Smoking
No exposure to tobacco in any form
Diet
Low in saturated fat with a focus on wholegrain products, vegetables, fruit and fish
Physical activity
At least 150 min/week moderate aerobic PA (30 min for 5 days/week) or 75 min/week of vigorous aerobic PA (15 min for 5 days/week) or a combination thereof.
Body weight
BMI 20–25 kg/m2, waist circumference <94 cm (men) or <80 cm (women)
Blood pressure
<140/90 mmHg (lower in most patients with DM, younger age groups and in very high risk patients)
Lipids primary targets
LDL-C
HDL-C
Triglycerides
Very high risk: < 1.8 mmol/L (<70 mg/dL)
High risk: < 2.6 mmol/L (<100 mg/dL)
Low to moderate risk: < 3.0 mmol/L (<115/mg/dL)
No target, but >1.0 mmol/L (>40 mg/dL) in men and >1.2 mmol/L (>45 mg/dL) in women
No target, but <1.7 mmol/L (<150 mg/dL) indicates lower risk and higher levels indicate a need to look for other RF.
Diabetes
HbA1c <7% (<53 mmol/mol)
Genetic Predisposition: Strong Risk Factor for Premature CVD in Women
Systematic collection of family history of premature CVD death (<60 years) to routine cardiovascular risk assessment is an important additive tool in improving risk estimation [43–45]. Coronary artery calcium (CAC) scores are higher in families with premature CAD and especially in women [46, 47]. In patients with premature ACS, a positive family history has been shown to be associated with greater severity of CAD at angiography [48]. The risk increases with younger age of events/death and the number of affected first relative(s) [44, 49, 50]. It is therefore important to assess family history more detailed than only in a binary yes or no. Several studies have shown that a positive family risk is an even stronger risk factor for women than for men [47, 51]. Also, women with repeated pregnancy losses and hypertensive pregnancy disorders more often have an increased family risk for CVD compared to women after normal pregnancies [52–55]. Patient A, with premature symptomatic hypertension illustrates the importance of a positive family risk and a previously complicated obstetric history.
Gender-Shift in Prevalence of Traditional Risk Factors During Life-Course
At younger age men have a more adverse CVD risk profile, while after 65 years of age women have relatively more clustering of risk factors [16, 41, 56]. There is apparently an important gender-shift in CVD risk between 45 and 65 years of age when women have their menopause transition. It is therefore crucial not only to consider risk factors in relation to sex, gender and ethnicity, but also to the phase in life of the individual patient. Moreover, different interactions exist between women and men among the various CVD risk factors during our lifecycle [57]. This is not taken into account in the large number of prediction models that are currently available [58]. The 2013 ACC/AHA prevention guidelines atherosclerotic cardiovascular disease (ASCVD) now use the contemporary risk algorithm for improved prediction in an increasingly ethnically heterogeneous population [59]. In women, many traditional risk factors (dyslipidemia, hypertension, insulin resistance) change in an adverse direction between 50 and 60 years of age, making it necessary to reconsider these factors when they are in their late fifties/early sixties. Table 1.2 illustrates important gender differences in weighting of traditional risk factors during middle-age.
