Impact of Sex Differences and Diabetes on Coronary Atherosclerosis and Ischemic Heart Disease

Madonna, Rosalinda; Balistreri, Carmela Rita; Rosa, Salvatore De; Muscoli, Saverio; Selvaggio, Stefano; Selvaggio, Giancarlo; Ferdinándy, Péter; Caterina, Raffaele De

doi:10.3390/jcm8010098

Cited by 65 publications

(47 citation statements)

References 115 publications

(142 reference statements)

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“…Given that the underlying mechanism by which diabetes might confer this greater excess risk to women for other incident cardiovascular diseases is still unknown [38], it is challenging to explain why we do not see a sexspecific effect for the relationship between diabetes and PAD, which is also a type of cardiovascular disease. However, one possible explanation lies in the finding that the more pronounced increase in relative risk for CVD events in women with diabetes compared to men appears, in part, to reflect the lower disease risk in women compared with men without diabetes [16].…”

Section: Sex Differences In Other Cvdsmentioning

confidence: 88%

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: Sex Differences In Other Cvdsmentioning

confidence: 88%

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

View full text Add to dashboard Cite

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“…The increase in AGE levels, secondary to hyperglycemia, increases the receptor for AGE (RAGE), resulting in increased ROS production and leading to activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling with the production of inflammatory cytokines [20]. Excessive AGE formation leads to the loss of pericytes, increased platelet aggregation, and endothelial dysfunction, all abnormalities that can promote pro-coagulant status with consequent ischemia damage [21].…”

Section: Figurementioning

confidence: 99%

Diabetic Cardiomyopathy and Ischemic Heart Disease: Prevention and Therapy by Exercise and Conditioning

Crisafulli

Pagliaro

Roberto

et al. 2020

IJMS

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Metabolic syndrome, diabetes, and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. In addition, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.

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“…Hypertension, diabetes, sex differences, obesity, smoking and high cholesterol are the most important risk factors for cardiovascular diseases (2,3). Recent studies have demonstrated that the abnormal accumulation of plasma homocysteine (Hcy) is a risk factor for cardiovascular diseases, which may lead to myocardial cell dysfunction by inducing apoptosis (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Pirfenidone attenuates homocysteine‑induced apoptosis by regulating the connexin 43 pathway in H9C2 cells

Chen

Ouyang

et al. 2020

Int J Mol Med

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Pirfenidone (PFd) is an anti-fibrotic agent that is clinically used in the treatment of idiopathic pulmonary fibrosis. PFd has been shown to exert protective effects against damage to orbital fibroblasts, endothelial cells, liver cells and renal proximal tubular cells; however, its effect on myocardial cell apoptosis remains unclear. The present study aimed to characterize the effects of PFd on homocysteine (Hcy)-induced cardiomyocyte apoptosis and investigated the underlying mechanisms. H9c2 rat cardiomyocytes were pre-treated with PFd for 30 min followed by Hcy exposure for 24 h. The effects of PFd on cell cytotoxicity were evaluated by ccK-8 assay. The apoptosis rate of each group was determined by flow cytometry. The protein and mRNA levels of connexin 43 (cx43), Bax, B-cell lymphoma-2 (Bcl-2) and caspase-3 were measured by western blot analysis and reverse transcription-quantitative PcR, respectively. The present results demonstrated that the apoptotic rate increased following Hcy exposure, whereas the apoptotic rate significantly decreased following PFd pre-treatment. Furthermore, the ratio of Bax/Bcl2 was upregulated following Hcy exposure, and Hcy upregulated the expression levels of cleaved caspase-3 and cx43. Notably, these effects were prevented by PFd. Additionally, the effects of PFd were inhibited by the Cx43 agonist, AAP10. In summary, the findings of the present study demonstrate that PFd protects H9c2 rat cardiomyocytes against Hcy-induced apoptosis by modulating the cx43 signaling pathway.

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Impact of Sex Differences and Diabetes on Coronary Atherosclerosis and Ischemic Heart Disease

Cited by 65 publications

References 115 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

Diabetic Cardiomyopathy and Ischemic Heart Disease: Prevention and Therapy by Exercise and Conditioning

Pirfenidone attenuates homocysteine‑induced apoptosis by regulating the connexin 43 pathway in H9C2 cells

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