Women, diabetes and coronary heart disease

Abstract

Aims: The aim of the present study was to explore the reason why women with diabetes lose the female protection against MI, by investigating cardiovascular risk factors, markers of inflammation, early predictors for future development of diabetes and clinical manifestations in diabetes and coronary heart disease.Subjects and methods: Women with (n=29), and without diabetes (DM) (n=64), hospitalised with a smyocardial infarction ( MI) 1994-96, were compared with DM-women without MI (n=46) and healthy controls (n=125). They were invited to a screening examination with questionnaires, physical examination and blood sampling (Paper I). Furthermore, titers of antibodies to malondialdehyde-treated LDL (oxLDL), and CRP levels, as a measure of the immune response and inflammation, were assessed. (Paper II). In addition, 1351 women, aged 39-65 years, without prior DM or CVD, took part in a screening investigation in 1979-81 with questionnaires, physical examination and blood sampling. Development of DM up to 1998 was identified at a second screening 1997-98 (Paper III). Finally, we investigated the influence of DM on clinical presentation, in-hospital course, and short-term prognosis in 6488 men (21.2 % DM) and 2809 women (28.7% DM) ¡Ü 80 years old who were prospectively enrolled in the Euro Heart Survey of Acute Coronary Syndromes (ACS) (Paper IV).Results: Women with prior MI had, compared with DM women without MI, significantly higher waist/hip ratio, and very high s-triglycerides (TG) and low HDL-cholesterol levels. They also had higher p-fibrinogen, were smokers and lived a sedentary life to a higher degree than the other women. The women with DM and/or MI had higher IgG and lower IgM titers of antibodies against oxLDL and higher CRP levels than the healthy controls. S-TG, overweight, high blood pressure (BP) and low physical activity significantly increased the risk of future diabetes. Even slightly elevated s-TG resulted in a considerably enhanced risk of DM, which was independent of the other factors. Women with DM and ACS were more likely to present with ST-elevation ACS, to develop Q-wave MI, and had higher mortality than non-DM women, whereas the differences were smaller in men. The interaction between sex and DM was significant.Conclusions: Women with DM who have manifested a MI carry a very substantial CVD risk factor burden. A pronounced inflammation and differentiated immune response against modified LDL might result in a more aggressive atherosclerotic process in women with DM and/or MI. Even slightly elevated TG levels and moderately increased BP and overweigt have a strong influence on DM risk, independent of other factors. Women with ACS are more likely to with ST-elevation ACS, develop Q-wave MI, and have worse prognosis than non-DM women, whereas the differences in men are less pronounced. The results underscore the importance of implementing evidence based primary and secondary preventive measures. They also suggest a differential effect of diabetes on the pathophysiology of ACS based on the patient¡¯s sex and emphasize the importance of analyzing men and women with DM separately.