Abstract
Background:
Polyvascular disease is associated with increased mortality and decreased quality of life. Whether its prevalence or associated outcomes differ for patients hospitalized with heart failure with reduced versus preserved ejection fraction (HFrEF vs. HFpEF, respectively) is uncertain.
Methods:
The Atherosclerosis Risk in Communities (ARIC) study conducted hospital surveillance of acute decompensated heart failure (ADHF) from 2005–2014. Polyvascular disease (coexisting disease in ≥2 arterial beds) was identified from prevalent coronary artery disease, peripheral artery disease, and cerebrovascular disease. Mortality risks associated with polyvascular disease were analyzed separately for HFpEF and HFrEF, with adjustment for potential confounders. All analyses were weighted by the inverse of the sampling probability.
Results:
Out of 24,937 weighted (5,460 unweighted) ADHF hospitalizations (52% female, 32% Black, mean age 75 years), polyvascular was prevalent in 22% with HFrEF and 17% with HFpEF. One-year mortality risks increased sequentially with 0, 1 and ≥2 arterial bed involvement, both for patients with HFrEF (29% to 32% to 38%; P-trend=0.0006) and HFpEF (26% to 32% to 37%; P-trend<0.0001). After adjustments, polyvascular disease was associated with a 26% higher mortality hazard for patients with HFrEF (HR=1.26; 95% CI: 1.07–1.50) and a 29% higher hazard for patients with HFpEF (HR =1.29; 95% CI: 1.03–1.62), with no interaction by HF type (P-interaction = 0.9).
Conclusion:
Patients hospitalized with ADHF and coexisting polyvascular disease have an increased risk of death, irrespective of HF type. Clinical attention should be directed toward polyvascular disease, with implementation of secondary prevention strategies to improve the prognosis of this high-risk population.
Summary:
Polyvascular disease is known to be associated with myocardial infarction, stroke or cardiovascular death and is a major risk factor for decreased quality of life. This study sought to evaluate the relationship between polyvascular disease and mortality in patients hospitalized with acute decompensated heart failure (ADHF), and to understand whether the associations differ based on ejection fraction. Patients hospitalized with ADHF and coexisting polyvascular disease had an increased risk of death, irrespective of heart failure type, implying the need for increased clinical attention directed towards polyvascular disease, along with implementation of secondary prevention strategies to improve prognosis.
Tweet:
Patients hospitalized with acute HF and coexisting polyvascular disease face an increased risk of death, irrespective of HF type.
Grphical Abstract
Introduction:
Polyvascular disease or presence of atherosclerosis in ≥2 arterial beds (1), is independently associated with heightened risk of myocardial infarction, ischemic stroke, and cardiovascular death (1,2). The presence of atherosclerosis in the peripheral or cerebral arteries is frequently associated with atherosclerotic involvement of the coronary arteries (3–12). In patients with heart failure with reduced ejection fraction (HFrEF), which often arises from ischemic etiology (13), concomittant peripheral artery disease has been associated with adverse cardiovascular events such as recurrent hospitalizations for acute decompensated heart failure (ADHF) (14). Less clinical focus has been directed toward atherosclerotic disease in patients with heart failure with preserved ejection fraction (HFpEF), nor is the prevalence of polyvascular disease in patients with HFpEF well characterized. However, evidence suggests that atherosclerotic risk factors, including age and diabetes mellitus, contribute towards a worse prognosis for patients with HFpEF (15). Reduced quality of life, high mortality, and substantial economic burden are important consequences of atherosclerotic disease, signifying the importance of primary and secondary intervention strategies (16–18) which may be particularly relevant to patients with HF. Importantly, the mortality rates are similarly high for HFrEF and HFpEF (19), warranting effective management of clinical risk factors which may contribute to adverse outcomes. In this study, we investigate the population prevalence and prognostic significance of polyvascular disease in patients with HFrEF and HFpEF who were hospitalized with ADHF.
