Menstrual and reproductive factors and risk of non-fatal acute myocardial infarction in Italy

https://doi.org/10.1016/j.ejogrb.2007.01.005Get rights and content

Abstract

Objective

We analyzed the relation between factors related to endogenous female hormones and the risk of acute myocardial infarction (AMI).

Study design

We used a combined dataset from three Italian case–control studies, including 609 women with non-fatal AMI and 1106 controls hospitalized for acute conditions.

Results

The odds ratios (OR) of AMI were 1.36 (95% confidence intervals, CI 0.95–1.96) in women with an irregular menstrual pattern compared to a regular one, and 1.45 (95% CI 1.07–1.97) in parae compared to nulliparae, without linear trend in risk with number of children. No relation was found with menopausal status, age at menarche and menopause, abortion, and age at first and last birth. Compared to women without abortions the OR was 0.84 (95% CI 0.60–1.18) for >1 abortion; compared to women without spontaneous or induced abortion, the ORs were 0.92 (95% CI 0.62–1.38) for >1 spontaneous and 0.63 (95% CI 0.36–1.08) for >1 induced abortion. The association of parity and irregular menstrual cycles was stronger in pre-/peri-menopausal women and in current smokers. Compared to nonsmokers with regular menstrual cycle, the OR was 5.98 (95% CI 3.38–10.56) for smokers with irregular one, and compared to nonsmokers nulliparae the OR for smokers parae was 4.77 (95% CI 3.12–7.29).

Conclusions

Irregular menstrual cycles and parity were related to increased AMI risk, mainly among pre-/peri-menopausal women and among smokers.

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.

References (30)

  • G.A. Colditz et al.

    A prospective study of age at menarche, parity, age at first birth, and coronary heart disease in women

    Am J Epidemiol

    (1987)
  • G.S. Cooper et al.

    Menstrual and reproductive risk factors for ischemic heart disease

    Epidemiology

    (1999)
  • C. La Vecchia et al.

    Risk factors for myocardial infarction in young women

    Am J Epidemiol

    (1987)
  • J.R. Palmer et al.

    Reproductive factors and risk of myocardial infarction

    Am J Epidemiol

    (1992)
  • C.G. Solomon et al.

    Menstrual cycle irregularity and risk for future cardiovascular disease

    J Clin Endocrinol Metab

    (2002)
  • Cited by (39)

    • Association between age at menarche and cardiovascular disease: A systematic review on risk and potential mechanisms

      2017, Maturitas
      Citation Excerpt :

      Of these four studies, the longitudinal Nurses’ Health Study [19] showed an inverse linear relation between AAM and nonfatal MI and death due to CHD, with a rate ratio of 0.6 (95% CI 0.3–1.1) for an AAM of 15 years, compared to an AAM of 13 years. In total, two other studies reported a U-shaped relation between AAM and (A)MI [20,21], but none of the effect estimates reached statistical significance. In the Women’s Ischemia Syndrome Evaluation (WISE) cohort study a mean AAM of 12.9 years (95% CI 12.6–13.2) was found for women with obstructive CAD, while women who did not have obstructive CAD had a mean AAM of 12.6 years (95% CI 12.4–12.8) [22].

    • Reproductive History of Women With Takotsubo Cardiomyopathy

      2016, American Journal of Cardiology
      Citation Excerpt :

      Cardiovascular changes associated with pregnancy are so vast that they led some investigators to define pregnancy as a “9-month-long cardiovascular stress test.”24 A secondary analysis from 3 case-control studies has shown that parity was positively associated with an increased risk of nonfatal MI,25 whereas a prospective analysis from the Multi-Ethnic Study of Atherosclerosis cohort found that the number of live births was associated with increases in left ventricular mass and end-diastolic and end-systolic volume and decreases in ejection fraction in middle to older age, independent of demographic and CHD risk factors.26 Although ours is the first study showing a significant association between number of pregnancies and TC, this finding deserves further study, in particular as to how repeated pregnancies may predispose women to develop TC later in life.

    • Can premenstrual syndrome affect arterial stiffness or blood pressure?

      2012, Atherosclerosis
      Citation Excerpt :

      Although, due to these limitations, the results of this study should be regarded as hypothesis generating, several novel clinical implications arise which should trigger further research. Recent evidence suggests that quantitative irregularities in the menstrual cycle and parity characteristics may be related to increased acute myocardial infarction risk, mainly among pre-/peri-menopausal women and among smokers [30]. Whether qualitative irregularities in the menstrual cycle such as PMS affect cardiovascular risk has not been assessed so far, but this is the first data supporting this hypothesis.

    • Risk of cardiovascular disease among postmenopausal women with prior pregnancy loss: The women's health initiative

      2014, Annals of Family Medicine
      Citation Excerpt :

      These guidelines, however, did not address the long-term cardiovascular implications of miscarriage. A limited number of studies have evaluated pregnancy loss and risk of development of future CVD, but the findings have been inconsistent, with some finding no clear association11,12 and others suggesting an increased risk between pregnancy loss and CVD.3,10,13,14 The Women's Health Initiative (WHI) population provides a unique opportunity to be able to examine the association of miscarriage and stillbirth in a diverse, geographically dispersed cohort of women with adjudicated cardiovascular events, including fatal and nonfatal myocardial infarctions and stroke outcomes.

    View all citing articles on Scopus
    View full text