HTN is a highly prevalent and powerful CVD risk factor in both women and men that is associated with myocardial infarction, heart failure, stroke, atrial fibrillation, peripheral vascular disease, and chronic kidney disease. Systolic blood pressure begins to increase around the time of transition to menopause in women and becomes more prevalent after 65 years of age in women compared to men. In addition, studies have found that the risk of HTN is higher in women than men [12, 13, 14]. Young women with HTN are at greater risk of end-organ damage compared to age-matched men [15]. Arterial stiffness, autonomic dysfunction, generalized endothelial dysfunction, and upregulation of the renin-angiotensin system all contribute to these increases in blood pressure in the setting of declining estrogen levels [16]. African American (AA) women are more likely to have HTN diagnosed at younger ages and have more severe HTN compared to white women [17]. In addition, AA women have nearly twice the age-adjusted death rate attributable to HTN, although this and other CVD risk factors are often undertreated in AA women. A recent community-based CVD risk factor screening study in 945 AA women found that elevated blood pressure and obesity were prevalent at younger ages [18]. Older and AA women are particularly susceptible to increased risk from heart failure, stroke, and renal disease due to HTN [19]. Women are also more likely to have anxiety-related and “white coat” HTN compared to men [20, 21]. Current HTN guidelines recommend avoiding the use of oral contraceptives in reproductive-age women with uncontrolled HTN seeking contraception and instead recommend using low dose ethinyl estradiol, progestin only formulation, or alternative methods such as an intrauterine device [14].

Diabetes mellitus remains one of the most prevalent diseases in the United States with an estimated one in nine women having this condition [22, 23]. The inflammation and atherogenesis associated with diabetes results in an increased risk of CVD [24, 25, 26]. Diabetic women have a 3–7 times increased risk of developing heart disease compared to a 2–3 times increased risk in diabetic men [27, 28, 29, 30]. The greater impact of diabetes on women may be partially due to increased adiposity [31]. Women are more likely than men to progress from prediabetes to diabetes [32]. In the original cohort of the Framingham Heart Study, there was a strong, independent association between HgA1c and CVD in women, but not in men. For every 1% increase in HgA1c, the relative odds for CVD increased by 1.39 in women [33]. The strong association in women between hyperglycemia and CVD remained significant even when women who were classified as diabetics were excluded [33]. In a meta-analysis, the rate of fatal coronary heart disease was higher among patients with diabetes compared to those without diabetes (5.4% vs. 1.6%) [27]. However, the difference was more pronounced in diabetic vs. non-diabetic women (7.7% vs. 1.2%) compared to diabetic vs. non-diabetic men (4.5% vs. 2.0%) [27]. Women with diabetes had a higher relative risk of fatal coronary heart disease compared to diabetic men (3.5 vs. 2.0 respectively) [27]. Menopause results in additional risk factors for CVD [27]. Although there does not seem to be a correlation between the onset of menopause and higher glucose levels, an increased risk of metabolic syndrome emerges after the transition to menopause, beyond the risk attributable to age alone [34, 35, 36]. Early diagnosis of diabetes is essential, particularly in racial/ethnic groups at high risk for diabetes such as AA, Hispanics, American Indians, and Pacific Islander Americans. While glucose-lowering therapy reduces microvascular complications, randomized trials have not shown a benefit of intensive glucose lowering on CVD outcomes in patients with long-standing diabetes [37, 38].

Hyperlipidemia is a well-established modifiable risk factor for CVD, with a direct relationship between low-density lipoprotein (LDL) cholesterol and ASCVD events. Studies have shown that lowering LDL is associated with decreased risk for CVD in both primary and secondary prevention populations which have included women [39]. The INTERHEART trial was a large case control study that sought to quantify the risk of various modifiable risk factors for CVD. Smoking and an abnormal lipid profile (defined as an elevated ApoB/ApoA1 ratio) were the two strongest risk factors for myocardial infarction, with abnormal lipid profiles being the highest of all the risk factors studied [40]. The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol recommends initiation of statins in both women and men with an LDL-C $>$190 mg/dL or an estimated 10-year ASCVD risk of $\ge$7.5% based on the pooled cohort equation risk calculator, which incorporates sex in the calculation [41]. Statin therapy has similar benefits for both women and men in CVD risk reduction, although elderly women are 20% less likely than men to use statins, which may be due to either under prescription or to the higher prevalence of statin-associated myalgias [42, 43, 44].

