, 21 IMH, 35 PAU) 57% were male, median age was 72 (SD 14) and median follow-up was 10 years. Overall survival in AAS cases and controls was 62% versus 83% at 5 years and 44% versus 60% at 10 years (adj HR 1.8, p<.001, 95% CI 1.3-2.4). CV death occurred in 21 (29%) of 73 AAS decedents due to HF (9), MI (5), other cardiac causes (5), stroke (1) and peripheral vascular disease (1). CV-related survival at 5 and 10 years after AAS diagnosis (91% and 81%) was not significantly different from controls (95% and 86%) after adjustment for comorbidities (adj HR 1.8, p=.1, 95% CI 0.9-3.6). AAS was associated with an increased risk of any first time CV event (adj HR 2.6, p<.001, 95% CI 1.6-4.4; Figure), first time diagnosis of MI (adj HR 2.8, p<.001, 95% CI 1.7-4.7) and HF (adj HR 3.2, p<.001, 95% CI 1.6-6.2) but not stroke. When excluding acute events within 14 days of diagnosis, AAS was still associated with a significantly higher mortality (adj HR 1.6, p=.011, 95% CI 1.1-2.4) and an increased risk of any first time CV event (adj HR 2.2, p=.018, 95% CI 1.1-4.1), first time MI (adj HR 2.2, p=.012, 95% CI 1.2-4.1) and HF (adj HR 2.9, p=.006, 95% CI 1.4-6.2) but not stroke. Conclusions: AAS is associated with a higher overall mortality and an increased risk of any first time CV event, first time MI and HF that persists beyond the acute phase. These data highlight the risk of CV events among those with AAS and implicate the need for long-term cardiovascular management in these patients.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia in current clinical practice. Yet, contemporary community data on adverse outcomes, such as ischemic stroke (IS) and heart failure (HF), are scarce. Methods: We assembled a community-based cohort of incident AF among Olmsted County, MN residents ≥18 years of age from 2000-2010. IS, transient ischemic attack (TIA), and incident HF occurring through 12/31/2012 were identified using diagnosis codes and were manually validated. Cox proportional hazards regression was used to determine age- and sex-adjusted predictors of IS/TIA and HF, as well as the association of year of AF diagnosis with these outcomes after adjustment for demographics and comorbidities. Results: Among 3315 incident AF (mean age 72.6 years, 52% male), 346 (10%) developed a subsequent IS (n=230) or TIA (n=116) over a mean follow-up of 4.2 years. In the 2807 AF patients without prior HF, 782 (28%) developed HF over a mean of 3.9 years. Differences in the predictors of subsequent IS/TIA and HF were observed (Figure). Increasing age, female sex, and prior IS/TIA were associated with an increased risk of IS/TIA, whereas increasing age, obesity, smoking, prior myocardial infarction, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, prior IS/TIA, and renal disease predicted the development of HF after AF. The risk of subsequent IS/TIA or HF did not differ by year of AF diagnosis. Compared to those diagnosed with AF in 2000-2003, the adjusted hazard ratios (HR) (95% CI) for ischemic IS/TIA were 0.84 (0.65-1.08) and 1.02 (0.76-1.36) for those diagnosed with AF in 2004-2007 and 2008-2010, respectively (P time trend =0.58); similar results were observed for IS alone. The corresponding HRs for HF were 0.99 (0.83-1.16) and 0.93 (0.76-1.13) for those diagnosed with AF in 2004-2007 and 2008-2010 compared to 2000-2003 (P time trend =0.43). Conclusions: In the community, adverse outcomes are frequent after AF, and HF occurs more frequently than IS/TIA. Risk factors differed for IS/TIA and HF, suggesting that pathways to the occurrence of these outcomes, as well as prevention strategies, may differ. Finally, the occurrence of these outcomes did not decline over the last decade, highlighting the importance of continued rigorous surveillance of adverse outcomes in AF.

Background: Several chronic diseases can contribute to functional disability. However, little is known about functional disability and its progression overtime in chronic heart failure (HF). We aimed to investigate the prevalence and progression of difficulty with activities of daily living (ADLs) and its association with mortality in patients with HF. Methods: We enrolled Southeastern Minnesota residents with HF into a longitudinal study from September 2, 2003 through January 31, 2012. A patient’s difficulty with 9 ADLs (feeding themselves, dressing, toileting, housekeeping, climbing stairs, bathing, walking, using transportation, managing medications) was assessed by questionnaire. Patients were followed for all-cause mortality. Using Rasch analysis to determine the order of ADL difficulty, patients were divided into 3 categories (minimal, moderate, severe difficulty). Predictors of ADL difficulty were assessed using negative binomial regression and the association between ADL difficulty and death with Cox proportional hazard regression. Results: Among 1128 patients (mean age 74.7 years, 49.2% female), most (59.4%) reported difficulty with one or more ADLs at enrollment, with 272 (24.1%) and 146 (12.9%) reporting moderate and severe difficulty, respectively. The independent predictors of difficulty with ADLs were older age, female sex, diabetes, morbid obesity, cerebrovascular disease, dementia, anemia, and unmarried status. After a mean (SD) follow-up of 3.2 (2.4) years, 615 (54.5%) patients had died. There was a stepwise increase in the risk of death as difficulty with ADLs increased ( Figure ). After adjusting for age, sex, and comorbidity, the HR (95% CI) for mortality was 1.52 (1.25-1.83, p<0.001) for patients with moderate and 2.28 (1.82-2.85, p<0.001) for those with severe difficulty with ADLs compared to those with minimal difficulty (p for trend<0.001). In most patients (73.5%), difficulty with ADLs was stable over time. However, survivors reporting persistently severe or worsening ADL difficulty in a second assessment (median 9 months later) were at an increased risk of subsequent mortality (adjusted HR 2.08, 95% CI 1.70-2.55, p<0.001). Conclusions: Functional disability is common in patients with HF, can progress over time, and is independently associated with adverse prognosis.

