Multimorbidity Burden and Adverse Outcomes in a Community‐Based Cohort of Adults with Heart Failure

BACKGROUND Soluble ST2 (sST2) is a cardiac biomarker whose concentration rises in response to myocardial strain. Increased sST2 concentrations may predict adverse outcomes in patients with heart failure and myocardial infarction. Because sST2 was largely undetectable with first-generation assays in ambulatory individuals, there are few data regarding its distribution and correlates in community-based populations. METHODS We measured sST2 using a highly sensitive ELISA in 3450 Framingham Heart Study participants who attended a routine examination. We used multivariable linear regression models to identify covariates associated with sST2 in the general sample. We obtained a reference sample (n = 1136) by excluding individuals with prevalent coronary disease, heart failure, atrial fibrillation, diabetes, hypertension, obesity, valvular disease, left ventricular systolic dysfunction, and pulmonary and renal dysfunction. We used empiric and quantile regression techniques to estimate the 2.5th, 50th, 97.5th, and 99th quantiles. RESULTS In the general sample (mean age 59 years, 55% women), systolic blood pressure (P = 0.006), antihypertensive medication use (P = 0.03), and diabetes (P < 0.001) were associated with sST2 concentrations. In the reference sample (mean age 55, 59% women), male sex (P < 0.0001) and older age (P = 0.004) were predictive of higher sST2 concentrations. Quantile and empirical methods were used to define the reference intervals. Using the empirical approach, upper 99% percentile values in different age groups ranged from 46.6 to 64.4 μg/L in men and 36.7 to 53.0 μg/L in women. CONCLUSIONS In a well-characterized, community-based cohort, values for sST2 differ between men and women, increase with age, and are associated with diabetes and hypertension.

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Faculty Opinions recommendation of Temporal relationship and prognostic significance of atrial fibrillation in heart failure patients with preserved ejection fraction: a community-based study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718056194.793483548 ◽

2013 ◽

Author(s):

Gad Cotter ◽

Olga Milo

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Ejection Fraction ◽

Temporal Relationship ◽

Prognostic Significance ◽

Preserved Ejection Fraction ◽

Community Based ◽

Heart Failure Patients

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Faculty Opinions recommendation of Devices and interventions for the prevention of adverse outcomes of tachycardia on heart failure.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732657761.793571600 ◽

2020 ◽

Author(s):

Athanasios Manolis

Keyword(s):

Heart Failure ◽

Adverse Outcomes

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Diabetes and Heart Failure: Is it Hyperglycemia or Hyperinsulinemia?

Current Vascular Pharmacology ◽

10.2174/1570161117666190408164326 ◽

2020 ◽

Vol 18 (2) ◽

pp. 148-157 ◽

Cited By ~ 3

Author(s):

Triantafyllos Didangelos ◽

Konstantinos Kantartzis

Keyword(s):

Heart Failure ◽

Insulin Treatment ◽

Close Association ◽

Adverse Outcomes ◽

Negative Effects ◽

Beneficial Effects ◽

Appropriate Treatment ◽

Increased Risk ◽

Treatment Of Diabetes

The cardiac effects of exogenously administered insulin for the treatment of diabetes (DM) have recently attracted much attention. In particular, it has been questioned whether insulin is the appropriate treatment for patients with type 2 diabetes mellitus and heart failure. While several old and some new studies suggested that insulin treatment has beneficial effects on the heart, recent observational studies indicate associations of insulin treatment with an increased risk of developing or worsening of pre-existing heart failure and higher mortality rates. However, there is actually little evidence that the associations of insulin administration with any adverse outcomes are causal. On the other hand, insulin clearly causes weight gain and may also cause serious episodes of hypoglycemia. Moreover, excess of insulin (hyperinsulinemia), as often seen with the use of injected insulin, seems to predispose to inflammation, hypertension, dyslipidemia, atherosclerosis, heart failure, and arrhythmias. Nevertheless, it should be stressed that most of the data concerning the effects of insulin on cardiac function derive from in vitro studies with isolated animal hearts. Therefore, the relevance of the findings of such studies for humans should be considered with caution. In the present review, we summarize the existing data about the potential positive and negative effects of insulin on the heart and attempt to answer the question whether any adverse effects of insulin or the consequences of hyperglycemia are more important and may provide a better explanation of the close association of DM with heart failure.

