European Journal of Obstetrics & Gynecology and Reproductive Biology
Menstrual and reproductive factors and risk of non-fatal acute myocardial infarction in Italy
Introduction
Sex differences in the molecular and cellular physiology of the heart and blood vessels have been reported in health and disease [1]. Female hormones, particularly estrogens, modify blood lipids and pressure, and various aspects of thrombosis, important correlates of cardiovascular disease [2]. Moreover, several recent works reported an association between timelife endogenous estrogen exposure and the risk of venous thromboembolism [3].
Epidemiological studies have reported a possible involvement of menstrual and reproductive factors in the aetiology of coronary heart disease [4], [5]. Among menstrual factors, younger age at menarche was weakly associated with coronary heart disease in at least two cohort studies [6], [7], but not in two case–control studies [8], [9]. In the Nurses’ Health Study [10] and in at least two case–control studies [8], [11] menstrual irregularity increased the risk of coronary heart disease.
The hypothesis that menopause and its biological modifications may be related to the risk of coronary heart disease derived from the observation that incidence and mortality rates for cardiovascular disease in pre-menopausal women are substantially lower than in men, but tend to approach those of men at older ages. Independent contributions to the increased risk by age and menopause have been suggested [2]; this is biologically plausible as menopause unfavourably alters the profile of some cardiovascular risk factors (such as levels of cholesterol, triglycerides, low-density lipoproteins and apolipoprotein-B), reduces levels of high-density lipoproteins and increases blood pressure [2], [4], [5]. The overall epidemiologic evidence on the relation between menopause and coronary heart disease is compatible with a moderate direct association between younger age at menopause and risk of coronary heart disease [4], [5], [12], [13], found only among smokers in the Nurses’ Health Study [14]. Controversial results were also found for hysterectomy, directly associated [15] or not related [16] with cardiovascular disease.
Among reproductive factors, the relation of coronary heart disease with parity has presented conflicting results [4], [5], [17], with most studies showing no significant relation, but others reporting increased risks [7], [18]. Early age at first birth has been associated with increased risk of coronary heart disease [9], or decreased risk [7], or no association [6], [8]. Women who had experienced at least one spontaneous or induced abortion had either increased or similar risk of coronary heart disease than women who had never had an abortion [5], [19].
In this paper, we analyzed the relation between menstrual and reproductive factors and the risk of non-fatal acute myocardial infarction (AMI), combining data of three case–control studies conducted in Italy.
Section snippets
Subjects and methods
Data were derived from a combined dataset from three hospital-based case–control studies, conducted in Italy, on risk factors of non-fatal AMI, defined according to the World Health Organization criteria [20].
The first study was conducted in 1983–1992 and included 314 women with AMI and 733 female controls [8]; the second one was conducted in 1988–1989 within the GISSI-2 study (Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto) and included 115 female cases and 130 controls [21];
Results
Table 1 gives the distribution of cases and controls according to age and other selected covariates. Compared to controls, cases smoked more cigarettes, were more frequently heavy alcohol and coffee drinkers, had higher body mass index and more often AMI in first degree relatives, and had more often a personal history of obesity, diabetes, hypertension and hyperlipidemia.
The relation of selected menstrual and reproductive factors with the risk of AMI is shown in Table 2. Compared to women with
Discussion
We found a slight direct association between the risk of AMI, irregular menstrual cycles and parity, which, however, did not increase with number of children. For both factors the association was apparently stronger, or restricted to pre-/peri-menopausal women and to current smokers.
Most limitations and strengths of this study are common to hospital-based case–control studies [23]. Cases were identified in the major general hospitals of the area, and in the control group only patients admitted
Acknowledgment
Partly supported by the Italian League Against Cancer.
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