Background: Heart failure (HF) has an overall poor prognosis, with only half of patients surviving more than 5 years after diagnosis. Although it is recommended that all patients with HF have advance directives (ADs) in place before the end of life is imminent, the use of ADs in these patients has not been well studied. Methods: We prospectively enrolled all Olmsted County residents presenting with active HF from October 2007 through October 2011 into a longitudinal community cohort study which included an echocardiogram and administration of health status questionnaires at enrollment. Information from ADs completed prior to enrollment was manually abstracted from the patient’s medical record. Results: A total of 608 patients were enrolled during the study period (mean age 74.0 years, 54.9% male, 49.9% with preserved EF [EF≥50%], 65.3% NYHA functional class 3 or 4). Mortality was high; 164 (27.0%) patients died after a mean follow-up of 1.8 years with estimated 1-year mortality of 14.3%. At the time of enrollment, only 249 (41.0%) patients had ADs, and they were completed an average of 3.3 years prior. Although most ADs appointed a proxy decision-maker (91.1%), less than half addressed patient wishes regarding use of cardiopulmonary resuscitation (41.4%), mechanical ventilation (38.7%), administration of artificial nutrition (38.6%), or hemodialysis (10.0%) at the end of life. AD use was more common in older individuals (p<0.001); 60.7% of those ≥80 years had an AD vs. 13.6% of those who were <60 years old. While ADs were more common in women than men (46.7% vs. 36.2%, respectively) and in those with preserved EF (47.2% vs. 34.0% in those with reduced EF), differences were not significant after adjustment for age. AD use was no more common in patients with worse NYHA functional class or health status as measured by the Kansas City Cardiomyopathy Questionnaire. Conclusions: Despite a high mortality rate, over half of community patients with HF do not have ADs, and existing AD fail to address important medical decisions common at the end of life. Further work is needed to identify potential barriers to AD use in HF patients, and to determine whether their use has any impact on patient outcomes, including end of life resource utilization.

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.

The importance of coronary artery disease (CAD) surveillance, as recently underscored by the American Heart Association, is heightened by the obesity/diabetes epidemics. The need for surveillance is especially great for subclinical CAD, as the greatest increases in obesity/diabetes are occurring among younger age groups, where clinically-recognized CAD is infrequent. Yet few methods for such population-based surveillance exist. Using one such method, unbiased heart autopsy data, we previously showed that declines in grade of CAD observed since 1981 ended in the mid-1990s and may have reversed. In order to assess and interpret the factors underlying these observations, it is necessary to first examine trends in CAD risk factors among heart autopsied decedents and investigate the extent to which they mirror trends in the general population. Rochester Epidemiology Project (REP) medical records linkage resources were used to identify 1) all Olmsted County residents age 16-64 years who died from non-natural causes and went to autopsy 1981-2009 (96% autopsy rate) and 2) all Olmsted County residents age 16-64 years 1981-2009. We randomly selected two population subjects per decedent, stratified by calendar year. All REP inpatient/ ambulatory records were reviewed for CAD risk factors. Compared to population subjects, decedents were older and more likely to be male, smokers, alcohol abusers, and treated for hypertension; however, risk factor trends for both groups were generally of similar magnitude and direction, i.e., smoking, alcohol use, and blood pressure declined and anti-hypertensive medication use, diagnosed hyperlipidemia, and body mass index increased ( Table ). These population-based longitudinal data indicate that temporal trends in risk factors among autopsied decedents parallel those for the general population, supporting the concept that data on autopsied decedents can provide insight into trends in CAD risk and the changing burden of atherosclerosis within the source population. Characteristics of all 1) non-elderly adult Olmsted County residents who died non-natural deaths and were autopsied and 2) non-elderly adult Olmsted County residents with respect to CAD risk factors and calendar year trends CAD Risk Factor Autopsied Decedents (N=315) Population Subjects (N=672) P Value Autopsied Decedents, Temporal Trend Population Subjects, Temporal Trend N Calendar Year Estimate P value N Calendar Year Estimate P Value Age at Index, Mean (SD) 37.5 (14.0) 34.1 (13.6) <0.01 1 315 0.172 0.06 1 672 −0.059 0.33 1 Sex, % Male 236 (75%) 339 (50%) <0.01 2 315 0.008 0.60 2 672 −0.008 0.39 2 Race, % Non-White 29 (9%) 85 (13%) 0.14 3 305 0.054 0.04 3 589 0.023 0.12 3 Of Ever Smokers, Current = Yes 128/184 (70%) 118/210 (56%) 0.01 3 184 −0.040 0.048 3 210 −0.052 <0.01 3 Of Ever Alcohol Use, Current = Yes 175/238 (74%) 284/364 (78%) 0.08 3 238 −0.065 <0.01 3 364 −0.027 0.09 3 Mention of Alcoholism, Yes 80 (25%) 41 (6%) <0.01 3 315 0.014 0.35 3 672 0.042 0.04 3 Closest Systolic BP, Mean (SD) 124.1 (16.6) 120.3 (15.7) 0.34 3 285 −0.179 0.09 3 600 −0.156 0.02 3 Closest Diastolic BP, Mean (SD) 76.2 (11.6) 74.0 (10.5) 0.53 3 285 −0.194 0.01 3 600 −0.112 0.02 3 Closest BP on Medication, Yes 44 (14%) 36 (5%) <0.01 3 283 0.046 0.03 3 599 0.063 <0.01 3 Hyperlipidemia Diagnosis, Yes 32 (10%) 65 (10%) 0.32 3 315 0.114 <0.01 3 672 0.078 <0.01 3 Closest Fasting Glucose, Mean (SD) 95.8 (26.0) 95.0 (27.6) 0.63 3 177 0.270 0.23 3 335 0.505 <0.01 3 Closest BMI, Mean (SD) 26.1 (5.8) 25.9 (5.4) 0.52 3 280 0.080 0.04 3 593 0.091 <0.01 3 1 Unadjusted, Chi-square; 2 Unadjusted, Wilcoxon rank sum test; 3 Adjusted for age and sex, linear or logistic regression; BP = Blood Pressure; BMI = Body Mass Index

