Insulin Resistance and Risk of Congestive Heart Failure

Ingelsson, Erik; Sundström, Johan; Ärnlöv, Johan; Zethelius, Björn; Lind, Lars

doi:10.1001/jama.294.3.334

Cited by 516 publications

(321 citation statements)

References 37 publications

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“…Adiposity is associated with increased risk of hypertension, 2 insulin resistance, 54 diabetes mellitus, 55 and dyslipidemia, 56 all of which increase the risk of myocardial infarction 57 and may thereby increase the risk of heart failure. 9,34,58 However, the exploratory analysis with and without adjustment for incident myocardial infarction suggested only small differences with such an adjustment, suggesting that a relatively small proportion of heart failure cases might be explained by this mechanistic pathway. Hypertension and diabetes mellitus also strongly increase the risk of heart failure independently of other risk factors.…”

Section: Discussionmentioning

confidence: 99%

Body Mass Index, Abdominal Fatness, and Heart Failure Incidence and Mortality

et al. 2016

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T he prevalence of overweight and obesity has increased rapidly over the last decades in all areas of the world. 1 This has raised serious public health concerns owing to the association between overweight and obesity and the increased risk of a wide range of chronic diseases, including cardiovascular diseases, type 2 diabetes mellitus, total mortality, and several types of cancer. 2-4 Clinical Perspective on p 649Heart failure is a major public concern. Heart failure affected ≈5 million Americans in 2005, and economic costs are estimated at US $27.9 billion.5 Mortality in heart failure remains high, ranging from 20% to 40% despite advances in the management of heart failure. 6,7 Several prospective studies have reported increased risk of heart failure with a greater body mass index (BMI), and although most studies report an increased risk of heart failure in the obese range (BMI ≥30 kg/m 2 ), it is less clear whether overweight (BMI, kg/ m 2 ) increases the risk; some studies found a significant association, 10,16,17,20,25,31,32 whereas others did not. 8,12,19,21,23,[27][28][29][30]33,34 A pooled analysis of 32 cohort studies in Asia and the Pacific found an increased risk of heart failure mortality among obese individuals, but there was no association among overweight subjects. 35 However, it is possible that the association between BMI and heart failure differs for incidence and mortality because mortality depends on both the incidence and prognosis after heart failure is established and because there is indication of an obesity paradox observed in heart failure patients, with improved survival among overweight and obese persons with established heart failure. 36 This uncertainty is also reflected in the Heart Failure Society of America practice guidelines in which the goal for management of BMI is set at a BMI <30 kg/m 2 . 37 However, this may be a suboptimal goal if risk of heart failure incidence also increases in overweight subjects.Background-Obesity has been associated with increased risk of heart failure, but whether overweight also increases risk is unclear. It is also unclear whether abdominal adiposity is more strongly associated with heart failure risk than general adiposity. We conducted a systematic review and meta-analysis of prospective studies to clarify the strength and shape of the dose-response relationship between general and abdominal adiposity and the risk of heart failure. Methods and Results-PubMed and Embase databases were searched up to October 10, 2014. Summary relative risks were calculated using random-effects models. A total of 28 studies (27 publications) were included. Twenty-three prospective studies with >15 905 incident cases among 647 388 participants were included in the analysis of body mass index and heart failure incidence, and 4 studies were included for heart failure mortality. The summary relative risk for a 5-unit increment in body mass index was 1.41 (95% confidence interval, 1.34-1.47; I 2 =83%) for heart failure incidence and 1.26 (95% confidence interval, 0....

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Section: Discussionmentioning

confidence: 99%

Body Mass Index, Abdominal Fatness, and Heart Failure Incidence and Mortality

et al. 2016

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“…In the Uppsala study, insulin sensitivity, but not anthropometric indexes of obesity, was independently predictive of HF risk. 99 In a cohort study from Greece, individuals with normal BMI and metabolic syndrome were at substantially higher risk of HF at 6 years compared with obese individuals without metabolic syndrome. 198 Analyses from MESA (Multi-Ethnic Study of Atherosclerosis) suggest that inflammation may potentiate the link between obesity and the risk of developing HF.…”

Section: Other Medicationsmentioning

confidence: 99%

“…18,19 Studies have also demonstrated that milder elevations in glucose and abnormalities in insulin resistance, even in the absence of overt diabetes mellitus, are associated with an increased risk for HF. 99,100 In individuals without known diabetes mellitus or HF at baseline in the ARIC study (Atherosclerosis Risk in Communities), the risk of incident HF was higher in individuals with hemoglobin A1c (HbA1c) of 6.0% to 6.4% (HR,1.40; 95% CI, 1.09-1.79) and HbA1c of 5.5% to 6.0% (HR,1.16; 95% CI, 0.98-1.37) compared with those with an HbA1c of 5.0% to 5.4% 100 ( Table 5). The mechanisms contributing to the greater degree of HF in individuals with diabetes mellitus are likely multifactorial and include the commonly shared HF risk factors of hypertension, coronary artery disease, renal 104 Between 1995 and 1999 in Olmsted County, Minnesota, the prevalence of diabetes mellitus in patients with incident HF was 25%.…”

Section: Association Of Diabetes Mellitus With the Development Of Incmentioning

confidence: 99%

Contributory Risk and Management of Comorbidities of Hypertension, Obesity, Diabetes Mellitus, Hyperlipidemia, and Metabolic Syndrome in Chronic Heart Failure: A Scientific Statement From the American Heart Association