Methods
The ARIC Study Data
The ARIC (Atherosclerosis Risk in Communities) study’s data are owned by the National Heart Lung and Blood Institute and are publicly available to qualified investigators with an approved manuscript proposal and data use agreement. The ARIC study includes a cohort population and several community surveillance populations (20); the present study is based on the HF community surveillance population.
The ARIC Study Community Surveillance
From 2005–2014, the ARIC study conducted community surveillance of hospitalized ADHF in Forsyth County, North Carolina; Washington County, Maryland; Jackson, Mississippi; and Minneapolis, Minnesota. As described, hospitalizations were randomly sampled within prespecified strata based on the ARIC community, discharge code (428.x or all other eligible codes), age (55–74, 75–84, or ≥85 years), sex, and race (Black or White) and reviewed by a physician panel (21). ADHF was differentiated from stable, chronic HF by evidence of new onset or worsening signs or symptoms of HF. All surveillance activities were approved by local institutional review boards. Patient consent was not required for surveillance because personal identifiers were redacted from the analytic dataset.
Data Abstraction
Demographic, clinical, and echocardiographic data were obtained from the medical record by certified abstractors following a standardized protocol. Ejection fraction was abstracted from in-hospital echocardiography reports and considered indicative of HFpEF when ≥50%. Medications typically prescribed for HF were recorded if administered during or prior to the hospitalization. Comorbid conditions were classified by presence or absence in the medical record. For the purposes of this analysis, obesity was defined by a body mass index ≥30 kg/m2, using the weight at hospital discharge. Renal disease was defined by hemodialysis use or an estimated glomerular filtration rate < 60 mL/min/1.73 m2, using the last abstracted serum creatine value from the hospital record and the CKD-Epi formula. Coronary artery disease was defined by clinical diagnosis of angina, significant coronary atherosclerosis, myocardial infarction, acute coronary syndrome, or history of coronary revascularization procedure (22,23). Peripheral artery disease was defined by clinical diagnosis of lower extremity artery disease, critical limb ischemia, claudication, or history of peripheral artery bypass surgery or percutaneous intervention. Cerebrovascular disease was defined by clinical diagnosis of stroke, transient ischemic attack, or reversible or partially reversible neurologic deficit. Consistent with previous studies, we considered ≥2 diagnoses of atherosclerotic disease (coronary artery disease, peripheral artery disease, and cerebrovascular disease) to be indicative of polyvascular disease, while involvement of one bed or fewer was characterized as non-polyvascular disease.
Outcomes
All-cause mortality outcomes within 28 days and 1 year of hospitalization were ascertained by the ARIC study, by linking hospital records with the National Death Index.
Statistical Analysis
All analyses were performed using SAS Survey Procedures 9.4 (SAS Institute; Cary, NC). Statistical tests and models accounted for the stratified sampling design and were weighted by the inverse of the sampling probability (24). Demographic and clinical characteristics were compared between patients with vs. without polyvascular disease, stratified by HF type. Continuous variables were assessed for normality and compared using the difference in least square means from weighted linear regression. Categorical variables were compared using Rao-Scott χ2 tests, with ordinal trends tested by logistic regression, using the Cochran-Armitage test for trend. Mortality outcomes at 28-days and 1-year of hospital admission were compared between patients with vs. without polyvascular disease by logistic and Cox regression, respectively, with stratification by HF type and adjustment for age, race, sex, year of admission, geographic region, length of stay (as a surrogate for hospitalization acuity), and comorbidities (smoking, diabetes mellitus, hypertension, and renal disease). Mortality hazards were also examined by incremental number (0, 1, 2+) of arterial beds with atherosclerotic involvement. We assessed potential modification of the association between polyvascular disease with mortality by constructing separate models stratified by HF type and various demographic subgroups, and by testing for multiplicative interaction.
Results:
From 2005–2014, a total of 23,409 eligible hospitalizations were sampled. Of these, 9,139 were identified as ADHF upon physician review. A total 247 patients with race other than White or Black were excluded, because the demographic stratum was too small for meaningful statistical analysis. After additionally excluding 461 with missing mortality outcomes, 8,453 (92% of those originally classified with ADHF) remained. Of these, 5460 (65%) had available echocardiography abstractions for classification of HFrEF and HFpEF. Applying the sampling weights yielded a weighted sample of 24,937 hospitalizations (Supplemental Figure 1). All subsequent results are presented with weighting by the sampling fraction.