Cholesterol levels may fluctuate throughout a woman’s life-span, from young adult to pregnancy to the transition to menopause, and treatment should be tailored accordingly. Women are at increased risk of hyperlipidemia, with the postmenopause period being a particularly vulnerable time [45]. Following menopause, women have higher total cholesterol, triglycerides, and LDL, and reduced HDL, which places them at higher risk for CVD [46]. High non-HDL-C and triglyceride levels are more important CVD risk factors in women than men, especially women with diabetes [47, 48].

An elevated lipoprotein(a) level is considered a risk factor that is pro-thrombotic, pro-inflammatory, and pro-atherogenic in both men and women and is associated with a higher risk of CVD events [39]. In the Multi-Ethnic Study of Atherosclerosis (MESA), Lp(a) was associated with increased CVD risk when there was evidence of systemic inflammation as determined by higher C-reactive protein levels ($\ge$2 mg/L) [49]. A randomized, placebo-controlled trial of the impact of lowering Lp(a) on major CVD events is currently ongoing (NCT04023552) [50]. While there are no pharmacologic agents available for routine clinical use to lower Lp(a) levels, small interfering RNA (siRNA) agents that directly inhibit Lp(a) messenger RNA translation in the liver are promising [51]. A review of the management of blood cholesterol throughout a woman’s life cycle, ranging from pre-pregnancy, pregnancy, pre- and perimenopause, postmenopause, and at older ages has recently been published [52]. Table 2 (Ref. [39, 53]) summarizes the current recommendations for the use of therapies such as statins and aspirin for primary and secondary prevention of CVD in women.

Cigarette smoking is the leading behavioral contributor for CVD mortality, with an estimated 30.8 million adults in the United States currently smoking cigarettes [54]. It is associated with multiple forms of CVD, including coronary heart disease, cerebrovascular disease, and peripheral arterial disease [55]. While men are more likely to smoke cigarettes (14.1% vs. 11%), women are disproportionately affected by the risk of CVD [54, 56]. The surgeon general in a weekly morbidity and mortality report in 2002 wrote, “Like their male counterparts who smoke, women smokers are at increased risk of cancer, cardiovascular disease, and pulmonary disease, but women also experience unique risks related to menstrual and reproductive function…it is tragic that an entirely preventable factor continues to claim so many women’s lives” [57]. Huxley et al. [56] conducted a meta-analysis of cohort studies that included 2.4 million individuals and found that compared to non-smokers, women who smoke have a 25% greater relative risk of coronary heart disease than male smokers, after adjusting for other risk factors. All patients should be asked about tobacco use at each office visit; and smokers should be advised to quit and given the tools to do so [58]. Furthermore, AHA/ACCF guidelines also recommend that patients should be advised to avoid environmental tobacco exposure [59].

Electronic cigarettes (e-cigarettes) have been growing in popularity since their introduction in 2007 and contain hazardous compounds [60]. One study found that within one month of switching from tobacco smoking to e-cigarettes, endothelial function assessed by flow mediated dilation (FMD) and vascular stiffness (measured by pulse wave velocity) improved in both men and women, but women had more improvement compared to men [61]. However, other studies have found impaired vascular function with both tobacco cigarettes and e-cigarettes [60]. In a retrospective study of 96,000 participants, those who smoked e-cigarettes were more likely to have myocardial infarction (odds ratio: 1.56) and stroke (odds ratio: 1.3) compared to non-e-cigarette users [62]. Whether e-cigarettes pose a relatively higher risk in women compared to men has not been studied. In a study with over 400 pregnant women, 6.5% were using e-cigarettes during pregnancy and 65% stated that e-cigarettes were safer than tobacco cigarettes. Future studies are needed to address the safety of e-cigarettes on women and fetuses [63].

