Sex Differences in the Excess Risk of Cardiovascular Diseases Associated with Type 2 Diabetes: Potential Explanations and Clinical Implications

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Abstract

Strong evidence suggests that type 2 diabetes confers a stronger excess risk of cardiovascular diseases in women than in men; with women having a 27 % higher relative risk of stroke and a 44 % higher relative risk of coronary heart disease compared with men. The mechanisms that underpin these sex differences in the associations between diabetes and cardiovascular disease risk are not fully understood. Some of the excess risk may be the result of a sex disparity in the management and treatment of diabetes, to the detriment of women. However, accruing evidence suggests that real biological differences between men and women underpin the excess risk of diabetes-related cardiovascular risk in women such that there is a greater decline in risk factor status in women than in men in the transition from normoglycemia to overt diabetes. This greater risk factor decline appears to be associated with women having to put on more weight than men, and thus attain a higher body mass index, to develop diabetes. Further studies addressing the mechanisms responsible for sex differences in the excess risk of cardiovascular diseases associated with diabetes are needed to improve the prevention and management of diabetes in clinical practise.

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Most cited references 23

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Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes.

N. Morrish, S.-L. Wang, L Stevens … (2001)

We aimed to examine the mortality rates, excess mortality and causes of death in diabetic patients from ten centres throughout the world. A mortality follow-up of 4713 WHO Multinational Study of Vascular Disease in Diabetes (WHO MSVDD) participants from ten centres was carried out, causes of death were ascertained and age-adjusted mortality rates were calculated by centre, sex and type of diabetes. Excess mortality, compared with the background population, was assessed in terms of standardised mortality ratios (SMRs) for each of the 10 cohorts. Cardiovascular disease was the most common underlying cause of death, accounting for 44 % of deaths in Type I (insulin-dependent) diabetes mellitus and 52 % of deaths in Type II (non-insulin-dependent) diabetes mellitus. Renal disease accounted for 21% of deaths in Type I diabetes and 11% in Type II diabetes. For Type I diabetes, all-cause mortality rates were highest in Berlin men and Warsaw women, and lowest in London men and Zagreb women. For Type II diabetes, rates were highest in Warsaw men and Oklahoma women and lowest in Tokyo men and women. Age adjusted mortality rates and SMRs were generally higher in patients with Type I diabetes compared with those with Type II diabetes. Men and women in the Tokyo cohort had a very low excess mortality when compared with the background population. This study confirms the importance of cardiovascular disease as the major cause of death in people with both types of diabetes. The low excess mortality in the Japanese cohort could have implications for the possible reduction of the burden of mortality associated with diabetes in other parts of the world.

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Sex differences in lifetime risk and first manifestation of cardiovascular disease: prospective population based cohort study

Maarten J. G. Leening, Bart Ferket, Ewout W. Steyerberg … (2014)

Objective To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework. Design Prospective population based cohort study. Setting People living in the community in Rotterdam, the Netherlands. Participants 8419 participants (60.9% women) aged ≥55 and free from cardiovascular disease at baseline. Main outcome measures First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death. Results During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetime risks of cardiovascular disease were 67.1% (95% confidence interval 64.7% to 69.5%) for men and 66.4% (64.2% to 68.7%) for women. Lifetime risks of first incident manifestations of cardiovascular disease in men were 27.2% (24.1% to 30.3%) for coronary heart disease, 22.8% (20.4% to 25.1%) for cerebrovascular disease, 14.9% (13.3% to 16.6%) for heart failure, and 2.3% (1.6% to 2.9%) for other deaths from cardiovascular disease. For women the figures were 16.9% (13.5% to 20.4%), 29.8% (27.7% to 31.9%), 17.5% (15.9% to 19.2%), and 2.1% (1.6% to 2.7%), respectively. Differences in the number of events that developed over the lifespan in women compared with men (per 1000) were −7 for any cardiovascular disease, −102 for coronary heart disease, 70 for cerebrovascular disease, 26 for heart failure, and −1 for other cardiovascular death; all outcomes manifested at a higher age in women. Patterns were similar when analyses were restricted to hard atherosclerotic cardiovascular disease outcomes, but absolute risk differences between men and women were attenuated for both coronary heart disease and stroke. Conclusions At age 55, though men and women have similar lifetime risks of cardiovascular disease, there are considerable differences in the first manifestation. Men are more likely to develop coronary heart disease as a first event, while women are more likely to have cerebrovascular disease or heart failure as their first event, although these manifestations appear most often at older ages.