Approximately half of our population was female (52%) and a third were Black (32%), with a mean age of 75 years. By comparison, the excluded patients without available echocardiography were on average 75 years old, 52% were women, and 29% were Black. Distributions of HFrEF and HFpEF in our study population were approximately equal (53% and 47%, respectively). The prevalence of atherosclerotic disease was higher for HFrEF than HFpEF hospitalizations, whether considering coronary artery disease (60% vs 47%), or to a lesser extent, cerebrovascular disease (20% vs 19%) or peripheral artery disease (13% vs 11%). The overall prevalence of polyvascular disease, defined by atherosclerotic disease at ≥2 arterial beds, was slightly higher for patients with HFrEF than HFpEF (22% vs. 17%; P <0.0001). The most common form of polyvascular disease was combined atherosclerotic involvement of the coronary and cerebral arteries, which was prevalent in 11% and 9% of patients with HFrEF and HFpEF respectively. Following this, the second most common form of polyvascular disease was combined atherosclerotic involvement of the coronary and peripheral arteries (Figure 1). Combined atherosclerotic involvement of all 3 vascular territories was rare, both for HFrEF and HFpEF, as was combined atherosclerotic involvement of the cerebral and peripheral arteries in the absence of coronary artery disease.
Figure 1:
Prevalence of polyvascular disease among patients hospitalized with acute decompensated heart failure, stratified by heart failure type. The community surveillance component of the Atherosclerosis Risk in Communities Study, 2005–2014.
Patients with HFrEF and polyvascular disease were slightly older (75 vs. 74 years), more often male (63% vs. 56%) and more frequently White (70% vs. 63%) than those with single or no arterial involvement. Among those with HFpEF, the mean age and sex distributions did not significantly differ by polyvascular disease; however, similar to patients with HFrEF, those with HFpEF and polyvascular disease were more often White (76% vs. 71%), Table 1. Diabetes mellitus was more prevalent with polyvascular disease for both HF types; however, history of hypertension, smoking, and renal disease only differed by polyvascular disease status among those with HFrEF. For both HF types, patients with polyvascular disease were more often administered beta blockers, lipid lowering agents and nitrates, compared with those without polyvascular disease. However, prescription of lipid lowering agents for patients with polyvascular disease was fairly low, both for those with HFrEF (68%) and HFpEF (62%). Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (ACEi / ARBs) were more often prescribed for patients with polyvascular disease than those without, but only among patients with HFrEF.
Table 1:
Demographic and clinical characteristics of patients hospitalized with acute decompensated heart failure, stratified by heart failure type and presence of polyvascular disease. The community surveillance component of the Atherosclerosis Risk in Communities Study, 2005–2014.
