Diabetes as a risk factor for heart failure in women and men: a systematic review and meta-analysis of 47 cohorts including 12 million individuals

Ohkuma, Toshiaki; Komorita, Yuji; Peters, Sanne A.E.; Woodward, Mark

doi:10.1007/s00125-019-4926-x

Cited by 185 publications

(130 citation statements)

References 47 publications

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“…We found a slight male disadvantage in the association between diabetes and PAD in the results Fig. 4 Multiple-adjusted ratio of women: men relative risks (RRRs) for incident coronary heart disease [8], stroke [9], vascular dementia [10], heart failure [11], and PAD, comparing individuals with diabetes to those without diabetes aggregated across cross-sectional studies, though this finding was not consistent across all included studies. The disadvantage in men may be a spurious finding resulting from the "chicken and egg" problem inherent to cross-sectional design; in addition to diabetes increasing risk for PAD, PAD is known to be a modest but independent risk factor for diabetes [42].…”

Section: Strengths and Limitationsmentioning

confidence: 85%

“…Research by this team and others has provided strong evidence that, while women have lower risk for CVD overall, diabetes confers an excess relative risk in women for the onset of CVDs, including coronary heart disease, stroke, heart failure, and vascular dementia [8][9][10][11][12][13][14][15] that partially erases this female "biological advantage [16]. " The reasons for this advantage in women without diabetes compared to men of the same age are not entirely clear, but likely the result of multifactorial contributions including the protective effect of estrogen/harmful effect of testosterone, differences in cardiovascular risk factors, and sex differences in the diagnosis and treatment of diabetes and cardiovascular disease [17].…”

Section: Introductionmentioning

confidence: 99%

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Diabetes as a risk factor for incident peripheral arterial disease in women compared to men: a systematic review and meta-analysis

Chase-Vilchez

Chan

Peters

et al. 2020

Cardiovasc Diabetol

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Aims/hypothesis Previous meta-analyses have suggested that diabetes confers a greater excess risk of coronary heart disease, stroke, vascular dementia, and heart failure in women compared to men. While the underlying mechanism that explains such greater excess risk is unknown, in the current meta-analysis we hypothesized that we would find a similar sex difference in the relationship between diabetes and peripheral arterial disease (PAD). Methods PubMed MEDLINE, the Cochrane Database of Systematic Reviews, and Embase were systematically searched for prospective population-based cohort studies, with no restriction on publication date, language, or country. We included studies that reported the relative risk (RR), and its variability, for incident PAD associated with diabetes in both sexes. We excluded studies that did not adjust at least for age, and in which participants had pre-existing PAD. In cases where sex-specific results were not reported, study authors were contacted. Random-effects meta-analyses with inverse variance weighting were used to obtain summary sex-specific RRs and the women: men ratio of RRs for PAD. The Newcastle–Ottawa scale was used to assess study quality. Results Data from seven cohorts, totalling 2071,260 participants (49.8% women), were included. The relative risk for incident PAD associated with diabetes compared with no diabetes was 1.96 (95% CI 1.29–2.63) in women and 1.84 (95% CI 1.29–2.86) in men, after adjusting for potential confounders. The multiple-adjusted RR ratio was 1.05 (95% CI 0.90–1.22), with virtually no heterogeneity between studies (I2 = 0%). All studies scored 6–8, on the Newcastle–Ottawa scale of 0–9, indicating good quality. Eleven of the 12 studies that met review inclusion criteria did not report sex-specific relative risk, and these data were collected through direct correspondence with the study authors. Conclusion/interpretation Consistent with other studies, we found evidence that diabetes is an independent risk factor for PAD. However, in contrast to similar studies of other types of cardiovascular disease, we did not find evidence that diabetes confers a greater excess risk in women compared to men for PAD. More research is needed to explain this sex differential between PAD and other forms of CVD, in the sequelae of diabetes. In addition, we found that very few studies reported the sex-specific relative risk for the association between diabetes and PAD, adding to existing evidence for the need for improved reporting of sex-disaggregated results in cardiovascular disease research.

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Section: Strengths and Limitationsmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Diabetes as a risk factor for incident peripheral arterial disease in women compared to men: a systematic review and meta-analysis

Chase-Vilchez

Chan

Peters

et al. 2020

Cardiovasc Diabetol

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“…Differences exist in cardiovascular disease biology between women and men. For example, women experience HF with preserved ejection fraction more frequently as a result of hypertension and/or diabetes, while HF with reduced ejection fraction from prior ischemic events is more frequent in men ( 25-29 ). Thus, sex-specific consideration of cardiovascular responses to abaloparatide were not encompassed by this study.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Safety of Abaloparatide in Postmenopausal Women With Osteoporosis: Analysis From the ACTIVE Phase 3 Trial

