230 ‒ Cardiovascular disease in women: prevention, risk factors, lipids, and more

KEYPOINTS

• 01

  Heart disease mortality in younger women has stopped improving.

  Michos, a Johns Hopkins preventive cardiologist, describes her European Heart Journal analysis of CDC WONDER data on US women under 65 from 1999 to 2019: cancer mortality kept declining, but since about 2010 progress on heart disease stalled and reversed. Worldwide, she cites roughly 18.5–19 million deaths a year from atherosclerotic cardiovascular disease versus about 10–11 million from cancer.

• 02

  Women increasingly don't know heart disease is their top killer.

  In 2009, 65% of women surveyed knew heart disease was the leading cause of death in women; by 2019 only 44% did. Young patients fear breast cancer more, even though heart disease mortality is roughly 8–10 times higher. Clinicians also perceive women as lower risk than men with the same risk profile, leading to undertreatment.

• 03

  Ten-year risk scores fail younger people.

  A 30-year-old with blood pressure of 160 has a 'low' 10-year risk simply because of age, yet a high lifetime risk. Michos and Attia note that at the bottom of the calculator's age range almost no input yields a high 10-year score, and that no trial enrolled people 25–45 long enough to show events prevented — yet no one doubts treating causal factors like hypertension or smoking early.

• 04

  Guidelines still lean on 10-year risk, with modifiers.

  Under the 2019 ACC/AHA primary-prevention guidelines, below 5% 10-year risk lifestyle may suffice; above 20%, a high-intensity statin to cut LDL by 50% or more. Risk-enhancing factors and a coronary calcium score refine decisions, though a zero score is less reassuring under 40 because plaque takes time to calcify.

• 05

  Female-specific factors change risk.

  Menarche before 11 or after 17, preeclampsia and gestational diabetes, and menopause before 45 (especially before 40) are associated with higher cardiovascular risk. PCOS is linked to about a 30–50% increased risk on average; insulin resistance appears in about 95% of obese and 75% of lean women with PCOS.

• 06

  Pregnancy dramatically raises lipids — by design.

  Lipids climb and peak in the third trimester: total cholesterol up about 25–50%, triglycerides about 150–300%, LDL around 66% — normal physiology to supply the fetus. Across the menstrual cycle the swing is small, roughly 10–12 mg/dL in total cholesterol.

• 07

  Familial hypercholesterolemia is undertreated in women.

  FH carries about a 20-fold increased risk and, in women, onset of disease roughly 20–30 years earlier; women with FH lose the usual female advantage, partly because they miss years of statin therapy over pregnancy concerns. Michos notes FH itself doesn't raise malformation or preeclampsia risk, and treatment in pregnancy is a shared decision.

• 08

  Statins work equally well in women.

  A meta-analysis of over 18 randomized trials with more than 40,000 women showed similar relative benefit to men, scaling with each 1 mmol/L (39 mg/dL) LDL reduction. Yet in a survey representing 11 million US women with established disease, women were 45% less likely to be on statins.

• 09

  Much statin intolerance is nocebo.

  Up to 30% of statin-treated patients report muscle symptoms, but blinded trials such as SAMSON suggest up to about 90% of those symptoms also occur on placebo. Michos often uses low doses of rosuvastatin (5–20 mg), notes CoQ10 lacks good evidence but is harmless if patients want it.

• 10

  Non-statin options fill the gap.

  Ezetimibe adds roughly 18–21% LDL lowering; PCSK9 monoclonal antibodies lower LDL about 50–60% and Lp(a) about 25%, with outcome benefit in FOURIER and ODYSSEY; inclisiran, an siRNA, has lipid data from ORION trials. For very high-risk patients she believes optimal LDL may be around 30 or lower.

• 11

  Lp(a) is a risk enhancer even at low LDL.

  Lp(a) has a variable number of kringle IV type 2 repeats (2 to over 40). In the Copenhagen General Population Study, Lp(a) above 50 mg/dL carried risk even with LDL below 70. Investigational drugs pelacarsen and olpasiran lower it 80–90%, but outcome data are pending.

• 12

  Hormone therapy is reasonable for symptomatic women near menopause.

  For symptomatic women under 60 or within 10 years of menopause, Michos sees HRT as appropriate; she generally doesn't start it more than 10 years after menopause or over 65.