Table 1.2
Sex differences related to traditional CVD risk factors
Risk factor | Women | Men |
|---|---|---|
Age-threshold increased CVD risk | ≥55 years | ≥45 years |
Family risk premature CVD | First degree <65 years | First degree <55 years |
Smoking | 2× elevated RR ACS < 55 years | Most important RF < 50 years |
Total Cholesterol | 10% increase after menopause | Stable after 50 years |
HDL-cholesterol | ≥1,2 mmol/L | ≥1.0 mmol/L |
LDL-cholesterol | 14% higher after menopause | No change after 50 years |
Diabetes mellitus | 1.5–2.0× higher RR mortality risk than in men Independent RF for HFpEF | CVD mortality <lower than in women |
Cardiovascular Risk Age and ‘lifetime’ Risk for Cardiovascular Disease
Young women (<55 years) at increased risk for CVD have a low absolute risk for a relatively short-term cardiovascular event in risk charts such as the SCORE, which is commonly used in Europe. This may lead to serious undertreatment of lifetime risk and irreversible longterm cardiovascular damage. In 2007 a relative risk chart has been developed to compare the actual risk with the ‘ideal’ risk of that age, e.g. higher relative risk (RR) in young female smokers than in non-smokers [60]. This has been changed into the more appropriate ‘cardiovascular risk age’ in the 2012 and 2016 updated version of the ESC CVD prevention guidelines [41, 42]. The risk age of a person with several cardiovascular risk factors is the age of a person with the same level of risk but with ‘ideal levels’ of risk factors. Thus, a high-risk 40 year old woman, such as a heavy smoker, may have a risk age of ≥60 years. This illustrates the likely reduction in life expectancy for a young person with a low absolute but high RR of CVD if preventive measures are not adopted. Risk age is automatically calculated in the latest revision of HeartScore (www.HeartScore.org). An important improvement of the 2016 ESC SCORE charts is a better recognition of disease risk in younger age-groups, in women and in diabetics [42].
For women it may also be important to focus on 30-years ‘lifetime’ risk of all manifestations of CVD and not solely on 10 years risk of IHD [60, 61]. At older age, the risk of strokes and heart failure is higher than for ACS. Adding signs of subclinical atherosclerosis by using the CAC score to risk factor assessment, significantly improves risk prediction, which is especially important for younger women [42, 62–65]. In the UK National Institute for Health and Care Excellence (UK–NICE) guidelines measurement of the CAC score in intermediate risk patients has now been added to the guidelines in patients with symptoms of angina [66].
Dyslipidemia and Statin Use in Women
Low HDL- cholesterol is a stronger CVD risk factor in women than men, with values that remain stable or decline somewhat during menopause transition [67]. In contrast, between 45 and 60 years of age, total cholesterol and LDL cholesterol levels rise about 10–14% in women, while there is no significant change in men [68–70]. Figure 1.1 outlines the change in total cholesterol levels (male/female) with ageing derived from a Dutch population-based cohort [67]. In Fig. 1.2 pre-and postmenopausal lipid values are depicted. While the beneficial effects of secondary prevention with statins in women are beyond any doubt [71], their efficacy in primary prevention is controversial [72–75]. This is caused by an under-representation of women in clinical trials, a lack of sex-specific analyses and a too young age at inclusion of participating women. In the MEGA-study it was shown in 5300 women that primary prevention with a statin for mild hypercholesterolemia (Total cholesterol 5,7–7,0 mmol/L) is useful upward of 55–60 years of age, when CVD risk increases and more combined risk factors are present [76]. This has also been an important consideration in the JUPITER-trial, which included 11.001 men ≥50 years and 6801 women ≥60 years at intermediate CVD risk [71, 77]. In a recent meta-analysis of the Cholesterol Treatment Trialists’ (CTT) Collaboration database, no difference was found in the effectiveness of statins in men and women at an equivalent risk of CVD [78]. This is in agreement with the current ESC guidelines CVD prevention, which are less strict than the 2013 ACC/AHA guidelines for the prevention of dyslipidemias [41, 79–81]. According to the UK-NICE guidelines, the majority of men over 50 years and more than half of all women over 60 years, having a 10% CVD risk over 10 years, will qualify for statin use in primary prevention [82].
