Quantile-specific heritability of plasma fibrinogen concentrations

Background Fibrinogen is a moderately heritable blood protein showing different genetic effects by sex, race, smoking status, pollution exposure, and disease status. These interactions may be explained in part by “quantile-dependent expressivity”, where the effect size of a genetic variant depends upon whether the phenotype (e.g. plasma fibrinogen concentration) is high or low relative to its distribution. Purpose Determine whether fibrinogen heritability (h2) is quantile-specific, and whether quantile-specific h2 could account for fibrinogen gene-environment interactions. Methods Plasma fibrinogen concentrations from 5689 offspring-parent pairs and 1932 sibships from the Framingham Heart Study were analyzed. Quantile-specific heritability from offspring-parent (βOP, h2 = 2βOP/(1+rspouse)) and full-sib regression slopes (βFS, h2 = {(1+8rspouseβFS)0.05–1}/(2rspouse)) were robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. Results Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted fibrinogen distribution when estimated from βOP (Ptrend = 5.5x10-6): 0.30±0.05 at the 10th, 0.37±0.04 at the 25th, 0.48±0.05 at the 50th, 0.61±0.06 at the 75th, and 0.65±0.08 at the 90th percentile, and when estimated from βFS (Ptrend = 0.008): 0.28±0.04 at the 10th, 0.31±0.04 at the 25th, 0.36±0.03 at the 50th, 0.41±0.05 at the 75th, and 0.50±0.06 at the 90th percentile. The larger genetic effect at higher average fibrinogen concentrations may contribute to fibrinogen’s greater heritability in women than men and in Blacks than Whites, and greater increase from smoking and air pollution for the FGB -455G>A A-allele. It may also explain greater fibrinogen differences between: 1) FGB -455G>A genotypes during acute phase reactions than usual conditions, 2) GTSM1 and IL-6 -572C>G genotypes in smokers than nonsmokers, 3) FGB -148C>T genotypes in untreated than treated diabetics, and LPL PvuII genotypes in macroalbuminuric than normoalbuminuric patients. Conclusion Fibrinogen heritability is quantile specific, which may explain or contribute to its gene-environment interactions. The analyses do not disprove the traditional gene-environment interpretations of these examples, rather quantile-dependent expressivity provides an alternative explanation that warrants consideration.

Cardiovascular disease protein biomarkers are associated with kidney function: the Framingham Heart Study

Background. Biomarkers common to chronic kidney disease (CKD) and cardiovascular disease (CVD) may reflect early impairments underlying both diseases. Methods. We evaluated associations of 71 CVD-related plasma proteins measured in 2,873 Framingham Heart Study (FHS) Offspring cohort participants with cross-sectional continuous eGFR and with longitudinal change in eGFR from baseline to follow-up (ΔeGFR). We also evaluated the associations of the 71 CVD proteins with the following dichotomous secondary outcomes: prevalent CKD stage ≥3(cross-sectional), new-onset CKD stage ≥3 (longitudinal), and rapid decline in eGFR (longitudinal). Proteins significantly associated with eGFR and ΔeGFR were subsequently validated in 3,951 FHS Third Generation cohort participants and were tested using Mendelian randomization (MR) analysis to infer putatively causal relations between plasma protein biomarkers and kidney function. Results. In cross-sectional analysis, 37 protein biomarkers were significantly associated with eGFR at FDR<0.05 in the FHS Offspring cohort and 20 of these validated in the FHS Third Generation cohort at p<0.05/37. In longitudinal analysis, 27 protein biomarkers were significantly associated with ΔeGFR at FDR<0.05 and 12 of these were validated in the FHS Third Generation cohort at p<0.05/27. Additionally, 35 protein biomarkers were significantly associated with prevalent CKD, five were significantly associated with new-onset CKD, and 17 were significantly associated with rapid decline in eGFR. MR suggested putatively causal relations of melanoma cell adhesion molecule (MCAM; -0.011±0.003 mL/min/1.73m2, p=5.11E-5) and epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1; -0.006±0.002 mL/min/1.73m2, p=0.0001) concentration with eGFR. Discussion/Conclusions: Eight protein biomarkers were consistently associated with eGFR in cross-sectional and longitudinal analysis in both cohorts and may capture early kidney impairment; others were implicated in association and causal inference analyses. A subset of CVD protein biomarkers may contribute causally to the pathogenesis of kidney impairment and should be studied as targets for CKD treatment and early prevention.