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Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women's Heart Health Study.

P Whincup, D Lawlor, N Sattar … (2011)

Type 2 diabetes is associated with greater relative risk of CHD in women than in men, which is not fully explained by conventional cardiovascular risk factors. We assessed whether cardiovascular risk factors including more novel factors such as markers of insulin resistance, inflammation, activated coagulation and endothelial dysfunction differ more between diabetic and non-diabetic women than between diabetic and non-diabetic men, and the role of insulin resistance. A cross-sectional study of non-diabetic and diabetic men and women (n = 7,529) aged 60-79 years with no previous myocardial infarction who underwent an examination was conducted. Measurements of anthropometry, blood pressure and fasting measurements of lipids, insulin, glucose and haemostatic and inflammatory markers were taken. Non-diabetic women tended to have more favourable risk factors and were less insulin resistant than non-diabetic men, but this was diminished in the diabetic state. Levels of waist circumference, BMI, von Willebrand factor (VWF), WBC count, insulin resistance (HOMA-IR), diastolic blood pressure, HDL-cholesterol, tissue plasminogen activator (t-PA) and factor VIII differed more between diabetic and non-diabetic women than between diabetic and non-diabetic men (test for diabetes × sex interaction p < 0.05). The more adverse effect of diabetes on these risk markers in women was associated with, and thereby largely attenuated by, insulin resistance. The greater adverse influence of diabetes per se on adiposity and HOMA-IR and downstream blood pressure, lipids, endothelial dysfunction and systemic inflammation in women compared with men may contribute to their greater relative risk of coronary heart disease.

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Author and article information

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Sanne A. E. Peters: +44 1865 617 200 , peters@georgeinstitute.ox.ac.uk

Journal

Journal ID (nlm-ta): Curr Cardiovasc Risk Rep

Journal ID (iso-abbrev): Curr Cardiovasc Risk Rep

Title: Current Cardiovascular Risk Reports

Publisher: Springer US (New York )

ISSN (Print): 1932-9520

ISSN (Electronic): 1932-9563

Publication date (Electronic): 26 May 2015

Publication date PMC-release: 26 May 2015

Publication date (Print): 2015

Volume: 9

Issue: 7

Electronic Location Identifier: 36

Affiliations

[ ]The George Institute for Global Health, Nuffield Department of Population Health, University of Oxford, 34 Broad Street, Oxford, OX1 3BD UK

[ ]School of Public Health, University of Queensland, Brisbane, Australia

[ ]Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK

[ ]The George Institute for Global Health, University of Sydney, Sydney, Australia

[ ]Department of Epidemiology, Johns Hopkins University, Baltimore, MD USA

Article

Publisher ID: 462

DOI: 10.1007/s12170-015-0462-5

PMC ID: 4442131

PubMed ID: 26029318

SO-VID: 552f4bcd-b599-44f6-8400-f1fd7885906e

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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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ScienceOpen disciplines: Cardiovascular Medicine

Keywords: diabetes,cardiovascular disease,coronary heart disease,stroke,sex differences,men,women

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ScienceOpen disciplines: Cardiovascular Medicine

Keywords: diabetes, cardiovascular disease, coronary heart disease, stroke, sex differences, men, women

Sex Differences in the Excess Risk of Cardiovascular Diseases Associated with Type 2 Diabetes: Potential Explanations and Clinical Implications

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Most cited references 23

Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes.

Sex differences in lifetime risk and first manifestation of cardiovascular disease: prospective population based cohort study

Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women's Heart Health Study.

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