Fig. 1.1
Age/gender related changes in total cholesterol levels. Doetinchem-cohort and REGENBOOG-project [67]
Reported side-effects of statins vary among populations, ranging from 5 to 25%, and mainly consist of muscle symptoms such as myopathy, myalgia and weakness [83–85]. Discontinuation of medication occurs more often in real life than in clinical trials [86]. The majority of patients report statin-associated muscle-related adverse effects within the first 3 months of initiating therapy [87]. Women report more adverse symptoms than men, which is a serious reason for their lower adherence to therapy [88–91]. It may be difficult however to ascertain whether symptoms of muscle pain are indeed related to statin use or to other causes [92]. Fatigue, fibromyalgia and arthrosis-related (inflammatory) symptoms are quite common in middle-aged women [93, 94]. A contributing mechanism to explain the increased susceptibility for side effects of statins in women is their interaction with CYP3A4 inhibitors [95]. Besides, other causative factors for myopathy are related to certain genetic variants and an interaction with mitochondrial function [96–98]. The negative publicity in the lay press has led to the biased expectation that statin use is harmful [99]. Early statin discontinuation in patients with an appropriate indication for it use increases the risk of ACS and cardiac death [85, 100]. Therefore, health-care providers should re-challenge more often with other statins whenever possible, or perhaps start with a lower dose, while putting the side-effects on muscle into perspective by appropriate counseling and shared decision making [101, 102]. According to the advice of the European Atherosclerosis Society (EAS) intake on alternating days or twice a week may also be a pragmatic option [103]. Noteworthy is that the attitude towards chronic medication use and preferences for complementary and alternative medicines may be different among both genders [104]. Although PCSK9 inhibitors (monoclonal antibodies) are very effective in reducing LDL-cholesterol in statin-intolerant patients, its (expensive) use is at first being restricted to patients with primary hypercholesterolemia or mixed dyslipidemias who are not adequately controlled with statins. Long term efficacy and safety data are not yet available and the cost-effectiveness of these new agents in patients with heterozygous FH or ASCVD do not meet the currently generally acceptable criteria [105, 106].
Treatment of Hypertension in Women
Blood pressure levels show important gender differences during lifetime and the long-term consequences of hypertension for the development of atrial fibrillation, left ventricular hypertrophy and heart failure with preserved ejection fraction (HFpEF), which are worse for women than for men [107]. Hypertensive women develop more vascular and myocardial stiffness than men at old age, and more often have isolated systolic hypertension, reflecting aortic stiffness [108, 109]. The diameter of the aorta increases with age, more in men than women, wherefore gender-specific and age-adjusted normal values are needed [110]. In developed countries 30% of adult individuals have hypertension and this number is even higher in low-middle income countries, reaching up to 53% of all women [111, 112]. For every 20 mmHg SBP and 10 mm Hg DBP increase in BP, there is a doubling of mortality both from IHD and stroke for subjects aged 40–89 years [113]. In the EUROASPIRE III study women were less well treated for their hypertension than men and considering the results of EUROASPIRE IV, which again demonstrated that blood pressure is often not optimally controlled, there is still room for improvement [19, 20]. Although younger women are at lower absolute cardiovascular risk than elderly women, this should not impede the detection and effective management of hypertension within each age category. After the results of the Systolic Blood Pressure Intervention Trial (SPRINT) –trial it is expected that treatment goals for hypertension will become more strict and age-dependent [114, 115]. Many symptoms may accompany elevated blood pressure, such as headaches, palpitations, tiredness and chest pain, for which physicians should be alert (see patient A and Chap. 5).
