CardioNerds Rounds Co-Chairs, Dr. Karan Desai and Dr. Natalie Stokes and CardioNerds Academy Fellow, Dr. Najah Khan, join Dr. Martha Gulati – President-Elect of the American Society for Preventive Cardiology (ASPC) and prior Chief of Cardiology and Professor of Medicine at the University of Arizona – to discuss challenging cases in cardiac prevention. As an author on numerous papers regarding cardiac prevention and women’s health, Dr. Gulati provides many prevention pearls to help guide patient care. Come round with us today by listening to the episodes now and joining future sessions of #CardsRounds!

This episode is supported with unrestricted funding from Zoll LifeVest. A special thank you to Mitzy Applegate and Ivan Chevere for their production skills that help make CardioNerds Rounds such an amazing success. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. Case details are altered to protect patient health information. CardioNerds Rounds is co-chaired by Dr. Karan Desai and Dr. Natalie Stokes. 

Speaker disclosures: None

Cases discussed and Show Notes • References • Production Team

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Case #1 Synopsis:

A 55-year-old South Asian woman presents to prevention clinic for an evaluation of an elevated LDL-C. Her prior history includes hyperlipidemia, hypertension, obesity, and pre-eclampsia. She was told she had “high cholesterol” a few years prior and would need medication. She started exercising regularly and cut out sweets from her diet. Before clinic, labs showed: Total Cholesterol (mg/dL) of 320, HDL 45, Triglycerides 175, and (directly measured) LCL-C 180. Her Lipoprotein(a) is 90 mg/dL (ULN being ~ 30 mg/dL). Her HbA1C is 5.2% and her 10-year ASCVD Risk (by the Pooled Cohorts Equation) is 5.4%. Her recent CAC score was 110. She prefers not to be on medication and seeks a second opinion.

Takeaways from Case #1

1. As Dr. Gulati notes, in the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, South Asian ethnicity is considered a “risk enhancing factor.” The pooled cohort equations (PCE) may underestimate risk in South Asians. Furthermore, risk varies within different South Asian populations, with the risk for cardiovascular events seemingly higher in those individuals of Bangladeshi versus Pakistani or Indian origin. There are multiple hypotheses for why this may be the case including cultural aspects, such as diet, physical activity, and tobacco use. A better understanding of these factors could inform targeted preventive measures.
2. In the same 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease mentioned above, history of an adverse pregnancy outcome (APO) increases later ASCVD risk (e.g., preeclampsia) and is also included as a “risk-enhancing factor.” Studies have shown that preeclampsia is an independent risk factor for developing early onset coronary artery calcification.
3. Recent data has shown that the risk for developing preeclampsia is not the same across race and ethnicity, with Black women more likely to develop preeclampsia. Black women also had the highest rates of peripartum cardiomyopathy, heart failure, and acute renal failure. After adjustment for socioeconomic factors and co-morbidities, preeclampsia was associated with increased risk of CVD events in all women, the risk was highest among Asian and Pacific Islander women. Listen to Episode #174. Black Maternal Health with Dr. Rachel Bond to learn more about race-based disparities in cardio-obstetric care and outcomes.
4. Our patient thus has multiple risk-enhancing factors to help in shared decision making and personalize her decision for statin use. Another risk-enhancing factor for her is an elevated Lp(a), which is considered elevated when ≥ 50 mg/dL or ≥ 125 nmol/L.
5. One other aspect that Dr. Gulati briefly covered was how CAC score may inform Aspirin use for primary prevention. There continues to be debate over when to prescribe aspirin when there is demonstrable calcium on imaging. In the MESA study, for individuals with CAC ≥ 100, the NNT (for 5 years to prevent an ASCVD event) was a 140 and NNH was 518.

Case #2 Synopsis:

A 58-year-old woman presents to establish care at a general cardiology clinic for shortness of breath. Her history includes hypertension, cutaneous lupus, and ongoing tobacco use. A year ago, she started having nausea, more common with stress or on exertion. She saw her PCP who obtained an EKG and GI evaluation. Endoscopy was unrevealing and EKG showed non-specific ST-T changes inferiorly. She was treated for GERD and then 6 months prior she developed dyspnea on exertion while exercising on her stationary bike after 10 minutes; she previously could go 30 minutes. She suffered a left knee meniscal tear shortly thereafter. She sees a cardiologist and obtains a cardiac PET-Stress which showed a small area of reversible ischemia in the basal to mid inferior wall and borderline reduced coronary flow reserve. Her symptoms continued and she was referred for LHC which showed non-obstructive CAD. No intracoronary physiologic testing was done. She is started on aspirin but still having symptoms. She seeks your opinion on how to prevent cardiovascular events.

 Takeaways Case #2

1. In the VIRGO study, investigators interviewed 2009 women and 976 men aged 18 to 55 years hospitalized for acute myocardial infarction (AMI) at 103 United States hospitals. Approximately 29.5% of women and 22.1% of men sought medical care for similar chest pain symptoms before their hospitalization; however, 53% of women reported that their provider did not think these symptoms were heart-related in comparison with 37% of men (p < 0.001).
2. As Dr. Gulati noted, angiographically obstructive CAD is just the tip of the iceberg when it comes to ischemic heart disease. There are several important phenotypes including diffuse non-obstructive CAD and coronary microvascular dysfunction. Dr. Gulati shared the following image to demonstrate how ischemic heart disease is a unifying term for different syndromes.