Background: Hospital readmissions are considered to be a quality of care indicator, yet little is known about their occurrence and predictors after myocardial infarction (MI) in the community. Methods: We identified all Olmsted County residents with incident MI from 1987-2007 and evaluated 30-day rehospitalizations. The reason for readmission was categorized based on ICD-9 code. Safety endpoints of revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or fibrinolysis included stroke, acute kidney injury (rise in creatinine post-procedure of >0.5 mg/dL), access site complication (PCI), and gastrointestinal or other bleeding. Cox proportional hazard regression models were used to examine the predictors of readmission. Results: A total of 2617 patients (mean age 67 years, 41% female) had incident MI (32% with ST-elevation) from 1987-2007 and survived their initial hospitalization. A total of 583 readmissions occurred within 30 days among 512 (19.6%) patients. Approximately half (n=286, 49.1%) of readmissions were due to cardiovascular causes, and of these, most were due to ischemic heart disease (n=175, 61.2%) or heart failure (n=56, 19.6%). The proportion of non-cardiovascular rehospitalizations increased over time, from 42.2% from 1993-97 to 59.4% from 2003-07 (p for trend=0.01). A minority of those readmitted for cardiovascular reasons required repeat angiogram (n=110, 38.5%) or revascularization (n=88, 50 PCI, 38 CABG). After adjustment for confounders, key factors were associated with increased rehospitalization risk ( Figure ). Following PCI (n=1230), a stroke or bleeding event (adjusted HR 1.69, 95% CI 1.09-2.61, p=0.02) and acute kidney injury (HR 2.50, 95% CI 1.61-3.87, p<0.01) were associated with markedly increased readmission risk. Conclusions: Half of readmissions within 30 days of MI are for non-cardiovascular reasons, and this proportion has increased. Comorbidity and complications of revascularization are key predictors of readmission.

Background: The goal of heart failure (HF) performance measures is to improve the quality of care by enabling the practice implementation of guidelines. The guidelines define the population eligible for each measure. Little is known about the proportion of eligible patients to which these measures are applicable in the community. Methods: We determined the eligibility for and the adherence to performance measures and beta-blocker therapy in a community-based cohort of hospitalized patients diagnosed with incident HF from January 2005 to April 2011. Results: Of 294 inpatients with first ever HF (mean age 72 ± 15 years, 48% men), ejection fraction was measured in 292 (99%) patients during hospitalization. Of these, 97 (33%) had an ejection fraction <40% and were thus candidates for beta-blocker and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB) therapy. After excluding individuals with absolute contraindications, 71 patients were eligible to receive ACE inhibitors or ARB, and 86 were eligible to receive beta-blockers (figure). Among those eligible, 83% received ACEI/ARB and 91% received beta-blockers. Excluding those with relative contraindications, 70 patients were eligible for beta-blockers and 90% of them received it. Among the 139 (47%) individuals with HF and atrial fibrillation, 35 were eligible for warfarin and 49% received it. Of the 36 current smokers, 22 (61%) received cessation counseling during hospitalization. Conclusions: In the community, among patients hospitalized with HF eligible for performance measures, the implementation of performance measures varies by measure and can be improved for some. However, most community HF patients are not eligible for performance measures and other approaches should be identified to improve their care and outcomes.