| Characteristic |
HFrEF
|
HFpEF
|
||||
|---|---|---|---|---|---|---|
| Polyvascular Disease N=2,916 |
No Polyvascular Disease N=10,407 |
P-value | Polyvascular Disease N=1,976 |
No Polyvascular Disease N=9,638 |
P-value | |
| Demographics | ||||||
| Age (mean ± SEM) | 75 ± 0.4 | 74 ± 0.3 | 0.01 | 77 ± 0.6 | 76 ± 0.3 | 0.2 |
| Male | 1850 (63%) | 5841 (56%) | 0.002 | 748 (38%) | 3397 (35%) | 0.4 |
| White | 2038 (70%) | 6586 (63%) | 0.002 | 1496 (76%) | 6806 (71%) | 0.03 |
|
| ||||||
| Clinical | ||||||
| Coronary artery disease | 2831 (97%) | 5135 (49%) | <0.0001 | 1838 (93%) | 3566 (37%) | <0.0001 |
| Myocardial infarction | 1535 (53%) | 2605 (25%) | <0.0001 | 780 (39%) | 1269 (13%) | <0.0001 |
| Peripheral artery disease | 1515 (52%) | 270 (3%) | <0.0001 | 960 (49%) | 293 (3%) | <0.0001 |
| Cerebrovascular disease | 1900 (65%) | 711 (7%) | <0.0001 | 1386 (70%) | 873 (9%) | <0.0001 |
| Obesity* | 736 (28%) | 2990 (32%) | 0.1 | 832 (47%) | 3988 (46%) | 0.8 |
| Smoking | 557 (19%) | 1579 (15%) | 0.02 | 230 (12%) | 1076 (11%) | 0.8 |
| Diabetes mellitus | 1637 (56%) | 4588 (44%) | <0.0001 | 1176 (60%) | 4338 (45%) | <0.0001 |
| Hypertension | 2631 (90%) | 8721 (84%) | 0.0004 | 1814 (92%) | 8437 (88%) | 0.06 |
| Renal disease † | 1891 (85%) | 6409 (80%) | 0.007 | 1321 (85%) | 5991 (82%) | 0.2 |
|
| ||||||
| Prior Procedures | ||||||
| Coronary artery bypass graft | 1254 (43%) | 1812 (17%) | <0.0001 | 606 (31%) | 1172 (12%) | <0.0001 |
| Percutaneous coronary intervention | 869 (30%) | 1679 (16%) | <0.0001 | 553 (28%) | 1021 (11%) | <0.0001 |
|
| ||||||
| Medications | ||||||
| ACEi / ARB | 1607 (55%) | 4871 (47%) | 0.0006 | 896 (46%) | 4387 (46%) | 0.9 |
| Beta blocker | 2249 (71%) | 6315 (61%) | <0.0001 | 1391 (71%) | 6073 (63%) | 0.006 |
| Lipid lowering | 1989 (68%) | 4893 (47%) | <0.0001 | 1230 (62%) | 4500 (47%) | <0.0001 |
| Nitrates | 1310 (45%) | 2709 (26%) | <0.0001 | 812 (41%) | 1823 (19%) | <0.0001 |
Abbreviations: HFrEF = heart failure with reduced ejection fraction, HFpEF = heart failure with preserved ejection fraction, SEM = standard error of the mean, ACEi / ARB = angiotensin converting enzyme inhibitor / angiotensin II receptor blocker
Obesity defined by body mass index ≥30 kg/m2, using the weight at hospital discharge. Obesity missing for 2576 patients.
Renal disease defined by receipt of hemodialysis or estimated glomerular filtration rate <60 mL/min/1.73 m2, using serum creatinine from the hospital visit and the CKD-Epi formula. Serum creatinine not abstracted in 2014 and missing for 5828 patients.
Overall, there were 1470 (11%) and 4291 (32%) deaths within 28-days and 1-year of hospitalization for patients with HFrEF, respectively, and 1106 (10%) and 3386 (29%) deaths within 28-days and 1-year of hospitalization for patients with HFpEF, respectively. Short-term mortality within 28 days of hospitalization was relatively stable by number of arterial beds with atherosclerotic involvement (0, 1 and ≥2 vascular territories), both for HFrEF (12% to 11% to 11%) and HFpEF (8% to 11% to 10%). However, when considering long-term outcomes, there was a stepwise increase in 1-year mortality with increasing number of arterial beds with atherosclerotic involvement, both for patients with HFrEF (29% to 32% to 38%; P-trend=0.0006) and HFpEF (26% to 32% to 37%); P-trend<0.0001, Figure 2. When compared with atherosclerotic involvement at 0 or 1 vascular territories, polyvascular disease (≥2 vascular territories) was associated with increased mortality for both HF types (Figure 3). When limiting the analysis to the subset of patients with CAD, the 1-year mortality risk tended to be higher for patients with polyvascular disease compared to CAD alone, both for patients with HFrEF (38% vs 30%; P=0.003) and HFpEF (36% vs. 31%, P = 0.09).
Figure 2:
Mortality risks associated with incremental number of arterial beds with atherosclerotic involvement in patients hospitalized with acute decompensated heart failure. The community surveillance component of the Atherosclerosis Risk in Communities Study, 2005–2014.