Diabetes Mellitus: Mind the Consequences in Women
With the rise in the number of low physical activity and overweight/obese individuals, the prevalence of type II diabetes (T2DM) is increasing. Treatment of T2DM in women used to be less optimal than in men, but disparities in care are getting smaller [19, 116–118]. After adjustment for their higher clustering of risk factors, women with T2DM still have a twofold increased CVD risk than men [119–122]. They also have more signs of inflammation and more unfavorable changes in coagulation and endothelial function leading to a greater cardiometabolic risk factor load [123, 124]. In addition, the pattern of IHD and the occurrence of vascular and myocardial stiffening with ageing also shows important gender differences that affect outcomes negatively [125]. Diabetic women have a more diffuse and non-obstructive pattern of coronary artery disease (NOCAD) than men, with higher rates of coronary microvascular dysfunction (CMD) which is more difficult to diagnose and to treat than focal obstructive CAD in the epicardial coronary arteries. Hypertension and T2DM are strongly and inversely related risk factors for CVD in postmenopausal women [126]. Moreover, T2DM is an independent risk factor for the development of HFpEF in women, which often remains unrecognized in clinical practice [127, 128]. An echocardiography study in patients with T2DM over 60 years of age showed that 28% of women and 18% of men had previously unknown signs of HFpEF [128]. Both type I and type II diabetes promote inflammation which affects both genders differently and also show differences among pre- and postmenopausal women [129–133]. Adverse outcomes of pregnancy are associated with both types of diabetes and there is evidence to suggest that women with diabetes undergo earlier menopause than women without diabetes [134, 135]. The 2013 ESC guidelines on diabetes, pre-diabetes and CVD extensively describe very relevant aspects of this subject, but are importantly lacking a gender-specific viewpoint [136]. Longterm follow-up data from the Rancho Bernardo study showed that women with diabetes and angina had a three-to four-fold greater risk of dying from CHD than women who had diabetes without angina, independent of covariates [137, 138]. There were no independent associations found in men. In 2015 the AHA has released a scientific statement on the current knowledge of gender differences in the ASCVD consequences of diabetes, with a stronger relative mortality risk in women than in men [139]. This also concerns stroke and PAD [138, 139]. There is growing evidence that the MetS and diabetes are also associated with an increased prevalence of breast cancer in women with more adverse outcomes [140, 141].
In asymptomatic patients (male/female) with T2DM a high coronary artery calcium score (CAC) has been shown to be an important predictor of adverse CVD events [142]. As women with T2DM often have a diffuse pattern of CAD with concomitant coronary vascular dysfunction and HFpEF in the elderly, symptom recognition of IHD can be difficult. Patient B is an example of a high risk T2DM female patient (family, gestational diabetes, early menopause, premature hypertension) with recurrent angina symptoms which were poorly recognized as being related to CMD.
Several studies have compared the effectiveness of PCI versus coronary artery bypass surgery (CABG) in patients with T2DM and multi-vessel CAD [143–146]. In all studies it was found that CABG provides better longterm outcomes in male and female diabetic patients. Although women with diabetes are less likely to be referred for CABG, this is a class I therapeutic recommendation in diabetic patients (male/female) with stable IHD [147].
Female-Specific Risk Factors: Tools to Identify Young Women at Higher Risk
Sex-specific factors related to hormonal and reproductive status are known to relate to CVD risk. It is unclear yet, to which extent and within which stage(s) of life these female-specific risk factors are relevant to CVD risk estimation in women. When considering all age-groups together, reproductive and pregnancy related disorders do not seem to be relevant in 10 years risk estimation [148, 149]. However, when focusing on younger patients (<55 years) evidence is increasing that assessment of female-specific risk factors may indeed add to identify women at higher risk [51, 150, 151]. This is especially important as young women are considered to be at low risk, until a first premature event has occurred. Reproductive and pregnancy-related factors may predispose to earlier signs of endothelial dysfunction, vascular inflammation and atherosclerosis [152–154]. This is less relevant for the older female population, having a higher prevalence of traditional risk factors with more advanced and more easily detectable atherosclerosis. It is to be expected that a combination of genetic risk together with (several) female-specific reproductive and non-traditional risk factors related to inflammatory diseases are more predictive in identifying women at high risk for premature CVD, than one or two single factors alone [150]. In Fig. 1.3 several female-specific risk variables and non-traditional risk factors to identify potentially high risk women are depicted, see also the patient cases in this chapter. The justified weighting of these various risk variables remains to be further investigated.
