Premature atherosclerotic cardiovascular disease in a young woman of childbearing age: Cardiovascular and obstetric implications

Abbreviations

LDL-C

Low-density lipoprotein cholesterol

Lp(a)

lipoprotein(a)

NSTEMI

non-ST-elevation myocardial infarction

ASCVD

Atherosclerotic cardiovascular disease

HDL-C

High-density lipoprotein cholesterol

MI

myocardial infarction

PCSK9

proprotein convertase subtilisin/kexin type 9.

1. Introduction

The rising burden of cardiovascular disease and cardiometabolic disorders in younger populations presents a unique clinical challenge in both diagnosis and management [1] This trend is reflected in global prevalence data spanning 1990 to 2019, which documented substantial increases in ischemic heart disease, ischemic stroke and peripheral artery disease among adults aged 20 to 54 years, rising by 20.55 %, 11.50 % and 7.38 % respectively [2] Among adults aged 18 to 44 years in the United States, the prevalence of diabetes and dyslipidemia, two cardinal components of cardiometabolic disease, was 4.3 % and 37.3 %, respectively, with 45.2 % of the group having two or more lifestyle-related risk factors [3] Evidence from the YOUNG-MI registry further illustrates that young adults are largely undertreated for cardiometabolic risk before experiencing a serious cardiac event [4] Despite this concerning trend, women consistently receive less aggressive therapeutic intervention relative to their male counterparts and this disparity carries meaningful clinical consequences.

Non-ST-elevation myocardial infarction (NSTEMI) occurring in patients under 40 years of age is particularly concerning, as it frequently reflects an aggressive atherogenic profile driven by multiple concurrent metabolic abnormalities. In women of reproductive age, cardiovascular risk assessment takes on additional complexity, given that many of the same metabolic derangements that promote atherosclerosis, including dyslipidemia, insulin resistance, and chronic inflammatory states, can also adversely affect pregnancy outcomes [5] Emerging evidence links severe dyslipidemia and metabolic syndrome to serious obstetric complications such as recurrent pregnancy loss, preeclampsia, and placental insufficiency through shared pathophysiologic mechanisms including endothelial dysfunction, oxidative stress, and prothrombotic states [6] We present the case of a young woman with established atherosclerotic cardiovascular disease, elevated low-density lipoprotein cholesterol (LDL-C), type II diabetes mellitus with poor glycemic control, and elevated lipoprotein(a) [Lp(a)], who conceived unexpectedly and suffered the devastating loss of a triplet pregnancy. This case illuminates the profound complexities inherent in the management of women with pre-existing cardiovascular disease and affirms the importance of multidisciplinary management in this vulnerable population.

2. Clinical case

A 29-year-old Hispanic female G4P0A4 with a medical history significant for hypertension, uncontrolled diabetes mellitus, hyperlipidemia and four first-trimester miscarriages presented to the preventive cardiology clinic for cardiovascular evaluation following a recent hospital admission for non-ST elevation myocardial infarction (NSTEMI).

Two weeks prior to her appointment, she had presented to the hospital with left-sided chest pain that radiated to her left arm. On admission, vital signs were notable for hypertension with a blood pressure of 193/111 mmHg, heart rate of 92 beats per minute, weight of 83.5 kg, height of 165.1 cm, and BMI of 30.6 kg/m². Initial laboratory investigations revealed an elevated troponin level of 401 ng/L, poorly controlled diabetes with a hemoglobin A1c of 13.0 % and dyslipidemia with total cholesterol of 302 mg/dL, high-density lipoprotein cholesterol (HDL-C) of 40 mg/dL, and LDL-C of 158 mg/dL. Notably, her lipoprotein(a) was elevated at 223 nmol/L. She had no prior history of alcohol or illicit drug use and had no known family history of coronary artery disease. She was diagnosed with NSTEMI and underwent left heart catheterization, which revealed diffuse multivessel coronary artery disease (Fig. 1). Angiographic findings demonstrated diffuse disease in the left anterior descending artery (LAD), subtotal occlusion of the first diagonal branch of the LAD (D1) and chronic total occlusion in the left circumflex artery (LCX). Although she had been receiving treatment prior to her presentation with acute coronary syndrome, it became apparent that she lacked awareness of the severity of her diabetes and was intermittently non-adherent to her medications. Given the extensive nature of her coronary artery disease, cardiothoracic surgery was consulted for evaluation for coronary artery bypass grafting. Following multidisciplinary discussion, surgical revascularization was deemed inappropriate due to the presence of diffuse diabetic vasculopathy and poor distal targets. The patient was initiated on optimized medical therapy and referred to preventive cardiology for continued management.

