Elsevier

Diabetes & Metabolism

Volume 38, Issue 5, November 2012, Pages 420-427
Diabetes & Metabolism

Review
Mortality in diabetes compared with previous cardiovascular disease: A gender-specific meta-analysisComparaison du risque de mortalité chez les diabétiques et les patients non-diabétiques avec antécédent de malade cardiovasculaire : méta-analyse selon le sexe

https://doi.org/10.1016/j.diabet.2012.04.002Get rights and content

Abstract

Aims

Diabetes has been described as a cardiovascular disease (CVD) risk equivalent. There is evidence, however, that its impact may differ between women and men. For this reason, our study aimed to obtain gender-specific hazard ratios (HRs) comparing diabetes and CVD patients in terms of all-cause, CVD and coronary heart disease (CHD) mortality.

Methods

Individuals with diabetes (without CVD) and those with CVD (without diabetes) were examined through a systematic review of articles that provided gender-specific HRs for mortality. Searches included Medline, Embase and the Cochrane Library database (from January 1998 to December 2009) and exploded MeSH headings [cardiovascular diseases, risk, epidemiologic studies, case-control studies, cohort studies, mortality, outcome assessment (health care), sex factors, survival analysis and diabetes mellitus, type 2]. Two observers selected and reviewed the studies and hierarchical Bayesian random-effects models were used to combine HRs, thereby accommodating any between-study differences through inclusion of a between-study variance in HRs.

Results

Out of 5425 studies, nine were relevant (0.17%). CVD and CHD mortality in men was lower for diabetes alone (CVD mortality HR: 0.82, 95% CrI: 0.69–0.98; CHD mortality HR: 0.73, 95% CrI: 0.65–0.83). In contrast, rates appeared to be higher in women with diabetes alone (CVD mortality HR: 1.29, 95% CrI: 0.79–2.26; CHD mortality HR: 1.28, 95% CrI: 0.75–2.22), although wide credible intervals precluded any definitive conclusions. All-cause mortality in men was similar for diabetes and previous CVD (HR: 1.02, 95% CrI: 0.93–1.12) whereas, among women, it was at least as high and possibly higher for diabetes alone (HR: 1.25, 95% CrI: 0.89–1.76).

Conclusion

Compared with previous CVD, diabetes alone leads to lower CVD and CHD mortality risk in men, and similar all-cause mortality. In contrast, although further studies are needed, it is possible that diabetes leads to higher CVD, CHD and all-cause mortality in women.

Résumé

But

Le diabète (DM) a été considéré comme un facteur de risque de mortalité équivalent à celui d’un antécédent de maladie cardiovasculaire (MCV). Cependant, des données indiquent que son impact pourrait varier selon le sexe. Notre étude avait pour objet de comparer selon le sexe le risque de mortalité toutes causes confondues, de mortalité liée aux MCV et de mortalité liée aux maladies coronaires (MC) entre diabétiques et patients avec antécédent de MCV.

Méthodes

Nous avons inclus les données des personnes atteintes de DM (sans maladie cardiovasculaire) et des personnes avec antécédent de MCV (sans diabète) en procédant à un examen systématique des articles qui donnaient le risque de mortalité selon le sexe. Nous avons fait des recherches dans Medline, Embase et Cochrane sur la période janvier 1998 à décembre 2009, avec comme mots clés : maladies cardiovasculaires, risque, études épidémiologiques, études cas–témoin, études par cohortes, mortalité, évaluation des résultats (soins de santé), facteurs liés au sexe, analyse de survie, diabète sucré, type 2. Deux observateurs ont évalué la pertinence des études et revu celles-ci. Nous avons utilisé des modèles bayésiens hiérarchiques à effets aléatoires pour combiner les rapports de risques (RR) en vue de tenir compte des différences d’une étude à l’autre par l’inclusion d’un écart de résultats entre les études dans les RR.

Résultats

Neuf des 5425 études étaient pertinentes (0,17 %). La mortalité liée aux MCV et aux MC chez les hommes était plus faible chez les diabétiques sans antécédent de MCV (mortalité liée aux MCV : RR 0,82 ; IC 95 % 0,69–0,98 ; mortalité liée aux MC : RR 0,73 ; IC 95 % 0,65–0,83). En revanche le risque semblait plus élevé chez les femmes diabétiques (mortalité liée aux MCV : RR 1,29, IC 95 % 0,79–2,26 ; mortalité liée aux MC : RR 1,28, IC 95 % 0,75–2,22), mais l’importance des intervalles de confiance n’a pas permis de conclusion définitive. La mortalité toutes causes confondues chez les hommes était similaire pour le diabète et les antécédents de MCV (RR 1,02 ; IC 95 % 0,93–1,12). Chez les femmes, ces données étaient au moins aussi élevées, avec une tendance en faveur d’une élévation pour le diabète seul (RR 1,25, IC 95 % 0,89–1,76).