Figure 3:
Mortality hazards associated with polyvascular (≥2 arterial beds) vs. single or no arterial bed involvement in patients hospitalized with acute decompensated heart failure, stratified by heart failure type. The community surveillance component of the Atherosclerosis Risk in Communities Study, 2005–2014.
After full adjustments, polyvascular disease was associated with a 26% higher hazard of 1-year mortality in patients with HFrEF (HR=1.26; 95% CI: 1.07–1.50) and a 29% higher hazard in patients with HFpEF (HR =1.29; 95% CI: 1.03–1.62), with no significant interaction by HF type (P-interaction = 0.9), Table 2. These associations were largely unchanged by additional adjustment for lipid lowering therapies, both for HFrEF (HR = 1.29; 95% CI: 1.09 – 1.54) and HFpEF (HR = 1.33; 95% CI: 1.05 – 1.67). When examining mortality by number (0 to 1 to ≥2) of vascular territories with atherosclerotic involvement, mortality hazards increased with each increment in number of vascular beds, both for HFrEF (HR=1.11; 95% CI: 1.01–1.22) and HFpEF (HR=1.20; 95% CI: 1.07–1.36); P for interaction = 0.4 (Table 2).
Table 2:
Adjusted hazard ratios of mortality within 1 year of acute decompensated heart failure hospitalization, in association with polyvascular disease and incremental number of vascular beds with atherosclerotic disease. The community surveillance component of the Atherosclerosis Risk in Communities Study, 2005–2014.
| Mortality Risk Models |
HFrEF HR (95% CI) |
HFpEF HR (95% CI) |
|---|---|---|
| Polyvascular Disease vs. No Polyvascular Disease | ||
|
| ||
| Crude | 1.28 (1.10 – 1.49) | 1.34 (1.10 – 1.64) |
| Demographics* | 1.23 (1.05 – 1.43) | 1.32 (1.08 – 1.61) |
| Demographics, length of stay | 1.24 (1.06 – 1.44) | 1.33 (1.09 – 1.62) |
| Demographics, length of stay, comorbidities† | 1.26 (1.07 – 1.50) | 1.29 (1.03 – 1.62) |
|
| ||
| Per Increment in Number of Vascular Beds with Disease | ||
|
| ||
| Crude | 1.13 (1.04 – 1.23) | 1.24 (1.12 – 1.36) |
| Demographics* | 1.10 (1.01 – 1.20) | 1.21 (1.09 – 1.34) |
| Demographics, length of stay | 1.10 (1.01 – 1.20) | 1.21 (1.09 – 1.34) |
| Demographics, length of stay, comorbidities† | 1.11 (1.01 – 1.22) | 1.20 (1.07 – 1.36) |
Abbreviations: HFrEF = heart failure with reduced ejection fraction, HFpEF = heart failure with preserved ejection fraction
Demographics = age, race, sex, geographic region (Forsyth County, NC; Jackson, MS; Minneapolis, MN; Washington County, MD), and year of admission
Comorbidities = smoking, diabetes mellitus, hypertension, and renal disease
We also examined the HF-specific 1-year mortality risks associated with polyvascular disease by demographic subgroups. Among patients with HFrEF, polyvascular disease was similarly associated with mortality for Black and White patients, but when stratified by sex was only associated with mortality in men, and when stratified by age, was only associated with mortality for patients <75 years. In contrast, associations of polyvascular disease with 1-year mortality were similar for patients with HFpEF, irrespective of sex, race, or age (Figure 4).
Figure 4:
Adjusted* association of polyvascular disease with mortality within one year of hospitalization for acute decompensated heart failure, stratified by heart failure type and various subgroups. The community surveillance component of the Atherosclerosis Risk in Communities Study, 2005–2014.
