Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study.

Mean platelet volume (MPV), a measure of platelet size, is a potential biological marker of platelet function. To date, a comprehensive analysis including known genetic and nongenetic factors that determine MPV is still lacking. MPV has been evaluated in 15 010 individuals from the population-based Gutenberg Health Study. Genetic information was available for 4175 individuals. Our results showed that age (ß, 0.0346; 95% confidence interval [CI], 0.0255 to 0.0436), cardiovascular risk factors (CVRFs) such as smoking (ß, 0.178; 95% CI, 0.128 to 0.229), hypertension (ß, 0.05; 95% CI, 0.00289 to .0981), and high glucose level (ß, 0.00179; 95% CI, 0.0006 to 0.00299) were linked with higher MPV in males only. Intake of oral contraceptives (ß, 0.150; 95% CI, 0.0649 to 0.236) and menstruation (ß, 0.123; 95% CI, 0.0231 to 0.224) were strongly associated with higher MPV in females. Seven single nucleotide polymorphisms (SNPs) for females and 4 SNPs for males were associated with higher MPV. The full model, including age, CVRFs, laboratory parameters, medications, and genetic variation, explained 20.4% of the MPV variance in females and 18.6% in males. The curves of cumulative mortality, stratified for sex, showed worse survival for males only with MPV > 9.96 fL vs MPV ≤ 9.96 fL (P < .0001). This study provides evidence for heterogeneity in the profile of determinants for MPV between sexes. The observed interactions between genetic variability, CVRFs, and MPV and its association with the development of cardiovascular disease or thrombotic risk need to be further investigated.

T1 and T2 mapping to detect chronic inflammation in cardiac magnetic resonance imaging in heart failure with reduced ejection fraction.

AIMS: The purpose of this retrospective single-centre study was to evaluate the non-invasive detection of endomyocardial biopsy (EMB)-established chronic myocardial inflammation in patients with heart failure with reduced ejection fraction (HFrEF) using T1 and T2 mapping. METHODS AND RESULTS: The study population consisted of 52 retrospectively identified HFrEF patients who underwent EMB and cardiac magnetic resonance imaging at 3 Tesla. EMB was defined according to the position statement of the European Society of Cardiology and served as reference to identify inflammation in all patients. A control group of healthy volunteers with prior cardiac magnetic resonance imaging studies (n = 58) was also identified. Global and segmental T1 and T2 values as well as septal measurements and tissue heterogeneity parameters were calculated. Out of the 52 patients with HFrEF, 33 patients had myocardial inflammation detected by EMB, while 19 patients were EMB negative for inflammation. Mean left ventricular ejection fraction was 31% in both groups (P = 0.97). Global T1 and T2 values in HFrEF patients were significantly higher compared with healthy controls (T1 1275 ± 69 ms vs. 1,175 ± 44 ms, P < 0.001; T2 40.0 ± 3.4 ms vs. 37.9 ± 1.6 ms, P < 0.001). The distribution of T1 and T2 values between patients with and without EMB-proven chronic myocardial inflammation was not statistically different when regarding global (T1 1292 ± 71 ms vs. 1266 ± 67 ms, P = 0.26; T2 40.0 ± 2.6 ms vs. 40.0 ± 3.9 ms, P = 1.0), septal (T1 1299 ± 63 ms vs. 1289 ± 76 ms, P = 0.76; T2 40.1 ± 3.5 ms vs 40.0 ± 6.4 ms, P = 0.49) or maximum segmental values (T1 1414 ± 111 ms vs. 1363 ± 88 ms, P = 0.15; T2 47.3 ± 5.2 ms vs. 48.8 ± 11.8 ms, P = 0.53). Mean absolute deviation of segmental T1 and T2 values and log-transformed pixel-wise standard deviation as parameters of tissue heterogeneity did not reveal statistical significant differences between inflammation-positive and inflammation-negative HFrEF patients (all P > 0.4). CONCLUSIONS: Conventionally performed quantitative T1 and T2 mapping values significantly correlated with prevalence of HFrEF but did not discriminate HFrEF patients with or without chronic myocardial inflammation in our cohort. This suggests that EMB is the preferred method to detect chronic myocardial inflammation in HFrEF.