Conclusions

Chez les hommes, par comparaison aux non-diabétiques avec antécédent CV, les diabétiques sans antécédent CV ont un risque de mortalité liée aux MCV et aux MC plus faible et un risque de mortalité toutes causes confondues similaire. En revanche, il existe une tendance en faveur d’un risque plus élevé chez les femmes diabétiques de mortalité liée aux MCV, aux MC et toutes causes confondues que chez les femmes non-diabétiques avec antécédent de MCV. D’autres études sont cependant nécessaires pour affirmer ou infirmer ces données.

Introduction

Over 10 years ago, Haffner and colleagues [1] reported that mortality in diabetes patients was similar to that of patients with previous myocardial infarction (MI). These findings contributed to the concept of diabetes as a cardiovascular disease (CVD) ‘risk equivalent’ [2], [3], [4], [5], [6], [7], and led to more aggressive risk-management strategies in diabetes patients. This was a welcome development, given that diabetes confers a two- to fourfold risk increase for heart disease and stroke [8]. CVD prevention requires careful attention to physical-activity levels, dietary intake and appropriate use of cardioprotective medications [9].

However, diabetes may not only be a CVD risk equivalent in women, but may actually confer greater risk: in an updated analysis of the cohort examined by Haffner and colleagues [10], women with diabetes had higher rates of mortality than women with previous CVD. Although not all other investigators have identified such a gender difference, the updated analysis was consistent with studies suggesting that the relative risk increase for acute MI with diabetes is higher in women than in men [11], [12].

A relatively higher mortality for women with diabetes compared with those with prior CVD would suggest inadequate attention to CVD prevention in women with diabetes. While, a study using Framingham data reported declining mortality rates for both women and men with diabetes [13], an analysis of the US National Health and Nutrition Examination Survey (NHANES) data demonstrated declines in all-cause mortality over time for men with diabetes, but not for women [14]. Thus, the latter has highlighted a need to carefully examine gender differences in the effects of diabetes on mortality towards the goal of establishing appropriate preventative strategies in both women and men.

For this reason and returning specifically to the question of gender-specific differences in the context of diabetes and CVD ‘equivalence’, the present study has examined the totality of evidence through a systematic review and meta-analysis aiming to obtain gender-specific hazard ratios (HRs) by comparing diabetes and CVD patients in terms of all-cause, CVD and coronary heart disease (CHD) mortality.

Section snippets

Study selection

For our review, observational studies were identified that prospectively examined the mortality rates in individuals with diabetes, but without a prior history of CVD, that were compared directly with mortality in individuals with CVD, but without a previous history of diabetes. Our study also required that outcomes (such as all-cause, CVD and/or CHD mortality) be reported separately for women and/or men.

Literature search

Searches were performed (C.L.) with a medical librarian's assistance (A.C.), using three

Trial flow/flow of included studies

Nine studies were examined in detail and included (Fig. 1, Table 1). The PubMed search for previous meta-analyses assessing CVD risk in the context of type 2 diabetes or previous CVD generated 191 titles, among which one was deemed potentially relevant [16]. An updated search (August 1, 2009 to December 13, 2009) did not result in any additional primary research studies for inclusion, but did identify a second potentially relevant meta-analysis [17].

Previous meta-analyses

One previous meta-analysis [16] was published

Discussion

The present findings confirm that, in men, CVD and CHD mortality is lower with diabetes alone compared with previous CVD (CVD mortality HR: 0.82, 95% CrI: 0.69–0.98; CHD mortality HR: 0.73, 95% CrI: 0.65–0.83), while the all-cause mortality was similar with diabetes and previous CVD (HR: 1.02, 95% CrI: 0.93–1.12). In women, the paucity of studies has limited firm conclusions, but there is an indication that CVD, CHD and all-cause mortality may be higher with diabetes alone compared with

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Acknowledgements

We are grateful to Mr Patrick Belisle, MSc, of the Research Institute of the McGill University Health Centre, for performing the statistical programming for the meta-analyses, and to Ms Amanda Wilkins, BSc, BEd, also of the Research Institute of the McGill University Health Centre, for her administrative support.

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