Obesity and the paradox of mortality and heart failure hospitalization in heart failure with preserved ejection fraction

Mandviwala, Taher; Basra, Sukhdeep S.; Khalid, Umair; Pickett, June K.; Przybylowicz, Ryle; Shah, Tina; Nambi, Vijay; Virani, Salim S.; Deswal, Anita

doi:10.1038/s41366-020-0563-1

Cited by 32 publications

(19 citation statements)

References 35 publications

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“…Akintoye and colleagues also reported a significant association of CCI with in‐hospital mortality, but there has been no distinction between elective and non‐elective hospital admission in their study 41 . Obesity was associated with a reduced in‐hospital death rate, which has been previously described as the ‘obesity mortality paradox’ in patients with HF 42–44 . Interestingly, COVID‐19 case volume was inversely associated with in‐hospital death.…”

Section: Discussionmentioning

confidence: 81%

“…41 Obesity was associated with a reduced in-hospital death rate, which has been previously described as the 'obesity mortality paradox' in patients with HF. [42][43][44] Interestingly, COVID-19 case volume was inversely associated with in-hospital death. There is no obvious explanation and none of the aforementioned studies examined a comparable variable with regard to in-hospital outcome.…”

Section: Discussionmentioning

confidence: 99%

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In‐hospital care in acute heart failure during the COVID‐19 pandemic: insights from the German‐wide Helios hospital network

König

Hohenstein

Meier‐Hellmann

et al. 2020

European J of Heart Fail

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Aims The coronavirus disease 2019 (COVID‐19) pandemic has led to changes in health care utilization for different acute cardiovascular diseases. Whether hospitalization rates and in‐hospital mortality were affected by the pandemic in patients with acute symptomatic heart failure (HF) was investigated in this study. Methods and results Administrative data provided by 67 German Helios hospitals were examined for patients with a main discharge diagnosis of HF using ICD codes. Urgent hospital admissions per day were compared for a study period (13 March–21 May 2020) with control intervals in 2020 (1 January–12 March) and 2019 (13 March–21 May), resulting in a total of 13 484 patients excluding all patients with laboratory‐proven COVID‐19 infection. Incidence rate ratios (IRR) were calculated using Poisson regression. Generalized linear mixed models were used for univariable and multivariable analysis to identify predictors of in‐hospital mortality. The number of admissions per day was lower in the study period compared to the same year [IRR 0.69, 95% confidence interval (CI) 0.67–0.73, P < 0.01] and the previous year control group (IRR 0.73, 95% CI 0.70–0.76, P < 0.01). Age was similar throughout the intervals, but case severity increased in terms of distribution within New York Heart Association (NYHA) classes and comorbidities. Within the study period, 30‐day rates for urgent hospital readmissions were higher compared to the same year but not the previous year control group. In‐hospital mortality was 7.3% in the study period, 6.1% in the same year (P = 0.03) and 6.0% in the previous year control group (P = 0.02). In multivariable analysis, age, NYHA class and other predictors of fatal outcome were identified but hospitalization during the study period was not independently associated with mortality. Conclusion Our data showed a significant reduction of urgent hospital admissions for HF with increased case severity and concomitant in‐hospital mortality during the COVID‐19 pandemic in Germany. Identifying causes of reduced inpatient treatment rates is essential for the understanding and valuation with regard to future optimal management of patients with HF.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

In‐hospital care in acute heart failure during the COVID‐19 pandemic: insights from the German‐wide Helios hospital network

König

Hohenstein

Meier‐Hellmann

et al. 2020

European J of Heart Fail

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“…The prevalence of obesity was higher in the ‘apparent resistant hypertension’ group, compared with both the ‘non-resistant’ hypertension and controlled blood pressure groups (who had a similar prevalence of obesity) and more obese HFpEF patients have higher heart failure hospitalization rates. 37 Baseline use of an MRA was lowest in patients with apparent resistant hypertension and highest in those with a controlled blood pressure group, and MRA therapy may reduce the risk of heart failure hospitalization in HFpEF. 23 Conversely, the use of alpha-adrenoceptor antagonists was much higher among patients with apparent resistant hypertension than in the other groups, and alpha-blockers increase the risk of heart failure hospitalization in patients with hypertension.…”