Fig. 1.3
Vascular damage after hypertensive pregnancy disorders. Adapted from Sattar & Greer 2002 [192]
Age at Menarche
Over the past decades there has been a shift in age at menarche (first menstrual period) from ≥12 years towards younger ages. Early age at menarche (8–12 years) has been associated with increased body mass index (BMI), higher risk of MetS, T2DM and more CVD risk factors in adolescent girls and in young women studied up to age 40 year [155–159]. The association of age at menarche and CVD risk is only partly mediated by adiposity [160]. In a recent large study a more U-shaped association was found between age of menarche and IHD [161]. As late menopause is protective for CVD, the timing of estrogen exposure in the reproductive years may be more important than the total number of years of estrogen exposure [162]. In more than fifty percent of women the onset of menarche is caused by a combination of environmental and genetic factors of which more than 30 genetic loci have been identified [163–165]. Sufficient data are currently lacking to determine the value of age at menopause in individual risk prediction.
Polycystic Ovary Syndrome (PCOS)
Polycystic ovary syndrome (PCOS) is a complex disorder characterized by oligomenorrhea, amenorrhea, hyperandrogenism, and polycystic appearance of the ovaries [166]. It is the most common hormonal imbalance among females of reproductive age, affecting up to 10–13% of women [167]. Ovulatory dysfunction in women with PCOS is associated with low grade inflammation and an increased cardiometabolic risk [168]. This promotes endothelial dysfunction, independent of obesity, age and other risk factors [169]. Women with PCOS are at substantially increased risk of developing T2DM [124, 170]. The risk for hypertension and dyslipidemia is also moderately increased compared to women without PCOS. Long term data on CVD outcomes are relatively scarce and cardiovascular and metabolic risk profiles are hampered by the heterogeneity of PCOS phenotypes [171–173]. It is controversial that PCOS women with excess androgen production are at high future CVD risk [174]. Several studies have shown that women with PCOS are at 22% to a twofold increased risk to develop GDM in pregnancy [175, 176]. The Dutch guideline cardiovascular risk management after reproductive and pregnancy-related disorders therefore recommends that women with PCOS should be screened for gestational diabetes (GDM) during pregnancy [177]. When evaluating female patients for their CVD risk it is important to ask about irregular menses and if needed to screen for PCOS by a gynecologist [172]. Women with PCOS should be encouraged to optimize modifiable cardiovascular risk factors such as obesity to reduce their future CVD risk.
Gestational Diabetes (GDM)
Gestational diabetes mellitus (GDM) occurs in 2–10% of pregnancies and confers a 4- to 7-fold higher risk of future type II and the development of the MetS in midlife [178, 179]. Several studies have reported a 66–85% higher risk of CAD, myocardial infarction, and stroke after previous GDM [180]. Women with GDM also have a 1.5 times greater likelihood to develop hypertensive pregnancy disorders (HDP) compared to women without GDM [181]. It is recommended that women with prior GDM receive education about lifestyle modification and regular (yearly) testing for glucose intolerance, since these women are at high risk to develop T2DM [182–184].