An elevated body mass index (BMI) is associated with increased CVD risk in both women and men, but there are important sex differences in fat distribution (visceral vs. subcutaneous) [64]. Women predominantly accumulate subcutaneous fat, while men accumulate more visceral fat. However, with menopause, women have increased visceral fat compared to premenopausal women of similar ages, which contributes to insulin resistance and inflammation [65]. Cardiometabolic biomarkers such as serum adiponectin levels also predict CVD risk and mortality in both men and women [66, 67]. Several CVD risk factors are increased in patients with greater adiposity and obesity. For example, HTN is associated with overweight (OR = 2.1) and obesity (OR = 5.2) in women, and diabetes is associated with abdominal obesity (OR = 3.9) in women [68]. Weight reduction is associated with improvements in cholesterol levels, lower blood pressure, and a lower risk of developing type 2 diabetes [69]. Overweight and obese individuals and women with waist circumference of $>$35 inches (88 cm) should be counseled regarding their elevated CVD risk and referred for nutrition counseling as well as prescribed a diet that leads to a 500–750 kcal/day energy deficit [70]. Given the importance of weight management in CVD, strategies such as bariatric surgery should be considered in women with a BMI $\ge$40 or in those with BMI $\ge$35 with comorbid conditions related to obesity, and has been shown to be effective in improving diabetes and other comorbidities [70]. Glucagon-like peptide (GLP-1) agents are a novel class of agents that are associated with weight reduction, decreased insulin resistance, anti-inflammatory effects, and CVD benefits [71].

Physical activity is one of the most important modifiable risk factors for CVD. In one study, the risk of heart disease with physical inactivity was higher compared to other traditional CVD risk factors [72]. The AHA defines adequate physical activity as 150 minutes/week of moderate intensity or 75 minutes/week of vigorous intensity exercise. Physical activity is also part of the AHA’s Life’s Simple 7, created in 2010, which outlines and defines modifiable risk factors that contribute to cardiovascular health [73]. Physical activity levels are lower among women compared to men, especially in AA and Hispanic adults [13]. Women undergo several events throughout their lives that reduce their amount of physical activity compared to men, including pregnancy and parenting [74]. A recent study analyzing the lifetime risk of coronary heart disease based on genetic factors and/or lifestyle modifications (defined in accordance with AHA’s Life’s Simple 7) of nearly 10,000 participants found that lifestyle factors affect overall freedom from coronary heart disease more than genetic factors [75]. Lifestyle factors also have a greater effect on women than men for future CVD events [75]. In a Swedish cohort study, total physical activity time was inversely associated with a risk of myocardial infarction only in women [76]. There may be a dose-dependent risk of CVD in older women ($\ge$63 years old) based on the degree of sedentary lifestyle [77]. Overall, these recent findings further emphasize the importance of physical activity counseling for women regarding their cardiovascular health, especially with aging and through key transition periods in their lives.

Exercise training leads to direct improvements in vascular function, diastolic function, and beneficially alters autonomic tone [78, 79, 80, 81, 82, 83, 84]. In a meta-analysis of 48 randomized trials of cardiac rehabilitation (CR) vs. usual care in ischemic heart disease patients, CR was associated with reduced cardiac mortality (OR = 0.74; 95% CI: 0.61 to 0.96) and all-cause mortality (odds ratio = 0.80; 95% CI: 0.68 to 0.93) [85]. Despite its beneficial effects on morbidity, mortality, functional capacity, and quality of life, CR is unfortunately grossly underutilized in women [86, 87, 88]. A comprehensive cardiac rehabilitation program includes not only aerobic and strength training exercises, but also nutrition counseling, education on tobacco cessation strategies, and psychological evaluation [89].

Eliciting a family history of CVD is important, as this risk factor increases CVD risk. A family history of premature CVD in a first-degree relative (defined as 55 years in men and 65 years in women) is considered a risk enhancing factor, although it is not incorporated in the ACC/AHA Atherosclerotic CVD Risk Estimator [10, 90]. In a large study of patients with acute myocardial infarction, a family history of premature coronary heart disease was an independent predictor of major adverse events and cardiac death, especially in women compared to men [91]. In a study combining cohorts from the Physician’s Health Study (n = 22,071 men) and Women’s Health Study (n = 39,876 women), a history of a maternal MI was associated with increased CVD risk in both sons and daughters. However, a history of paternal MI conferred increased risk for sons, but only premature paternal MI (50 years) conferred increased risk for daughters [92]. In the INTERHEART study, both a paternal and maternal history of MI (defined as having MI at age 50 years) was associated with an increased risk for an MI. The odds ratio for an MI with a paternal history of MI was 1.84 (95% CI: 1.69 to 2.0) vs. 1.72 for a maternal history (95% CI: 1.56 to 1.91) (p = 0.692 for heterogeneity) [93].

