Proceedings from the scientific symposium: Sex differences in cardiovascular disease and implications for therapies

Abstract

A consortium of investigator-thought leaders was convened at the Heart Institute at Cedars-Sinai Medical Center and produced the following summary points: POINT 1: Important sex differences exist in cardiovascular disease (CVD) that affect disease initiation, diagnosis, and treatment.

Implication: Research that acknowledges these differences is needed to optimize outcomes in women and men. POINT 2: Atherosclerosis is qualitatively and quantitatively different in women and men; women demonstrate more plaque erosion and more diffuse plaque with less focal artery lumen intrusion.

Implication: Evaluation of CVD strategies that include devices should be used to explore differing anatomical shapes and surfaces as well as differing drug coating and eluting strategies. POINT 3: Bone marrow progenitor cells (PCs) engraft differently based on the sex of the donor cell and the sex of the recipient.

Implication: PC therapeutic studies need to consider the sex of cells of the source and the recipient. POINT 4: Women have a greater risk of venous but not arterial thrombosis compared with men, as well as more bleeding complications related to anticoagulant treatment. Several genes coding for proteins involved in hemostasis are regulated by sex hormones.

Implications: Research should be aimed at evaluation of sex-based differences in response to anticoagulation based on genotype. POINT 5: Women and men can have differences in pharmacological response.

Implication: Sex-specific pharmacogenomic studies should be included in pharmacological development. POINT 6: CVD progression results from an imbalance of cell injury and repair in part due to insufficient PC repair, which is affected by sex differences, where females have higher circulating levels of PCs with greater rates of tissue repair.

Implication: CVD regenerative strategies should be directed at learning to deliver cells that shift the recipient balance from injury toward repair. CVD repair strategies should ideally be tested first in females to have the best chance of success for proof-of-concept.

FIG. 1.

Cardiovascular Disease (CVD) mortality trends in women and men. CVD disease mortality trends, U.S. 1979–2004. Source: NCHS and NHLBI (2008).

FIG. 2.

Sex differences in atherosclerotic plaque disruption. Reprinted with permission from Burke et al. Circulation 1998;97:2110–2116.

FIG. 3.

Female progenitor cells (PCs) are more beneficial for atherosclerotic plaque burden. Sex-dependent attenuation of plaque growth after treatment with bone marrow mononuclear cells (BMNCs). Reprinted with permission from Nelson et al. Circulation Research 2007;101:1319–1327.

FIG. 4.

Sex differences in aspirin therapy for CVD prevention. Reprinted with permission from Redberg et al. N Engl J Med 2005;352:1293–1304.

FIG. 5.

Sex differences in acute myocardial infarction outcomes. Reprinted with permission from Vaccarino et al. N Engl J Med 1999;341:217–225.