Premature Ovarian Insufficiency and Menopause: See Chap. 5
Repeated Miscarriages and Hypertensive Pregnancy Disorders: “stress-test” in Women
In multiple large population-based studies is has been shown that recurrent (≥2) miscarriages convey an increased risk for IHD and other types of CVD [53, 55, 185, 186]. These also occur more often in women having an increased family risk for ASCVD [55]. Spontaneous preterm delivery is also an independent risk factor for the development of IHD, stroke and overall CVD [187]. In high-income countries hypertensive pregnancy disorders (HPD) affect 10% of all pregnancies and account for the majority (16%) of maternal deaths. These are most frequently present in first pregnancies, with a high recurrence rate in subsequent pregnancies. There are several manifestations of HPD, according of the timing and severity of the blood pressure disorders during pregnancy (pregnancy-induced hypertension, early-onset preeclampsia or late-onset preeclampsia) [188]. An uncertain percentage of women has preexisting premature hypertension before conception. Preeclampsia, especially when occurring early in pregnancy, is the severest manifestation of HPD and may degenerate into the Hemolysis Elevated Liver enzymes and Low Platelets (HELLP) syndrome with severe metabolic, vascular and thrombotic complications in the mother [52, 189]. This often results in fetal growth retardation and intrauterine death of the fetus. A low birth weight is an important and reliable indication for the severity of the preeclampsia, which most women are able to recall later in life and thus may be a helpful tool in clinical practice. Worldwide, preeclampsia occurs in 3–5% of pregnancies, defined as de novo blood pressure elevation ≥140/90 mmHg with proteinuria ≥0.3 g/24 h after the 20th week of gestation [190]. In normal pregnancy several components of the metabolic syndrome are temporarily elevated, such as insulin resistance, lipid levels, and coagulation and inflammatory factors. It is hypothesized that normal pregnancy itself stimulates an inflammatory response, which is exaggerated in preeclampsia, and involves dysfunction of the endothelium in the uterine circulation (Fig. 1.3) [191, 192]. The ultimate source of the inflammatory stimulus is presumably the placenta itself. Uteroplacental arterial insufficiency may cause the release of inflammatory stimuli (cytokines) into the maternal circulation, leading to vasoconstriction and activation of the coagulation system. Women after HPD are at increased risk for future CVD, which is strongly related to the timing and severity of the hypertensive disturbances [193–198]. The cardiovascular risk profile after pregnancy importantly reflects the risk of hypertension and CVD later in life [199]. Around 43% of women after early preeclampsia already have hypertension before the age of 40, which is on average 7.7 years earlier than in women with previous uncomplicated pregnancies [54, 184]. In more than 75% of affected women a positive family history for CVD is reported. More arterial stiffness and a higher prevalence of cerebral white matter lesions are also found in women after preeclampsia compared to women after normotensive pregnancies [200–202]. Women after HPD have signs of earlier ovarian ageing as an indication of impaired vascular health [203].
During normal pregnancy, several metabolic factors are temporarily increased such as insulin resistance, lipid levels, as well as coagulation and inflammatory factors [52, 204]. In women who develop HPD or GDM, this physiological response is disturbed, leading to vascular endothelial dysfunction in both the uterine and maternal circulation [192, 205]. Insufficient placentation may be caused by genetic, immunological, vascular and environmental factors and has many pathophysiological mechanisms in common with the initial process of atherosclerosis [204, 206]. Many circulating biomarkers during HPD remain detectable for many years, even decades afterwards [207–209]. These promote early endothelial dysfunction and premature onset of atherosclerosis in the mother [210].
Clinical Symptoms and Treatment Advise in Women After Preeclampsia
Many young women have a variety of symptoms after preeclampsia, that are often not well recognized, but may result in a reduced quality of life [211]. Previously affected women may even state that ‘they never have recovered to normal’ after their pregnancy (Patient C). Persistent symptoms of fatigue, concentration disturbances and impaired mental well-being may contribute to lower social functioning [212, 213]. In others premature (subclinical) manifestations of CVD may occur within several years after index pregnancy (Patient D). Early preeclampsia is associated with slightly higher levels of depressive symptoms and fatigue on average 14 years after index pregnancy compared to previously unaffected women, but its clinical relevance is not clear yet [214]. It has also been found that during menopause transition women after HPD have an enhanced sympathetic nervous activity which may be associated with more disabling vasomotor symptoms [215]. These preliminary findings will need more attention in future research
Thus far, longterm follow-up intervention studies to prevent CVD after high risk pregnancies are lacking. Preeclampsia has now been adopted as a female-specific risk factor in several guidelines, such as the 2011 AHA prevention guideline in women, the 2014 AHA stroke prevention guideline, the 2016 Dutch guideline cardiovascular risk management after reproductive and pregnancy-related disorders, and the 2016 ESC guidelines CVD prevention [40, 42, 182, 187]. First measure after index pregnancy is adherence to a healthy diet- and lifestyle onwards. It remains to be investigated whether early and strict lowering of blood pressure and cholesterol (if appropriate) may prevent the early occurrence of CVD in these potential high risk women [216].
