Discussion on LDL-C Reduction and Cardiovascular Risk in a High-Risk Patient

The following question refers to Section 3.2 of the 2021 ESC CV Prevention Guidelines. The question is asked by student Dr. Hirsh Elhence, answered first by Mayo Clinic Fellow Dr. Teodora Donisan, and then by expert faculty Dr. Eugene Yang. Dr. Yang is professor of medicine of the University of Washington where he is medical director of the Eastside Specialty Center and the co-Director of the Cardiovascular Wellness and Prevention Program. Dr. Yang is former Governor of the ACC Washington Chapter and current chair of the ACC Prevention of CVD Section. The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Question #13 You are seeing a 45-year-old woman with a past medical history of hypertension, overweight status, hyperlipidemia, and active tobacco use disorder. Her BMI is 27 kg/m2, BP is 150/75, HbA1C is 5.8%, total cholesterol is 234 mg/dL, HDL is 59 mg/dL, and LDL is 155 mg/dL. She is from Romania, a country with very high CVD risk. Which of the following statements is CORRECT? A. LDL-C needs to be decreased by at least 50%, as small absolute LDL-C reductions would not provide clinical benefit B. Hypertension is not an important CVD risk factor in our patient, as she is young. C. Prediabetes is not a significant CV risk factor for our patient, as she is not yet diabetic. D. Smoking confers a higher CVD risk for women than for men. E. Her weight does not increase her CVD risk, as she is overweight rather than obese Answer #13 The correct answer is D – Smoking confers a higher CVD risk for women than for men. Prolonged smoking increases the CVD risk more in women than in men. Our patient is 45 years old. CVD risk in smokers < 50 years-old is 5x higher than in non-smokers. Of note, smoking is responsible for 50% of all avoidable deaths in smokers and a lifetime smoker will lose 10 years of life, on average. Secondhand smoke and smokeless tobacco can also increase the CVD risk. Option A is incorrect. The SCORE2 risk chart for populations at very high CVD risk places her at a 14% (very high) 10-year risk for myocardial infarction, stroke, or cardiovascular death. She would derive benefit even from incremental reductions in LDL-C values. The absolute benefit of lowering LDL-C depends on both the absolute risk of ASCVD and the absolute reduction in LDL-C, so even a small absolute reduction in LDL-C may be beneficial in high- or very-high-risk patients. Furthermore, the reduction in CVD risk is proportional to the decrease in LDL-C, irrespective of the medications used to achieve such change. This remains true even when lowering LDL-C values to < 55 mg/dl. Option B is incorrect. Hypertension is a major cause of CVD regardless of age, and the risk of death from either CAD or stroke increases linearly from BP levels as low as 90 mmHg systolic and 75 mmHg diastolic upwards. Particularly relevant for our patient, lifetime BP evolution differs in women compared to men, potentially resulting in an increased CVD risk at lower BP thresholds. Option C is incorrect. Type 1 DM, type 2 DM, and prediabetes are all independent risk factors for ASCVD. Of note, it would be important to address this risk factor with our patient, as women who develop type 2 diabetes have a particularly high risk for stroke. Option E is incorrect. All-cause mortality is lowest at a BMI on 20-25 kg/m2 in apparently healthy patients. Even overweight patients are at increased CVD risk. There is a linear relationship between BMI and mortality in non-smokers and a J-shaped relationship in ever-smokers. In patients with heart failure, a lower mortality risk has been observed with higher BMI – the “obesity paradox.” It would be important to evaluate the waist circumference in our patient, as both BMI and waist circumference are associated with ASCVD risk.