Academy Fellow, Dr. Najah Khan, has created the following infographic that provides a distinction between INOCA (ischemia and no obstructive coronary artery disease) and MINOCA (myocardial infarction with non-obstructive coronary arteries).

Case #3 Synopsis:

A 50-year-old man presents to cardiology clinic after a STEMI. His history includes hypertension, diabetes, obesity, and prior tobacco use. Four months ago, the patient suffered an inferior STEMI complicated by VF arrest treated with PCI to the proximal RCA. There was significant residual CAD and tentative plan for staged CABG. The patient was discharged on Aspirin, Prasugrel, Metoprolol Succinate, Lisinopril, Metformin and Atorvastatin. However, he started having muscle aches and so he stopped his Atorvastatin. He sees his PCP and before clinic gets a Lipid Panel (mg/dL) with Total Ch at 230, TG 237, HDL at 36 and LDL-C at 140. The patient starts ezetimibe and then comes to see you a month later to discuss best secondary prevention measures.

Case #3 Takeaways:

1. There are multiple opportunities for secondary prevention following acute coronary syndrome, with many patients undertreated. This includes but not limited to LDL-lowering medications, smoking cessation, cardiac rehabilitation, blood pressure control, diabetes management, weight loss, and targeting non-LDL particles when appropriate.
2. Dr. Gulati points out that we need to make sure we categorize a patient’s risk appropriately, including patients at “very high risk” of ASCVD. This requires multiple ASCVD events (recent ACS, history of MI, history of ischemic stroke, symptomatic PAD) or an ASCVD event with multiple high-risk conditions (e.g., Age ≥ 65, heterozygous familial hypercholesterolemia, history of prior CABG or PCI outside of major ASCVD events, diabetes, hypertension, CKD, current tobacco use, persistently elevated LDL-C despite max statin therapy and ezetimibe, and/or history of congestive heart failure).
3. Patients at very high risk of ASCVD should be on a high intensity statin or maximally tolerated statin (Class I). If PCSK9 inhibitors are considered, it is Class I to add ezetimibe to maximal statin therapy before initiating PCSK9i. If a patient is deemed to be on the maximal LDL-C lowering therapy that s/he is able to tolerate but LDL-C remains ≥ 70 mg/dL or non-HDL-C ≥ 100 mg/dL, adding PCSK9i is reasonable (Class IIa).
4. A take home message from Dr. Gulati is that after more than a quarter century of treating LDL-C, generally the lower we can drive LDL-C levels the better for patient outcomes.

1. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Sep 10;140(11):e596-e646. doi: 10.1161/CIR.0000000000000678. Epub 2019 Mar 17. Erratum in: Circulation. 2019 Sep 10;140(11):e649-e650. Erratum in: Circulation. 2020 Jan 28;141(4):e60. Erratum in: Circulation. 2020 Apr 21;141(16):e774. PMID: 30879355; PMCID: PMC7734661.
2. Benschop L, Brouwers L, Zoet GA, et al. Early Onset of Coronary Artery Calcification in Women With Previous Preeclampsia. Circ Cardiovasc Imaging. 2020 Nov;13(11):e010340. doi: 10.1161/CIRCIMAGING.119.010340. Epub 2020 Nov 16. PMID: 33190533.
3. Cainzos-Achirica M, Miedema MD, McEvoy JW, et al. Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019: The MESA Study (Multi-Ethnic Study of Atherosclerosis). Circulation. 2020 May 12;141(19):1541-1553. doi: 10.1161/CIRCULATIONAHA.119.045010. Epub 2020 Apr 1. PMID: 32233663; PMCID: PMC7217722.
4. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Jun 25;73(24):3168-3209. doi: 10.1016/j.jacc.2018.11.002. Epub 2018 Nov 10. Erratum in: J Am Coll Cardiol. 2019 Jun 25;73(24):3234-3237. PMID: 30423391.
5. Lichtman JH, Leifheit EC, Safdar B, et al. Sex Differences in the Presentation and Perception of Symptoms Among Young Patients With Myocardial Infarction: Evidence from the VIRGO Study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Circulation. 2018 Feb 20;137(8):781-790. doi: 10.1161/CIRCULATIONAHA.117.031650. PMID: 29459463; PMCID: PMC5822747.
6. Minhas AS, Ogunwole SM, Vaught AJ, et al. Racial Disparities in Cardiovascular Complications With Pregnancy-Induced Hypertension in the United States. Hypertension. 2021 Aug;78(2):480-488. doi: 10.1161/HYPERTENSIONAHA.121.17104. Epub 2021 Jun 8. PMID: 34098730; PMCID: PMC8266726.
7. Volgman AS, Palaniappan LS, Aggarwal NT et al. Atherosclerotic Cardiovascular Disease in South Asians in the United States: Epidemiology, Risk Factors, and Treatments: A Scientific Statement From the American Heart Association. Circulation. 2018 Jul 3;138(1):e1-e34. doi: 10.1161/CIR.0000000000000580. Epub 2018 May 24. Erratum in: Circulation. 2018 Jul 31;138(5):e76. PMID: 29794080.