Fig. 1.

Left heart catheterization showing diffuse disease in the left anterior descending artery (LAD), subtotal occlusion of the first diagonal branch of the LAD (D1) and chronic total occlusion in the left circumflex artery (LCX).

In the preventive cardiology clinic, she was evaluated jointly by cardiology and endocrinology and her medical regimen was comprehensively optimized. Her regimen comprised amlodipine 2.5 mg daily, aspirin 81 mg daily, evolocumab 140 mg subcutaneously every two weeks, ezetimibe 10 mg daily, icosapent ethyl 1 g twice daily, metoprolol 25 mg twice daily, rosuvastatin 40 mg daily, and tirzepatide which was gradually uptitrated to a maintenance dose of 15 mg weekly. Following thorough medication counseling, the patient demonstrated commendable adherence to her prescribed regimen and progressively achieved an improved functional capacity, tolerating physical activity without chest pain or other limiting symptoms. Given that she was a woman of childbearing age, appropriate preconception counseling was thoughtfully incorporated into her clinical care as well. She was advised of the contraindications of several agents within her medical regimen during pregnancy and strongly encouraged to use reliable contraception.

Following one year of intensive medical therapy, significant improvements were observed in her biometrics and cardiometabolic parameters. Blood pressure normalized to 116/70 mmHg, resting heart rate to 60 beats per minute, and body weight decreased to 81.4 kg, corresponding to a body mass index of 29.85 kg/m². Laboratory investigations showed marked improvement with hemoglobin A1c declining to 6.6 %, total cholesterol to 98 mg/dL, HDL-C rising to 46 mg/dL, and LDL-C decreasing to 44 mg/dL. She engaged closely with a registered dietitian and adapted meaningful lifestyle modifications, incorporating a structured exercise program that included a combination of cardiovascular and strength training into her routine. Eighteen months following her index acute coronary syndrome, the patient presented to the cardiology clinic at 13 weeks of gestation with an unanticipated triplet pregnancy. She was promptly referred to obstetrics and gynecology and maternal-fetal medicine for the establishment of specialized prenatal care.

Her cardiovascular medications were carefully reviewed and adjusted in accordance with pregnancy safety profiles. Amlodipine was discontinued and replaced with labetalol for blood pressure management, while lipid lowering therapy was suspended, given its contraindication in pregnancy. Throughout this period, her care was coordinated by a comprehensive multidisciplinary team including preventive cardiology, endocrinology, obstetrics, and maternal-fetal medicine. Unfortunately, she experienced fetal losses of triplets A and B at 18 weeks of gestation, followed one week later by spontaneous abortion of triplet C attributed to cervical incompetence.

3. Discussion

Cardiovascular disease is increasingly recognized as a leading cause of mortality among women, with recent data demonstrating a rising incidence, particularly among younger women [7] Maternal cardiovascular disease has now emerged as the foremost cause of non-obstetric mortality during pregnancy [8,9] Traditionally, coronary artery disease manifests later in women than in men, however, the presence of multiple cardiovascular risk factors can accelerate the process of atherogenesis significantly. Despite available screening, many young adults remain unaware of underlying cardiometabolic risk factors such as hypertension, diabetes, and high cholesterol and are consequently undertreated or untreated [[10], [11], [12], [13]] Suboptimal management of these disease conditions, particularly in young women, can contribute to increased cardiovascular risk and cause cardiometabolic dysregulation, that ultimately manifests as adverse pregnancy outcomes. In the present case, the combination of uncontrolled diabetes mellitus, severe hypertension, dyslipidemia, obesity, and markedly elevated lipoprotein(a) culminated in accelerated atherosclerosis at an unusually early age.

Through the implementation of a structured multidisciplinary care model and comprehensive patient education, intensive medical therapy yielded remarkable improvements in her cardiometabolic profile over the course of one year, highlighting the transformative potential of aggressive early risk factor modification. Many younger patients are undertreated for their cardiometabolic risk factors, in part due to the prevailing misconception that they are low risk at a young age. Yet when cardiometabolic risk factors are present early in life, they compound over time, leading these patients to an unprecedented increase in lifetime cardiovascular risk [14] While the index patient’s presentation of acute coronary syndrome represents an extreme manifestation due to her young age, it is well established that the overwhelming majority of cardiovascular disease is preventable when risk factors are identified and addressed in a timely and systematic fashion.