Hypertensive disorders of pregnancy are a major cause of maternal morbidity and mortality [94]. Women with pre-eclampsia have not only an increased risk but also an earlier onset of CVD risk factors including HTN, diabetes, and hyperlipidemia [95]. A 2021 Swedish cohort study with over 2 million women and 4 million pregnancies tracked CVD after pre-eclampsia pregnancy complications. CVD mortality rates were higher among those with pre-eclampsia or eclampsia at a hazard ratio (HR) of 2.10, which was the third highest predictor, after stillbirth (3.14) and gestational diabetes (3.03) [96]. The elevated rate of CVD mortality for women with a history of pre-eclampsia was especially pronounced in the 4th post-partum decade [97]. In addition, other adverse pregnancy outcomes (APOs) such as gestational diabetes, preterm birth (37 weeks gestational age), and small for gestational age were also predictive of future CVD compared to women who did not experience APOs. A large systematic meta-analysis of over 300,000 women with a history of preterm delivery found a 1.4- to 2-fold increase for the risk of future maternal CVD (RR: 1.43), CVD death (1.78), coronary heart disease (1.20), and stroke (1.65), with the highest risks when preterm deliveries occurred 32 weeks of gestation or when medically indicated [95, 98]. These risks were higher in those women who had a greater number of preterm births [98]. Of note, excessive gestational weight gain or persistent weight gain post pregnancy also contributes to risk factors such as HTN and increases future CVD risk [99, 100, 101, 102].

Though the pathogenesis is under active investigation, there appears to be an element of chronic inflammation after a complicated pregnancy, resulting in a long-term increase in CVD risk factors [103, 104]. Although pregnancy complications are established CVD risk predictors, knowledge gaps remain as to how these factors should be incorporated to inform decision-making regarding CVD preventive strategies. Women who have experienced an APO should be routinely screened for CVD risk factors, including HTN, diabetes, hyperlipidemia, smoking cessation, and obesity, with counseling and pharmacotherapy when appropriate. It is recommended that women with adverse pregnancy outcomes undergo CVD risk screening within 3 months post-partum [9].

Atherosclerosis is a pathologic, inflammatory process in the vascular wall that is triggered by risk factors such as diabetes, dyslipidemia, and smoking, but also may accelerate due to immune dysregulation from chronic infections such as human immunodeficiency virus (HIV) [125, 126, 127, 128, 129, 130]. Sex hormones play an important role in adaptive and innate immune responses and systemic inflammation in women. Moran et al. [130] published a review of mechanisms involving immune dysregulation which contribute to inflammation and increase the risk of CVD in women.

C-Reactive Protein (CRP) is a marker of inflammation and has been shown to be a risk factor for cardiovascular events. It is incorporated in the Reynolds Risk Score for improved risk prediction in women [131]. Inflammatory cytokines are thought to stimulate the liver to produce CRP, which is an acute phase reactant [132]. Elevated high sensitivity CRP (hsCRP) levels are predictive of CVD events [133, 134]. Statins, a mainstay of CVD management and prevention, have been shown to reduce hsCRP levels [135, 136]. Thus the benefit of statins in reducing cardiovascular risk is thought to be in part due to their anti-inflammatory properties. Modulating the inflammatory response to reduce CVD risk has been studied in several clinical trials using agents such as canakinumab and colchicine [137, 138, 139]. The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) demonstrated that in patients with a history of an MI and high sensitively CRP $>$2 mg/mL, targeting interleukin-1$\beta$ (an inflammatory signaling molecule) reduces CVD events compared to placebo [140]. Canakinumab at a dose of 150 mg every 3 months led to significantly lower rates of recurrent CVD events, independent of lipid lowering, suggesting that targeting inflammation plays a role in CVD reduction [140]. Tumor necrosis factor-alpha (TNF-$\alpha$) therapy, in conditions such as rheumatoid arthritis, may also be associated with improved outcomes in CVD [141].

In addition to the above risk factors, several studies have shown that psychological risk factors such as anxiety, work and marital stress, depression, low socioeconomic status and loneliness, are associated with CVD [147, 148, 149, 150, 151, 152, 153, 154]. In the Stockholm Female Coronary Risk (FemCorRisk) study of community women with CAD, marital stress predicted a poor prognosis with three times the increased risk of coronary events after controlling for other risk factors [155]. In 300 young and middle-aged patients (ages 18 to 60 years) with a history of a recent MI, chronic stress burden with self-reported early-life trauma was also found to be an independent risk factor for adverse CVD outcomes in both men and women (66% AA and 50% women) [156]. In another large, prospective study of 23,196 men and women (ages 20 to 54 years), childhood adversities were more powerful predictors of CVD in women compared to men [157].