*Models adjusted for age, race, sex, year of admission, geographic region, smoking, diabetes mellitus, hypertension, and renal disease
Discussion
In this large, population-based community surveillance of patients hospitalized with ADHF, we observed that the prevalence of polyvascular disease was fairly comparable for patients with HFrEF and HFpEF. We also note that polyvascular disease was associated with higher prevalence of cardiovascular and cardiometabolic comorbidities, higher use of evidence-based therapies and lipid lowering drugs, and increased history of invasive coronary interventions. Our study also confirms that polyvascular disease was associated with worse survival for both HF types, with all-cause mortality significantly higher with increasing number of vascular beds with atherosclerotic involvement.
The prevalence and prognosis of polyvascular disease in patients with ADHF has not been previously reported in a large-scale, population-based study. However, previous registries of systemic atherothrombosis, which primarily enrolled patients with established coronary or cerebrovascular disease, have reported a higher risk of cardiovascular events and death associated with polyvascular disease (4,25–27). For example, the REACH (Reduction in Atherothrombosis for Continued Health) registry reported a 15% prevalence of polyvascular disease in stable outpatients with atherothrombosis or multiple risk factors for atherothrombosis (4). A higher risk of major cardiovascular events was observed with polyvascular disease compared with single vascular territory disease, and the event rates increased with the number of arterial disease locations (2,28). Patients with established arterial disease also experienced higher event rates than patients with multiple risk factors, signifying the need for distinction between primary and secondary prevention (29). However, to date, less focus has been directed toward the prevalence and prognostic significance of polyvascular disease in HF populations.
In our study population of patients hospitalized with ADHF, patients with polyvascular disease were more often prescribed beta blockers, lipid lowering agents and nitrates, and more often had history of prior coronary revascularization procedures. Contrary to these findings and despite their higher risk profiles, patients with polyvascular disease have been reported to have a lower likelihood of receiving evidence-based therapies (1). The REACH registry demonstrated a substantial gap between actual clinical practices and recommended clinical guidelines for management of patients with or at risk for atherothrombosis. Similarly, in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation Of The ACC/AHA Guidelines) registry, which enrolled patients hospitalized with non ST-segment myocardial infarction, a pattern of underutilization of established medical therapies and lifestyle interventions was noted, throughout all vascular disease subtypes (4). Similarly, patients with prior vascular disease who presented with acute coronary syndrome were less likely to receive lipid-lowering therapy, smoking cessation counseling, and angiotensin-converting enzyme inhibitors (12). Statins have shown benefit in some, but not all, investigations of patients with HF (30–32), with the general consensus that they should not be prescribed for HF alone in the absence of another compelling indication for use. However, the administration of lipid lowering medications was notably low for patients in our study population with polyvascular disease, an established indication for statins, both among those with HFrEF and HFpEF (68% and 62%, respectively). Statins are well tolerated, widely available and inexpensive, and are thus an integral part of comprehensive comorbid HF and atherosclerotic cardiovascular disease management, particularly for patients with polyvascular disease.
Coronary artery disease is known to worsen the prognosis for patients with HF (19,33,34), and among our study population, was prevalent in 97% and 93% of patients with polyvascular disease, with respect to HFrEF and HFpEF. We noted that polyvascular disease most commonly presented as combined atherosclerotic involvement of the coronary and cerebral arteries, followed by combined involvement of the coronary and peripheral arteries. For both HF types, diabetes mellitus was more common with polyvascular disease. Although patients with polyvascular disease and coexisting diabetes mellitus are known to have increased cardiovascular risk (11,35–37), in our population of patients with ADHF, polyvascular disease remained associated with heightened mortality after adjustments for cardiovascular risk factors and cardiometabolic comorbidities. Importantly, the associated mortality risk did not significantly differ by HF type. Consistent with our results, a small, hospital-based registry reported worse prognosis of polyvascular disease for patients with HFpEF when compared with those with disease of single vascular territory (38). Taken together, these results highlight the need for risk factor modification or aggressive medical therapy for patients with HF and concomitant polyvascular disease and have important implications for designing large-scale preventive intervention trials. Additionally, increased awareness of the risk associated with the overlap between the various arterial locations of atherothrombosis could help improve the prognosis for such patients.
