Sex Differences in the Association between Inflammation and Ischemic Heart Disease

Abstract

Background Inflammation plays a fundamental role in mediating all stages of atherosclerosis. Given the higher prevalence of inflammatory rheumatologic conditions in women and the female propensity towards worse cardiovascular outcomes, refined strategies are needed to better identify the high-risk female cardiovascular phenotype. Objectives This article aims to assess sex-specific links between inflammatory processes and the development and progression of ischemic heart disease. Patients and Methods The relationship between vertebral bone marrow metabolism—a marker of inflammation—and myocardial injury was retrospectively assessed in 294 patients (28.6% women, mean age: 66.9 ± 10.0 years) who underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and 99mTc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). Results A significant increase in 18F-FDG bone marrow uptake was observed in women with impaired myocardial perfusion (SPECT-MPI) as compared to women with normal myocardial perfusion (standardized uptake value [SUV]: 2.2 ± 1.2 vs. 1.7 ± 0.5, p = 0.013), while no such difference was observed in men (SUV: 1.6 ± 0.8 vs. 1.6 ± 0.4, p = 0.372). Furthermore, a significant inverse correlation between left ventricular ejection fraction (LVEF) and bone marrow metabolism was seen in women (r = –0.229, p = 0.037), but not in men (r = –0.075, p = 0.289). Accordingly, in women, but not in men, bone marrow activity was identified as an independent predictor of both, reduced LVEF (β-coefficient, –4.537; p = 0.040) and impaired myocardial perfusion (β-coefficient, 0.138; p = 0.014). Conclusion A strong link between bone marrow metabolism and impaired myocardial function and perfusion was observed in women, but not in men. Our data suggest that novel biomarkers of inflammation might help to identify women at risk for ischemic cardiomyopathy and to tailor disease management to the female cardiovascular phenotype.

The Neuro-Inflammatory-Vascular Circuit: Evidence for a Sex-Dependent Interrelation?

“…A recent study focusing on myocardial function, perfusion, and metabolic amygdalar activity revealed an association between elevated amygdalar activity and impaired myocardial perfusion/function. Notably, these associations were observed in women, but not in men (Fiechter et al, 2019a). Further, resting amygdalar activity was not affected by high coronary artery calcium scoring, suggesting that the extend of myocardial injury, rather than atherosclerotic plaque burden, is mainly responsible for an enhanced neural stress response in the female population.…”

“…This is a major omission given that experimental studies in rats indicate a twofold higher susceptibility to lethal effects of colchicine in females (Wiesenfeld et al, 2007). While cardiovascular pathologies and outcomes have been associated with a higher level of inflammatory activity, it was only recently demonstrated that an upregulated metabolic activity of the vertebral bone marrow, a surrogate marker of inflammation, is a strong and independent predictor of myocardial injury, suggesting that inflammatory biomarkers play a significant role in the development and progression of CAD toward myocardial ischemia and fibrosis (Fiechter et al, 2019a). Most intriguingly, these observations were sex-dependent with a significant association of inflammation and myocardial function and perfusion in women, but not in men.…”

Myocardial 18F-FDG Uptake Pattern for Cardiovascular Risk Stratification in Patients Undergoing Oncologic PET/CT

“…Quantitative myocardial 18 F-FDG uptake was measured by serially placing volumes of interest (VOI) using AW Server software (version 3.2, GE Healthcare) as previously described and validated [ 24 , 25 , 26 , 27 , 28 ]. VOIs were placed as follows: VOI 1 was placed at the mid-ventricular septum, VOI 2 at the anterior apex, VOI 3 at the mid-ventricular lateral wall, VOI 4 basal anterior wall, VOI 5 at the posterior apex, VOI 6 at the liver in an area of low 18 F-FDG uptake, and VOI 7 at the aortic arch.…”

Gender Specificity and Interpretation of Functional Cardiac Imaging: Let's Talk about Sex

“…In their present study, Fiechter et al report from nuclear medicine that for women, a strong association exists between inflammation, as measured by vertebral bone marrow metabolism, and impaired myocardial function and perfusion, as assessed by single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI). 1 Among a total of 294 patients (28.6% women, mean age 67 years old) who underwent 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography and 99 Tc-tetrofosmin SPECT-MPI, a significant increase in 18 F-FDG bone marrow uptake was observed in women with impaired myocardial perfusion as compared with normal myocardial perfusion (standardized uptake 2.2 AE 1.2 vs. 1.7 AE 1.2, p ¼ 0.013), while no differences were found in men (1.6 AE 0.8 vs. 1.6 AE 0.4, p ¼ 0.372). In addition, a significant inverse correlation between left ventricular ejection fraction and bone marrow metabolism was seen in women (r ¼ -0.229, p ¼ 0.037), but not in men (r ¼ -0.075, p ¼ 0.289).…”