Sex as a Biological Variable in Atherosclerosis.

Area of Science:

• Cardiovascular Research
• Vascular Biology
• Sex as a Biological Variable

Background:

• Atherosclerosis is a major cause of heart attack and stroke, with known sex disparities.
• Limited research rigorously addresses sex as a biological variable in atherosclerosis mechanisms.
• While younger women are protected, older women surpass men in myocardial infarction incidence.

Purpose of the Study:

• To review available data on sex differences in atherosclerosis mechanisms.
• To highlight the limited preclinical studies examining both sexes.
• To emphasize the need to understand sex-specific mechanisms for precision medicine.

Main Methods:

• Review of histological and imaging studies in human and animal models.
• Analysis of preclinical atherosclerosis models examining sex as a variable.
• Focus on plaque inflammation and size as indicators of vulnerability.

Main Results:

• Male animals exhibit more inflamed but smaller atherosclerotic plaques than females.
• Plaque inflammation, not size, correlates with sex differences in ischemic events and mortality.
• Preclinical studies rarely perform well-powered direct statistical comparisons for sex.

Conclusions:

• Plaque inflammation appears more relevant than plaque size for understanding sex-specific atherosclerosis mechanisms.
• Failure to include both sexes and age in studies represents missed opportunities.
• Understanding sex-specific mechanisms is critical for developing precision medicine strategies against cardiovascular disease.