Cosman

Peterson

Towler

et al. 2020

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Abaloparatide is an FDA-approved PTHrp analog for treatment of osteoporosis in postmenopausal women at high risk of fracture. Objectives We assessed the cardiovascular safety profile of abaloparatide. Design Review of heart rate (HR), blood pressure (BP), and cardiovascular-related adverse events (AEs), including major adverse cardiovascular events (MACE) and heart failure (HF) from: (a) ACTIVE (NCT01343004), a phase 3 trial that randomized 2463 postmenopausal women with osteoporosis to abaloparatide, teriparatide, or placebo for 18 months; (b) ACTIVExtend (NCT01657162), where participants from the abaloparatide and placebo arms received alendronate for 2 years; and (c) a pharmacology study in 55 healthy adults. Results Abaloparatide and teriparatide transiently increased HR relative to placebo. Following first dose, mean (SD) HR change from pre-treatment to 1 hour post treatment was 7.9 (8.5) bpm for abaloparatide, 5.3 (7.5) for teriparatide, and 1.2 (7.1) for placebo. A similar pattern was observed over subsequent visits. In healthy volunteers, HR increase resolved within 4 hours. The corresponding change in mean supine systolic and diastolic BP 1 hour post treatment was -2.7/-3.6 mmHg (abaloparatide), -2.0/-3.6 (teriparatide), and -1.5/-2.3 (placebo). The percentage of participants with serious cardiac AEs was similar among groups (0.9‒1.0%). In a post hoc analysis, time-to-first incidence of MACE + HF was longer with abaloparatide (P = 0.02 versus placebo) and teriparatide (P = 0.04 versus placebo). Conclusions Abaloparatide was associated with transient increases in HR and small decreases in BP in postmenopausal women with osteoporosis, with no increase in risk of serious cardiac AEs, MACE, or HF.

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“…This sex discrepancy, which remains still incompletely understood, was first observed in the Framingham Heart Study, where diabetic men presented with a 2-fold, while diabetic women presented with a 4-fold increased risk of HF after adjustment for age and other CV risk factors [23]. The same finding was further confirmed in a comprehensive systematic review and meta-analysis of 47 cohorts including more than 12 million Japanese diabetic patients, which demonstrated that both type 1 diabetes mellitus (T1DM) and T2DM are stronger risk factors for HF in women than in men [24]. Potential explanations for this gender-specific effect in the epidemiology of DM-associated HF include the higher prevalence of DCM in women, the stronger correlation of DM with CHD in women, the longer exposure of women to hyperglycemia in the prediabetic state, sex-specific differences in other CV risk factors, and finally the fact that diabetic men are more prone to premature death and thus will not survive to develop HF (survival bias) [25][26][27][28].…”

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confidence: 73%

Important Considerations for the Treatment of Patients with Diabetes Mellitus and Heart Failure from a Diabetologist’s Perspective: Lessons Learned from Cardiovascular Outcome Trials

Koliaki

Katsilambros

2019

IJERPH

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Heart failure (HF) represents an important cardiovascular complication of type 2 diabetes mellitus (T2DM) associated with substantial morbidity and mortality, and is emphasized in recent cardiovascular outcome trials (CVOTs) as a critical outcome for patients with T2DM. Treatment of T2DM in patients with HF can be challenging, considering that these patients are usually elderly, frail and have extensive comorbidities, most importantly chronic kidney disease. The complexity of medical regimens, the high risk clinical characteristics of patients and the potential of HF therapies to interfere with glucose metabolism, and conversely the emerging potential of some antidiabetic agents to modulate HF outcomes, are only some of the challenges that need to be addressed in the framework of a team-based personalized approach. The presence of established HF or the high risk of developing HF in the future has influenced recent guideline recommendations and can guide therapeutic decision making. Metformin remains first-line treatment for overweight T2DM patients at moderate cardiovascular risk. Although not contraindicated, metformin is no longer considered as first-line therapy for patients with established HF or at risk for HF, since there is robust scientific evidence that treatment with other glucose-lowering agents such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) should be prioritized in this population due to their strong and remarkably consistent beneficial effects on HF outcomes.

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Diabetes as a risk factor for heart failure in women and men: a systematic review and meta-analysis of 47 cohorts including 12 million individuals

Cited by 185 publications

References 47 publications

Diabetes as a risk factor for incident peripheral arterial disease in women compared to men: a systematic review and meta-analysis

Diabetes as a risk factor for incident peripheral arterial disease in women compared to men: a systematic review and meta-analysis

Cardiovascular Safety of Abaloparatide in Postmenopausal Women With Osteoporosis: Analysis From the ACTIVE Phase 3 Trial

Important Considerations for the Treatment of Patients with Diabetes Mellitus and Heart Failure from a Diabetologist’s Perspective: Lessons Learned from Cardiovascular Outcome Trials

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