The Amgen-sponsored CV Academy 2021 kicked off with international guest speaker Dr Leslee Shaw, Women’s Health Director at the Icahn School of Medicine at Mount Sinai. She discussed the differences in cardiovascular (CV) health between men and women, highlighting how differently the disease can manifest.

More than biology driving differences between men’s and women’s CV health

Dr Shaw explained how at the biological level, there is sexual dimorphism in plaque formation between the sexes. “They can manifest themselves as varied clinical characteristics or presentations, such as more diabetes, hypertension and obesity in women than men. But I cannot talk about the sex differences without acknowledging the gender and cultural issues at play as well,” explained Dr Shaw. “We get varied referral patterns, smaller samples of women in our knowledge base. There are also age and risk-factor related differences as well as novel biomarkers. Females over the age of 13 have higher C-reactive protein levels for example, which mean they exist in a more inflammatory mileu. There’s also race and ethnicity differences that not only drive difference in phenotype, but access to care as well,”¹ she said

Pathologic observations of sex differences

In terms of sudden cardiac death, Dr Shaw presented a graphical representation of typical plaque rupture in men versus women. “In men, you see a necrotic core with an occlusive thrombus. In women, the more common presentation is plaque erosion with an intact fibrous cap and early fibroatheroma.”² She went on to explain the more potent and prognostically significant difference is “not just the non-occlusive nature of plaque formation and lower plaque burden overall, but rather that they are predominantly non-calcified plaques.”³

Dr Shaw’s key differences of note:

1. There is a delay in the increased incidence of calcified plaques in men vs women

Data from the Coronary Artery Calcium Consortium shows the prevalence increases around age 35 in men but age 45 in women. “Over that 10-year gap, women gradually lose oestrogen as they enter a perimenopausal phase. With the menopausal stage the calcified plaque burden increases,”⁴ explained Dr Shaw.

2. Women have more nonobstructuve plaque than men

“I can show lots of examples of this in the invasive as well as the non-invasive literature,” explained Dr Shaw. “Years ago we used to pool the data and really did our patients a disservice, now knowing that there is a huge difference in risk between obstructive and non-obstructive disease among men and women. Nonobstructive CAD in women is prognostically important.^6-8 As we start to peel the layers back, we need to appreciate what’s stabilising the plaques – that could be calcification.⁹ But those that are at high risk of progression are those with a necrotic core and positive remodelling. Lumenograms can be misleading. The PROspective Multicenter Imaging Study for Evaluation of Chest Pain Trial demonstrated how high-risk plaque features are more predictive in women who are younger and with nonobstructive CAD.”^10,11

Where this leaves us is to consider how today’s diagnostic evaluations could be leaving women out. “Today’s procedures aim to detect obstructive disease and women who need coronary revascularisation. That’s kind of a problem, knowing that many have nonobstructive disease and could be high risk because of that. It’s important for us to keep in mind and to consider preventive strategies even though the guidelines don’t address that just yet.” Looking to the future, Dr Shaw left delegates to consider the following sex differences in atherosclerosis:

• Lumen volume and vessel size
• Diffuseness of atheroscleorotic disease
• LV mass and the myocardial area at risk
• Tortuosity
• Obesity, in particular pericardial adiposity and inflammation

This article was commissioned by Amgen Australia. The content is independent and based on studies and the author’s opinion. The views expressed do not necessarily reflect the views of the sponsor.

References

1. Shaw L, et al. J Am Coll Cardiol. 2017;70 (3) 373–388.
2. Yahagi K, et al. Nat Rev Cardiol. 2016 Feb;13(2):79-98
3. Ylä-Herttuala S et al. EHJ 2013;34:3251-8.
4. Shaw L et al, EHJ 2018;39:3727-3735
5. Pepine CJ et al. J Am Coll Cardiol 2015;66(17):1918-33.
6. Min JK et al. J Am Coll Cardiol. 2011;58(8):849-60.
7. Schulman-Marcus J et al. JACC Cardiovasc Imaging. 2016;9(4):364-372.
8. Plank F et al. Neth Heart J 2019;27(5):272-280.
9. Ahmadi A, et al. J Am Coll Cardiol. 2019;74(12):1608-1617.
10. Ferencik M, et al. JAMA Cardiol 2018;3:144-152.
11. Williams MC, et al. Circulation. 2020;141(18):1452-1462.