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Abnormal Liver Function Tests and Long-Term Outcomes in Patients Discharged after Acute Heart Failure

Journal of Clinical Medicine ◽

10.3390/jcm10081730 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1730

Author(s):

Hiroshi Miyama ◽

Yasuyuki Shiraishi ◽

Shun Kohsaka ◽

Ayumi Goda ◽

Yosuke Nishihata ◽

...

Keyword(s):

Heart Failure ◽

Liver Function ◽

Liver Function Tests ◽

Abnormal Liver Function ◽

Adverse Outcomes ◽

Long Term Outcomes ◽

Function Tests ◽

Parameter Values

Abnormal liver function tests (LFTs) are known to be associated with impaired clinical outcomes in heart failure (HF) patients. However, this implication varies with each single LFT panel. We aim to evaluate the long-term outcomes of acute HF (AHF) patients by assessing multiple LFT panels in combination. From a prospective multicenter registry in Japan, 1158 AHF patients who were successfully discharged were analyzed (mean age, 73.9 ± 13.5 years; men, 58%). LFTs (i.e., total bilirubin, aspartate aminotransferase or alanine aminotransferase, and alkaline phosphatase) at discharge were assessed; borderline and abnormal LFTs were defined as 1 and ≥2 parameter values above the normal range, respectively. The primary endpoint was composite of all-cause death or HF readmission. At the time of discharge, 28.7% and 8.6% of patients showed borderline and abnormal LFTs, respectively. There were 196 (16.9%) deaths and 298 (25.7%) HF readmissions during a median 12.4-month follow-up period. The abnormal LFTs group had a significantly higher risk of experiencing the composite outcome (adjusted hazard ratio: 1.51, 95% confidence interval: 1.08–2.12, p = 0.017), whereas the borderline LFTs group was not associated with higher risk of adverse events when referenced to the normal LFTs group. Among AHF patients, the combined elevation of ≥2 LFT panels at discharge was associated with long-term adverse outcomes.

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Serum uric acid, influence of sacubitril/valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON-HF

European Heart Journal ◽

10.1093/ehjci/ehaa946.1066 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Selvaraj ◽

B.L Claggett ◽

D.V Veldhuisen ◽

I.S Anand ◽

B Pieske ◽

...

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Ejection Fraction ◽

Serum Uric Acid ◽

Primary Outcome ◽

Adverse Outcomes ◽

Funding Source ◽

Preserved Ejection Fraction ◽

Private Company ◽

Increased Risk

Abstract Background Serum uric acid (SUA) is a biomarker of several pathobiologies relevant to the pathogenesis of heart failure with preserved ejection fraction (HFpEF), though by itself may also worsen outcomes. In HF with reduced EF, SUA is independently associated with adverse outcomes and sacubitril/valsartan reduces SUA compared to enalapril. These effects in HFpEF have not been delineated. Purpose To determine the prognostic value of SUA, relationship of change in SUA to quality of life and outcomes, and influence of sacubitril/valsartan on SUA in HFpEF. Methods We analyzed 4,795 participants from the Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial. We related baseline hyperuricemia to the primary outcome (CV death and total HF hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 4-month visit, the relationship between SUA change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and several biomarkers including N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also assessed. We simultaneously adjusted for baseline and time-updated SUA to determine whether lowering SUA was associated with clinical benefit. Results Average age was 73±8 years and 52% were women. After multivariable adjustment, hyperuricemia was associated with increased risk for most outcomes (primary outcome HR 1.61, 95% CI 1.37, 1.90, Fig 1A). The treatment effect of sacubitril/valsartan for the primary outcome was not modified by baseline SUA (interaction p=0.11). Sacubitril/valsartan reduced SUA −0.38 mg/dL (95% CI: −0.45, −0.31) compared with valsartan (Fig 1B), with greater effect in those with baseline hyperuricemia (−0.50 mg/dL) (interaction p=0.013). Change in SUA was independently and inversely associated with change in KCCQ-OSS (p=0.019) and eGFR (p<0.001), but not NT-proBNP (p=0.52). Time-updated SUA was a stronger predictor of adverse outcomes over baseline SUA. Conclusions SUA independently predicts adverse outcomes in HFpEF. Sacubitril/valsartan significantly reduces SUA compared to valsartan, an effect that was stronger in those with higher baseline SUA, and reducing SUA was associated with improved outcomes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis

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