While HF guidelines currently focus on prevention of worsening HF events, death, and quality of life, (39) less attention is offered to secondary prevention of atherosclerotic cardiovascular disease, likely due to perception of competing risks and uncertainty about the benefits of specific prevention therapies. Furthermore, although statins are currently not recommended when used for HF alone (class IIIA), they are strongly recommended for HF prevention in those with history of myocardial infarction or acute coronary syndrome (class IA). Importantly, little guidance is offered regarding the role of statin therapy in patients with coexisting HF and atherosclerotic cardiovascular disease. However, with hopeful improvement in life expectancy and implementation of guideline directed medical therapy, broader rather than targeted prevention strategies may become more important among survivors.
Our study has certain limitations that merit discussion. Longitudinal outcomes other than vital status were not available in the community surveillance component of the ARIC study, and we were unable to consider subsequent clinical events such as rehospitalizations. Our study population was sampled from 4 US communities and restricted to individuals ≥55 years of age, and therefore may not represent the total US population of patients hospitalized with ADHF. It is also possible that treatment patterns for statins have increased since the time period of our study, which ended in 2014. Further, our analysis was limited to available data abstracted from the medical record and did not include data on antiplatelet therapies. We relied upon clinical definitions of vascular disease including symptomatic peripheral artery disease and cerebrovascular disease, because screening tests such as ankle-brachial index and carotid duplex were not widely available for asymptomatic patients, nor were they abstracted by the ARIC study. Additionally, the etiology of heart failure subtypes and the cause of death information were not collected by the ARIC study. However, the ARIC study Community Surveillance also has several important strengths. These include the large sample of patients with clinically adjudicated ADHF subtyped by HFrEF and HFpEF, standardized medical record abstractions, and ascertainment of mortality outcomes from the National Death Index.
In conclusion, patients hospitalized with ADHF and coexisting polyvascular disease have an increased risk of death, irrespective of HF type compared with those without polyvascular disease. Clinical attention should be directed toward polyvascular disease, with enactment of lifestyle modifications and secondary prevention strategies to improve the prognosis of this vulnerable population.
Supplementary Material
3 points:
Polyvascular disease was associated with higher prevalence of cardiovascular and cardiometabolic comorbidities, higher use of evidence-based therapies, and increased history of invasive coronary interventions.
Polyvascular disease was associated with worse survival for both HF types, with all-cause mortality significantly higher with increasing number of vascular beds with atherosclerotic involvement.
Future studies are needed to evaluate whether lifestyle modifications and secondary prevention strategies directed towards polyvascular disease can improve the prognosis of this vulnerable population.
Acknowledgments
Drs. Chunawala and Caughey conceptualized the study and wrote the manuscript. Dr. Caughey performed the statistical analysis. Drs. Qamar, Arora, Pandey, Fudim, Vaduganathan, Bhatt, and Mentz interpreted the data and revised the manuscript critically. The authors thank the staff and participants of the ARIC study for their important contributions.
Funding
The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract numbers (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, HHSN268201700005I).
Abbreviations
- ARIC
Atherosclerosis Risk in Communities Study
- ADHF
acute decompensated heart failure
- HF
heart failure
- HFpEF
heart failure with preserved ejection fraction
- HFrEF
heart failure with reduced ejection fraction
Footnotes
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Disclosures
RJM received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll.
MF was supported by NHLBI K23HL151744 from the National Heart, Lung, and Blood Institute (NHLBI), the American Heart Association grant No 20IPA35310955, Mario Family Award, Duke Chair’s Award, Translating Duke Health Award, Bayer and BTG Specialty Pharmaceuticals. He receives consulting fees from AxonTherapies, Bodyport, CVRx, Daxor, Edwards LifeSciences, Fire1, NXT Biomedical, Zoll, Viscardia.
MV has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Relypsa, and Roche Diagnostics, speaker engagements with Novartis and Roche Diagnostics, and participates on clinical endpoint committees for studies sponsored by Galmed and Novartis.
DLB discloses the following relationships - Advisory Board: Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Novartis, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, Svelte; Trustee:
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