Abdominal Obesity Is Associated With an Increased Risk of All-Cause Mortality in Patients With HFpEF

Tsujimoto, Tetsuro; Kajio, Hiroshi

doi:10.1016/j.jacc.2017.09.1111

Cited by 169 publications

(140 citation statements)

References 44 publications

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“…Recent studies have identified distinct high‐risk clinical phenotypes in patients with HF . Specifically, the ‘obesity phenotype’ has been associated with greater impairments in cardiac structure and function, worse symptom burden, and higher risk of HF hospitalization . In a recent analysis from the TOPCAT trial cohort, abdominal obesity was associated with significantly higher risk of adverse events among patients with HFpEF with no significant interaction between spironolactone use and abdominal obesity .…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, the ‘obesity phenotype’ has been associated with greater impairments in cardiac structure and function, worse symptom burden, and higher risk of HF hospitalization . In a recent analysis from the TOPCAT trial cohort, abdominal obesity was associated with significantly higher risk of adverse events among patients with HFpEF with no significant interaction between spironolactone use and abdominal obesity . Similarly, the ‘diabetes phenotype’ in patients with HFpEF has also been associated with higher symptom burden and greater risk of adverse outcomes .…”

Section: Discussionmentioning

confidence: 99%

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Phenomapping of patients with heart failure with preserved ejection fraction using machine learning‐based unsupervised cluster analysis

Segar

Patel

Ayers

et al. 2019

European J of Heart Fail

186

206

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Aim To identify distinct phenotypic subgroups in a highly‐dimensional, mixed‐data cohort of individuals with heart failure (HF) with preserved ejection fraction (HFpEF) using unsupervised clustering analysis. Methods and results The study included all Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) participants from the Americas (n = 1767). In the subset of participants with available echocardiographic data (derivation cohort, n = 654), we characterized three mutually exclusive phenogroups of HFpEF participants using penalized finite mixture model‐based clustering analysis on 61 mixed‐data phenotypic variables. Phenogroup 1 had higher burden of co‐morbidities, natriuretic peptides, and abnormalities in left ventricular structure and function; phenogroup 2 had lower prevalence of cardiovascular and non‐cardiac co‐morbidities but higher burden of diastolic dysfunction; and phenogroup 3 had lower natriuretic peptide levels, intermediate co‐morbidity burden, and the most favourable diastolic function profile. In adjusted Cox models, participants in phenogroup 1 (vs. phenogroup 3) had significantly higher risk for all adverse clinical events including the primary composite endpoint, all‐cause mortality, and HF hospitalization. Phenogroup 2 (vs. phenogroup 3) was significantly associated with higher risk of HF hospitalization but a lower risk of atherosclerotic event (myocardial infarction, stroke, or cardiovascular death), and comparable risk of mortality. Similar patterns of association were also observed in the non‐echocardiographic TOPCAT cohort (internal validation cohort, n = 1113) and an external cohort of patients with HFpEF [Phosphodiesterase‐5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial cohort, n = 198], with the highest risk of adverse outcome noted in phenogroup 1 participants. Conclusions Machine learning‐based cluster analysis can identify phenogroups of patients with HFpEF with distinct clinical characteristics and long‐term outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Phenomapping of patients with heart failure with preserved ejection fraction using machine learning‐based unsupervised cluster analysis

Segar

Patel

Ayers

et al. 2019

European J of Heart Fail

186

206

View full text Add to dashboard Cite

show abstract

“…Both obesity and type 2 diabetes are important risk factors for the development of heart failure (HF) with preserved ejection fraction (HFpEF) . Of patients with established HFpEF, 70–80% are obese, and nearly half have type 2 diabetes . However, the diagnosis of HFpEF can be challenging.…”

Section: Introductionmentioning

confidence: 99%

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Packer

2019

European J of Heart Fail

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Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk‐to‐benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post‐ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients.

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“…Some investigators contend that HFpEF, in obesity, may even be a distinct form of heart failure that may require specific treatment . Furthermore, abdominal obesity is associated with an increased mortality in patients with HFpEF . Amongst many of its characteristics, obesity has been viewed as a hypoxic state .…”

Section: Introductionmentioning

confidence: 99%

Hypoxia‐inducible factor 1‐alpha (HIF‐1α) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction

Warbrick

Rabkin

2019

Obesity Reviews

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Summary Heart failure with preserved ejection fraction (HFpEF), a common condition with an increased mortality, is strongly associated with obesity and the metabolic syndrome. The latter two conditions are associated with increased epicardial fat that can extend into the heart. This review advances the proposition that hypoxia‐inhibitory factor‐1α (HIF‐1α) maybe a key factor producing HFpEF. HIF‐1α, a highly conserved transcription factor that plays a key role in tissue response to hypoxia, is increased in adipose tissue in obesity. Increased HIF‐1α expression leads to expression of a potent profibrotic transcriptional programme involving collagen I, III, IV, TIMP, and lysyl oxidase. The net effect is the formation of collagen fibres leading to fibrosis. HIF‐1α is also responsible for recruiting M1 macrophages that mediate obesity‐associated inflammation, releasing IL‐6, MCP‐1, TNF‐α, and IL‐1β with increased expression of thrombospondin, pro α2 (I) collagen, transforming growth factor β, NADPH oxidase, and connective tissue growth factor. These factors can accelerate cardiac fibrosis and impair cardiac diastolic function. Inhibition of HIF‐1α expression in adipose tissue of mice fed a high‐fat diet suppressed fibrosis and reduces inflammation in adipose tissue. Delineation of the role played by HIF‐1α in obesity‐associated HFpEF may lead to new potential therapies.

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Abdominal Obesity Is Associated With an Increased Risk of All-Cause Mortality in Patients With HFpEF

Abstract: The risk of all-cause mortality was significantly higher in patients with HFpEF with abdominal obesity than in those without abdominal obesity.

Cited by 169 publications

References 44 publications

Phenomapping of patients with heart failure with preserved ejection fraction using machine learning‐based unsupervised cluster analysis

Phenomapping of patients with heart failure with preserved ejection fraction using machine learning‐based unsupervised cluster analysis

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Hypoxia‐inducible factor 1‐alpha (HIF‐1α) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction

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