Non-traditional Risk Factors in Women: Co-morbidity with Inflammatory Disorders
An increased CVD mortality risk has been found in patients with rheumatic and endocrine disorders such as rheumatic arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) and thyroid disorders which are more prevalent in women than in men [217–219]. Chronic systemic inflammation itself can be considered as an independent CVD risk factor, but patients with these disorders also have a higher clustering of traditional risk factors which may increase their susceptibility for premature CVD [220]. There are important sex-related differences in immune reactivity, with a relatively increase in women during/after menopause transition [129]. Coronary microvascular dysfunction (CMD) may be the key mechanism involved in accelerated atherosclerosis in chronic inflammatory diseases [221, 222]. Of interest is that women with lichen sclerosis (LS) also have a higher susceptibility for autoimmune disorders such as alopecia areata, vitiligo, thyroid disease and pernicious anemia [223]. Women with CMD regularly report to have concomitant LS, which should be further explored. The main cause of CVD deaths in RA patients is ischemic heart disease (IHD), with a higher ACS related mortality risk compared to the general population [224–227]. The presence of rheumatologic disorders is independently associated with worse outcomes after PCI [228]. It remains to be investigated whether frequently used anti-inflammatory biological agents may also have beneficial anti-atherogenic effects.
Migraine
Until recently, only migraine with aura has been found to be associated with an increased CVD risk in women [229, 230]. In a 20-years follow-up study among participants of the Nurses’ Health study however, a consistent increased risk (HR 1.50, CI 1.33–1.69) for cardiac and cerebral manifestations of CVD was found [231]. More than 15% of women had (previous) migraine, which occurs 3–4 times more often in women than in men. Migraine is related to an increased family risk for CVD, premature vascular dysfunction, a higher susceptibility for thrombosis and inflammation (Fig. 1.4) [232, 233]. Several studies have also demonstrated significant associations between migraine and celiac disease, inflammatory bowel disease, and irritable bowel syndrome (IBS) [234]. The case of patient E illustrates the complex co-morbidity of migraine, T1DM, inflammatory diseases and premature CVD.
Fig. 1.4
Female-specific and non-traditional risk factors: Risk variables for early endothelial dysfunction/premature CVD. PCOS polycystic ovary syndrome, HPD hypertensive pregnancy disorders, HELLP hemolysis elevated liver enzymes low platelets syndrome, GDM gestational diabetes mellitus, CMD coronary microvascular dysfunction, VMS vasomotor symptoms, ACS acute coronary syndromes, CVD cardiovascular disease
Know and Manage Your Numbers!
Women with an elevated family risk for CVD should be aware of their CVD risk factors and aim to a healthy lifestyle from early years on. Self-management of blood pressure with modern eHealth applications is less time-consuming than regular office visits and actively involves patients as partners. This may also increase motivation for lifestyle and medication adherence [235]. Recent studies have shown that self monitoring of blood pressure improves treatment outcomes with lower costs compared to office-based therapy [236, 237].
Key Issues
Clinical manifestations of CVD appear 7–10 years later in women than men
Smoking and increased family risk are important risk factors in women with premature CVD
Premenopausal women have a lower CVD risk than similarly aged men
At old age women have a higher clustering of CVD risk factors than men
T2DM has a higher relative CVD mortality risk in women than in men
Female specific risk variables may be helpful to identify women at increased premature ASCVD risk
HPD and especially preeclampsia/HELLP are important risk factors in women
Migraine and (autoimmune) inflammatory and rheumatic disorders promote early endothelial dysfunction and are more prevalent in women than in men
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