Section: Discussionmentioning

confidence: 94%

Sacubitril–valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction

Jackson

Jhund

Anand

et al. 2021

European Heart Journal

107

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Aims Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on ‘apparent resistant hypertension’ in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril–valsartan with valsartan. Methods and results In this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n = 4795). ‘Apparent resistant hypertension’ was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite treatment with valsartan, a calcium channel blocker, and a diuretic. ‘Apparent mineralocorticoid receptor antagonist (MRA)-resistant’ hypertension was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite the above treatments and an MRA. The primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes. We examined clinical endpoints and the safety of sacubitril–valsartan according to the hypertension category. We also examined reductions in blood pressure from the end of valsartan run-in to Weeks 4 and 16 after randomization. Overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension. The rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6–19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7–14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05–1.57). The reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril–valsartan vs. valsartan in patients with apparent resistant hypertension [−4.8 (−7.0 to −2.5) and 3.9 (−6.6 to −1.3) mmHg] and apparent MRA-resistant hypertension [−8.8 (−14.0 to −3.5) and −6.3 (−12.5 to −0.1) mmHg]. The proportion of patients with apparent resistant hypertension achieving a controlled systolic blood pressure by Week 16 was 47.9% in the sacubitril–valsartan group and 34.3% in the valsartan group [adjusted odds ratio (OR) 1.78, 95% CI 1.30–2.43]. In patients with apparent MRA-resistant hypertension, the respective proportions were 43.6% vs. 28.4% (adjusted OR 2.63, 95% CI 1.18–5.89). Conclusion Sacubitril–valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA. Clinical trial registration PARAGON-HF: ClinicalTrials.gov Identifier NCT01920711.

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“… 29 Shah et al 30 evaluated 6142 patients with acute HF across four continents and found that for every 5-unit increase in BMI, there was an 11% decrease in 30-day mortality and a 9% decrease at 1 year. Mandviwala et al 31 studied 2501 ambulatory HFpEF patients in 153 Veterans Affairs medical centers over 2 years and found that overweight and obese patients had improved survival compared to normal BMI, however time to HF hospitalization was shorter with increasing BMI. This study showed that increasing BMI was independently associated with an increased risk of HF hospitalization and similar risk for all-cause hospitalization, despite demonstrating an obesity paradox for survival.…”

Section: Obesity Paradox In Hfmentioning

confidence: 99%

Implications of obesity across the heart failure continuum

Elagizi

Carbone

Lavie

et al. 2020

Progress in Cardiovascular Diseases

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The obesity paradox, which suggests a survival advantage for the obese in heart failure (HF) has sparked debate in the medical community. Studies demonstrate a survival advantage in obese patients with HF, including those with advanced HF requiring continuous inotropic support for palliation or disease modifying therapy with a left ventricular assist device (LVAD) or heart transplantation (HT). Importantly, the obesity paradox is affected by the level of cardiorespiratory fitness (CRF). It is now recommended that HF patients with body mass index ≥35 kg/m 2 achieve at least 5–10% weight loss, in order to improve symptoms and cardiac function, though more robust data are urgently needed. CRF may be the single best predictor of overall health and small improvements in fitness levels may lead to improved outcomes in HF. In addition to implications of obesity in chronic HF, we also discuss management of obese patients with advanced HF and their implications for therapies such as LVAD implantation and HT.

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Obesity and the paradox of mortality and heart failure hospitalization in heart failure with preserved ejection fraction

Cited by 32 publications

References 35 publications

In‐hospital care in acute heart failure during the COVID‐19 pandemic: insights from the German‐wide Helios hospital network

In‐hospital care in acute heart failure during the COVID‐19 pandemic: insights from the German‐wide Helios hospital network

Sacubitril–valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction

Implications of obesity across the heart failure continuum

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