While conditions such as post-traumatic stress disorder are being increasingly recognized as risk factors for CVD [158], the link between depression and its impact on heart disease is already well established [159]. Depression is associated with autonomic nervous system dysregulation as well as inflammation [152, 160]. Patients who are depressed are also less likely to make heart-healthy choices, have uncontrolled cardiac risk factors, lower medication compliance, and medical follow-up. In the Women’s Health Initiative (WHI), depression was an independent predictor of cardiovascular death [161]; similarly, in the Nurses’ Health Study, depression was associated with an increased incidence of adverse cardiac events [162].

Several studies have looked at how neurobiological mechanisms and emotions may influence stress physiology and lead to heart disease [154, 163]. In patients with stable CAD, even transient endothelial dysfunction, measured by flow-mediated dilation of the brachial artery during mental stress tasks, was a prognostic marker associated with adverse outcomes (composite endpoint of CV death, MI, revascularization, and health failure hospitalization) after adjusting for medical history and sociodemographic risk factors [164]. Women, in particular, seem to be more at risk for adverse consequences of mental stress. For example, young women with a history of an MI have more ischemia with mental stress compared to young men with an MI [165, 166]. Among 918 patients with stable CAD, those with mental stress ischemia (16% of the cohort) had increased cardiovascular death or non-fatal MI compared to those with no mental-stress ischemia at a median of 5 years of follow-up. Furthermore, compared to young men, young women with CAD had a greater inflammatory response with interleukin-6 to mental stress [167]. Sex-differences in vascular reactivity to mental stress have also been documented, with women having more microvascular vasoconstriction in response to laboratory-induced mental stress. Similarly, post-menopausal women are more susceptible to takotsubo syndrome after a significant emotional or physical stressor [168].

While anti-neoplastic therapy is necessary to combat cancer, some types are associated with cardio-toxic effects and increase CVD risk. Over the past decade the field of cardio-oncology has emerged to address consequences of cancer therapy not only in the short-term, but also long-term in cancer survivors. A consensus statement defining cardiovascular toxicities from cancer was recently published by the International Cardio-Oncology Society (IC-OS) [169]. Anthracycline-based therapy has been known to be associated with cardiomyopathy, and newer agents such as tyrosine kinase inhibitors that target vascular endothelial growth factor (VEGF) (e.g., bevacizumab, sunitinib, sorafenib); are associated with HTN and left ventricular dysfunction (Fig. 2) [169, 170]. Baseline cardiovascular risk assessment in patients who are undergoing chemotherapy can be helpful; since as the number of CVD risk factors increase, the risk of cardiotoxicity also increases [171]. A comprehensive position statement on risk assessment tools to address baseline risk in patients who are starting chemotherapy has been recently published by the European Society of Cardiology and ICOS [171]. While a comprehensive review of cardiotoxic effects related to specific cancers and chemotherapy is beyond the scope of this manuscript, we have focused on breast cancer since it is the most common cancer in women.

Fig. 2.

Cardiotoxic effects of chemotherapy. Chemotherapeutic agents are associated with various cardiotoxic effects. Timely cardiovascular assessment prior to chemotherapy initiation, and close monitoring, as well as surveillance post-therapy, are recommended. VEGF, Vascular endothelial growth factor.