Bozkurt¹,

Aguilar²,

Deswal³

et al. 2016

Circulation

366

220

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CLINICAL STATEMENTS AND GUIDELINESfailed to show a significant reduction of SBP in patients with resistant hypertension. 81 Other strategies such as targeting excessive sympathetic nerve activity by carotid body denervation are awaiting clinical validation in the hypertension and HF populations. Drugs to Avoid in Patients With HFSeveral classes of drugs should be avoided in patients with HFrEF with a history of hypertension. Because of their negative inotropic properties and the increased likelihood of worsening HF symptoms, the nondihydropyridine calcium channel blockers such as diltiazem and verapamil should be avoided. 8 The dihydropyridine calcium channel blocker amlodipine appeared to be safe in patients with severe HFrEF in the PRAISE trial (Prospective Randomized Amlodipine Survival Evaluation), 82 as was felodipine. 73 In the current 2013 HF guidelines, most calcium channelblocking drugs except amlodipine are not recommended. 8Although clonidine is an effective antihypertensive agent, a similar centrally acting drug, moxonidine, was associated with increased mortality in patients with HF; thus, centrally acting norepinephrine-depleting agents may need to be avoided or used with caution in patients with HFrEF. 83In the ALLHAT trial, the α-blocker doxazosin arm of the trial was discontinued because of a 2-fold increase in the risk of developing HF compared with chlorthalidone treatment. 45 Although the ALLHAT study excluded patients with established HF and there are caveats about extrapolating these data to the management of hypertension in patients with established HF, the safety and efficacy of α-blockers in the management of patients with HF with hypertension are currently unclear. Potent direct-acting vasodilators such as minoxidil should also be avoided because of their renin-related salt and fluid-retaining effects. Nonsteroidal anti-inflammatory agents should be used with caution in these patients, given their effects on BP, volume status, and renal function. Treatment of Hypertension in Patients With HF With Preserved LVEFMost patients with HF and preserved LVEF (HFpEF), especially elderly women, have hypertension. A significant proportion of these patients also have evidence of LV hypertrophy, and some may have atrial dilatation, cardiac enlargement, and wall motion abnormalities without LV systolic dysfunction. Patients with HFpEF may respond particularly well to the treatment of hypertension with regression of hypertrophy 84 and improvement in filling pressures. 84,85 Most patients with HFpEF require treatment with cardiac medications for the comorbidities of hypertension, diabetes mellitus, coronary artery disease, and atrial fibrillation. The 2013 HF guidelines suggest that the use of β-blocking agents, ACE inhibitors, and ARBs in patients with hypertension is reasonable to control BP in patients with HFpEF. 8 The use of ARBs might also be considered to decrease hospitalizations for patients with HFpEF. recommendations Harmonized With Existing Guidelines for the recognition and Treatment of pa...

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“…Similar data were obtained from a Finnish study, showing a greater risk of HF in overweight and obese subjects than that in normal-weight participants . However, while some authors attribute these correlations to the downstream development of metabolic risk factors such as inflammation, insulin resistance or type 2 diabetes mellitus (Ingelsson et al 2005, Bahrami et al 2008, Voulgari et al 2011, the data from other studies report that obesity directly correlates with the risk of HF, independent of other metabolic risk factors (Morkedal et al 2014). Paradoxically, once HF has been established, obesity confers survival benefits (Oreopoulos et al 2008, Shah et al 2014.…”

Section: Obesity As a Risk Factor For Heart Failurementioning

confidence: 99%

Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease

Rodríguez-Calvo¹,

Girona²,

Alegret

et al. 2017

Journal of Endocrinology

100

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Obesity and ectopic fat accumulation in non-adipose tissues are major contributors to heart failure (HF) and cardiovascular disease (CVD). Adipocytes act as endocrine organs by releasing a large number of bioactive molecules into the bloodstream, which participate in a communication network between white adipose tissue and other organs, including the heart. Among these molecules, fatty acid-binding protein 4 (FABP4) has recently been shown to increase cardiometabolic risk. Both clinical and experimental evidence have identified FABP4 as a relevant player in atherosclerosis and coronary artery disease, and it has been directly related to cardiac alterations such as left ventricular hypertrophy (LVH) and both systolic and diastolic cardiac dysfunction. The available interventional studies preclude the establishment of a direct causal role of this molecule in CVD and HF and propose FABP4 as a biomarker rather than as an aetiological factor. However, several experimental reports have suggested that FABP4 may act as a direct contributor to cardiac metabolism and physiopathology, and the pharmacological targeting of FABP4 may restore some of the metabolic alterations that are conducive to CVD and HF. Here, we review the current knowledge regarding FABP4 in the context of HF and CVD as well as the molecular basis by which this protein participates in the regulation of cardiac function.

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Insulin Resistance and Risk of Congestive Heart Failure

Abstract: Insulin resistance predicted CHF incidence independently of established risk factors including diabetes in our large community-based sample of elderly men. The previously described association between obesity and subsequent CHF may be mediated largely by insulin resistance.

Cited by 516 publications

References 37 publications

Body Mass Index, Abdominal Fatness, and Heart Failure Incidence and Mortality

Body Mass Index, Abdominal Fatness, and Heart Failure Incidence and Mortality

Contributory Risk and Management of Comorbidities of Hypertension, Obesity, Diabetes Mellitus, Hyperlipidemia, and Metabolic Syndrome in Chronic Heart Failure: A Scientific Statement From the American Heart Association

Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease

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