Beyond the management of cardiometabolic risk factors, pregnancy in the setting of pre-existing cardiovascular disease substantially increases the risk of complications for both mother and fetus. The physiologic changes that normally occur during pregnancy which include: increased myocardial contractility, a 50 % increase in cardiac output, ventricular hypertrophy, and an expansion of maternal blood volume by about 1.5 liters, places a burden on the maternal cardiovascular system and can exacerbate underlying disease [15] Furthermore, the limitation of medical therapy that can be administered during pregnancy due to the safety profiles of many medications, leaves many women particularly those with established disease, vulnerable and disproportionately exposed to risk. Leveraging a multidisciplinary care approach across subspecialties such as cardiology, lipidology, obstetrics and gynecology, maternal-fetal medicine, and endocrinology is expedient in crafting individualized management strategies to optimize these high-risk patients.

There is a bidirectional relationship that exists between cardiometabolic disease and recurrent miscarriage. It is also worth considering that our patient’s medical history is significant for four prior recurrent first-trimester miscarriages. Although formal evaluation was not undertaken at the time, it may be hypothesized that her recurrent miscarriages could be attributed to undiagnosed and inadequately treated underlying cardiometabolic abnormalities [12,13] While her most recent pregnancy ended in fetal losses, it is important to note that this pregnancy occurred after significant improvement in her cardiometabolic status and despite the tragic outcome, represented the longest gestational period the patient had achieved to date. The broader implications can be further put in perspective by a systematic review on 116 pregnant women with pre-existing ischemic heart disease, which documented obstetric complications in 58 % of pregnancies, and fetal/neonatal complications in 42 %. The study also shows that these women have a high risk of ischemic cardiovascular complications, including a 2 % maternal mortality [16] The findings in this case are hypothesis-generating for the profound implications of cardiometabolic risk factors among women of childbearing age.

Her earlier suboptimal adherence with prescribed medications and other noticeable gaps in her care preceding her cardiovascular event are suspected to have contributed to the subsequent unfavorable clinical outcome, though the exact etiology of the fetal losses remains undetermined. It is plausible that some of the losses could be a direct result of the pathophysiological changes already set in motion by her longstanding and inadequately managed cardiometabolic disease. Women and young women in particular, despite frequently meeting the criteria for lipid-lowering therapy, are less likely to be initiated on treatment and less likely to attain recommended therapeutic targets for LDL-C [12] This therapeutic gap is further compounded by the considerable burden of hypertensive disorders of pregnancy which complicate 13–15 % of all pregnancies in the United States [17] Given the rise in prevalence of cardiometabolic disease, particularly among young individuals, and the frequency with which adverse pregnancy outcomes occur, stronger consideration should be given to screening for cardiometabolic risk factors such as hypertension, hyperlipidemia [including elevated Lp(a)], and diabetes mellitus at a preconception visit. Women of reproductive age with cardiovascular disease or significant cardiometabolic risk factors require dedicated, specialized preconception counseling tailored to mitigate risk and optimize both maternal and fetal outcomes.

4. Conclusion

This case highlights several important clinical considerations regarding premature coronary artery disease in a young woman, the inherent challenges of cardiovascular risk factor optimization in women of reproductive age, and the complex interplay between cardiovascular disease, cardiometabolic risk factors, and adverse pregnancy outcomes. Further studies are needed to delineate optimal management strategies for women with pre-existing cardiovascular disease who desire pregnancy, a population whose needs remain insufficiently addressed in the current literature. The successful management of premature coronary artery disease in young women demands a comprehensive and individualized approach, integrating early screening, intensive risk factor modification, coordinated multidisciplinary care and the use of targeted therapies, to improve cardiovascular health and preserve reproductive outcomes.

Funding and disclosures

None.

Author statement

All authors have approved this work. There are no relevant COI or financial disclosures for any of the authors.

CRediT authorship contribution statement

Onyinye Ugoala: Writing – original draft, Writing – review & editing. Neeka Tavanaei: Writing – original draft, Writing – review & editing. Susmitha Potti: Writing – original draft, Writing – review & editing. Anandita Kulkarni: Conceptualization, Writing – original draft, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.