While advances in early detection and targeted treatment have led to declining death rates in breast cancer, some therapies have been associated with significant adverse cardiac events [172, 173, 174, 175, 176]. There are an estimated 3.8 million breast cancer survivors in the U.S. [177]. Adverse events, including myocardial ischemia, heart failure, venous thromboembolism, and bradycardia may result from breast cancer treatment, among which anthracyclines carry the highest risk of cardiotoxicity [178]. Following long-term therapy, a large percentage of patients exposed to anthracycline-based therapy develop abnormalities in cardiac structure and function, placing them at five-times the risk of heart failure compared to patients treated with non-anthracycline-containing chemotherapy [173]. Women who have a higher baseline burden of CVD risk factors are particularly vulnerable to adverse consequences following cancer chemotherapy [179]. The cardiotoxic effects of doxorubicin are dose-dependent, with heart failure noted in 26% of patients given the maximum lifetime cumulative dose of 550 mg/m${}^2$ [178]. The myocardial cellular damage that leads to direct myocardial injury and myocyte apoptosis is thought to be irreversible (Type I cardiotoxicity). Therefore, anthracycline-based agents are associated with significant mortality and morbidity [180, 181]. Other groups of chemotherapy agents (e.g., trastuzumab) generally do not cause direct myocellular damage and are associated with reversible left ventricular dysfunction (Type II cardiotoxicity) [182]. A retrospective cohort study of 12,500 women with breast cancer demonstrated a hazard ratio (HR) of 1.4 in patients on anthracycline alone, a HR of 4.1 in patients treated with trastuzumab alone, and a HR of 7.19 in those treated with both agents as compared to patients who received no chemotherapy, indicating a higher risk when anthracycline and trastuzumab are combined [183]. Other treatments associated with LV dysfunction and heart failure include alkylating agents (cyclophosphamides), anti-microtubule agents (taxanes), and monoclonal antibodies (trastuzumab). Cardiac ischemia has been noted in approximately 5% of patients treated with taxanes [184]. Alkylating agents can cause mild cardiac arrhythmias [185]. Anti-microtubule agents may cause myocardial ischemia, heart failure, ventricular tachycardia, and atrioventricular block [186]. A recent meta-analysis showed that several medications, including statins, were effective in reducing the risk of cardiac injury in cancer patients [173]. Cardiovascular toxicity resulting from radiotherapy, predominately for left-sided breast cancer, has been well-documented, especially among women receiving whole heart doses of $\ge$5 gray, as was the previous standard of care [187]. Radiation-related injury may include structural damage to the heart, such as fibrosis, pericardial adhesions, microvascular damage and valvular stenosis, as well as damage to the coronary arteries [188].

Chest wall or mediastinal radiation for treatment of malignancies such as Hodgkin’s lymphoma and breast cancer is associated with coronary atherosclerosis, as well as pericardial and valvular disease. The risk of radiation-induced heart disease increases in the presence of risk factors. An elevated risk for CVD starts within the 5 years of radiation exposure, and the rate of events increases by 7.4% per gray of radiation [189]. Left-breast radiation doses to the heart are higher than right-sided breast radiation and is associated with atherosclerosis in both the left and right coronary arteries [190]. It is important to continue to screen for CVD risk factors and atherosclerosis to guide the management in patients exposed to cardio-toxic chemotherapy or radiation therapy.

There is a substantial lack of awareness, especially among young and racial/ethnic minority women, that CVD is a major health threat in women, and targeted educational efforts are needed [201]. Multi-specialty and team-based care to improve CVD risk factor control is needed to make progress in the battle against CVD in women [202]. Moreover, an improved understanding of how to practically incorporate socio-cultural factors and social determinants to guide care in women is essential [1, 203]. Several questions regarding optimal risk factor assessment and deployment of pharmacotherapy remain: Does early treatment of cardiac risk factors in women with adverse pregnancy outcomes lead to a significant reduction in mortality? Should preventive strategies such as statins and aspirin be recommended to all patients with underlying chronic autoimmune inflammatory disorders? Should young women with autoimmune inflammatory disorders or adverse pregnancy outcomes undergo coronary artery calcium scoring to help guide primary prevention, and if so, starting at what age? Does early initiation of menopause hormone therapy, especially transdermal formulations, during the transition to menopause in younger women under the age of 60, attenuate the cardiometabolic and hypertensive risk associated with declining estrogen levels?

Adverse drug reactions (ADRs) can range from mild, simple rash, to severe and life-threatening conditions such as angioedema. There has been a historic lack of comparisons of the rate of adverse reactions between men and women in clinical trials [204]. There are sex-specific differences in the incidence of drug reactions among common cardiovascular medications, with women experiencing adverse events more often than men [205]. For example, an increased incidence of ADRs has been observed with ACE-I (enalapril) (odds ratio 1.30) and particularly a higher risk of cough in women compared to men (odds ratio: 2.38) [206]. In a meta-analysis comparing the effects of statins on cardiovascular outcomes, no differences in adverse drug reactions were found in women compared to men; however, data for myopathy and new-onset diabetes were limited [207].

What are the main barriers that prevent optimal CVD risk assessment care in young women and what system level changes can be optimized to reduce the sex-based disparities in CVD care? Questions related to pathobiological differences in CVD in women vs. men should also continue to be investigated [208]. Improved education, screening, identification, and treatment (pharmacologic and lifestyle-based approaches) of CVD risk factors in women require engagement across all levels and a systems-based approach (Fig. 3) [209].

Fig. 3.

Pillars for integrated cardiovascular risk factor care in women. Optimizing and improving CVD care for women requires efforts at all levels. SDoH, Social Determinants of Health. Figure created using https://Biorender.com.