Reproductive variables and subclinical vascular disease

Cardiovascular disease is the leading cause of death in both genders [1]. The implications of traditional cardiovascular risk factors like obesity, dyslipidemia and diabetes have long been recognized and prevention strategies applied worldwide [1]. The effect of obstetrical events, however, with regard to the development of cardiovascular disease in later life, is increasingly being recognized as a female-specific cardiovascular risk factor.

Gestational hypertension or preeclampsia represent a recognized risk factor for future hypertension [2]. Studies in mid-aged women with a history of preeclampsia, reported a direct association between carotid intima-media thickness (IMT), coronary atherosclerotic plaques and coronary artery calcium score compared to women who had normal blood pressure during pregnancy [2]. As described recently in the Study of Women’s Health Across the Nation, carotid CIMT is positively associated with a history of gestational hypertension and/or pre-eclampsia, with the unfavorable effect on the vessel walls being evident in late midlife [3]. Arterial stiffness, furthermore, increases during pregnancy in women with subsequent preeclampsia and small for gestational age fetuses compared to women with uncomplicated pregnancies [4].

Studies on the effect of gestational diabetes (GDM) on the development of subclinical vascular disease indicate a possible indirect adverse effect, mediated mainly by insulin resistance [2]. The exact pathophysiological link remains conflicting, with earlier studies describing positive associations between GDM and carotid IMT at the time of pregnancy and years thereafter [5]. More recent studies describe lack of association between GDM and indices of structural disease, but a positive link with arteriosclerosis, estimated by measures of brachial ankle pulse wave velocity at the time of menopause [3].

Research on the presence of subclinical vascular disease in women with preterm deliveries with small for gestational age babies or spontaneous abortions is still ongoing [6]. From the limited available data, women experiencing these obstetrical events seem to have greater risk for future cardiovascular disease and show evidence of subclinical atherosclerosis after delivery [6]. A recent study based on the UK biobank, however, did not identify an association between the history of spontaneous abortions and carotid IMT in women aged 40–65 years old with no previous diagnosis of cardiovascular disease [7].

On the contrary, breastfeeding seems to offer significant cardiovascular protection after delivery. Shorter duration of breastfeeding is related with greater extent of subclinical carotid atherosclerosis in later life [8,9]. Moreover, as recently described in the POUCHmoms study, breastfeeding of any duration is associated with a more favorable lipidemic profile and lower carotid IMT in women with a history of normotensive pregnancies. Unfortunately the protective effect of breastfeeding against the development of subclinical cardiovascular disease was not observed in hypertensive pregnancies [10]. In any case, breastfeeding is an excellent approach in managing the metabolic derangement of pregnancy, and women should be encouraged to breastfeed as long as possible.

From a pathophysiological perspective, many of the above-mentioned complications of pregnancy, like preeclampsia, preterm labor, delivery of small for gestational age infants or spontaneous abortion, are characterized by physiologic temporary transformations of the vessels linked with impaired vascular remodeling. These alterations develop over a shorter period of time, and are known as ‘acute’ atherosis, and consist of lipid deposition in vessel walls of the maternal spiral arteries leading to the placenta [11]. These vascular lesions have been found to exist rarely in normal pregnancies yet their prevalence may range between 1.2% in women with spontaneous preterm labor, 1.7% in women giving birth to babies small for gestational age, 2.5% in women experiencing spontaneous abortion, 9% in women with unexplained fetal death and up to 10.2% in women with preeclampsia [11].

In conclusion, the pregnancy-related conditions discussed above seem to accelerate the physiological process of vascular aging. Therefore, cardiovascular assessment should in general include a detailed obstetrical history, especially inquiring about hypertensive disorders of pregnancy, gestational diabetes and duration of breastfeeding [1,2]. Women with pregnancy – related adverse outcomes should receive regular cardiovascular screening including components of the metabolic syndrome. Evaluation of indices of subclinical atherosclerosis in these women should be restricted to research purposes as it is not of clinical benefit. Primary care physicians should recognize and manage the reproductive events analyzed above as ‘metabolic syndrome equivalents’ and encourage their female patients to control their body weight, quit smoking and adopt a healthy lifestyle.

Disclosure statement

No potential conflict of interest was reported by the author(s).