Plant-based diets and incident cardiovascular disease and all-cause mortality in African Americans: A cohort study

Background Prior studies have documented lower cardiovascular disease (CVD) risk among people with a higher adherence to a plant-based dietary pattern. Non-Hispanic black Americans are an understudied group with high burden of CVD, yet studies of plant-based diets have been limited in this population. Methods and findings We conducted an analysis of prospectively collected data from a community-based cohort of African American adults (n = 3,635) in the Jackson Heart Study (JHS) aged 21–95 years, living in the Jackson, Mississippi, metropolitan area, US, who were followed from 2000 to 2018. Using self-reported dietary data, we assigned scores to participants’ adherence to 3 plant-based dietary patterns: an overall plant-based diet index (PDI), a healthy PDI (hPDI), and an unhealthy PDI (uPDI). Cox proportional hazards models were used to estimate associations between plant-based diet scores and CVD incidence and all-cause mortality. Over a median follow-up of 13 and 15 years, there were 293 incident CVD cases and 597 deaths, respectively. After adjusting for sociodemographic characteristics (age, sex, and education) and health behaviors (smoking, alcohol intake, margarine intake, physical activity, and total energy intake), no significant association was observed between plant-based diets and incident CVD for overall PDI (hazard ratio [HR] 1.06, 95% CI 0.78–1.42, p-trend = 0.72), hPDI (HR 1.07, 95% CI 0.80–1.42, p-trend = 0.67), and uPDI (HR 0.95, 95% CI 0.71–1.28, p-trend = 0.76). Corresponding HRs (95% CIs) for all-cause mortality risk with overall PDI, hPDI, and uPDI were 0.96 (0.78–1.18), 0.94 (0.76–1.16), and 1.06 (0.86–1.30), respectively. Corresponding HRs (95% CIs) for incident coronary heart disease with overall PDI, hPDI, and uPDI were 1.09 (0.74–1.61), 1.11 (0.76–1.61), and 0.79 (0.52–1.18), respectively. For incident total stroke, HRs (95% CIs) for overall PDI, hPDI, and uPDI were 1.00 (0.66–1.52), 0.91 (0.61–1.36), and 1.26 (0.84–1.89) (p-trend for all tests > 0.05). Limitations of the study include use of self-reported dietary intake, residual confounding, potential for reverse causation, and that the study did not capture those who exclusively consume plant-derived foods. Conclusions In this study of black Americans, we observed that, unlike in prior studies, greater adherence to a plant-based diet was not associated with CVD or all-cause mortality.

Hazardous alcohol consumption and problem drinking in Norwegian and Russian women and men: The Tromsø Study 2015–2016 and the Know Your Heart study 2015–2018

Aim: Harmful use of alcohol is a worldwide public health concern. Cultural differences may affect responses to questions on alcohol problems, making international comparisons difficult. We aimed to compare self-reported alcohol consumption and problem drinking between Norwegian and Russian populations. Methods: We used data from women and men aged 40–69 years participating in the Tromsø Study seventh survey (Tromsø7, N=17646, participation 65%), Tromsø (2015–2016), Norway, and the Know Your Heart study (KYH, N=4099, participation 51%), Arkhangelsk and Novosibirsk (2015–2018), Russia. Alcohol consumption and problem drinking were measured by the Alcohol Use Disorders Identification Test (AUDIT) via questionnaires (Tromsø7) and interviews (KYH). We compared AUDIT scores and components between populations, by sex. Results: Non-drinking was more commonly reported in KYH compared with Tromsø7 (men 15.5% versus 4.9%, women 13.3% versus 7.3%). In men, hazardous consumption (41.4% versus 31.5%) and problem drinking (24.8% versus 19.6%) was higher in KYH compared with Tromsø7, but opposite for women (6.5% versus 12.0%, and 2.3% versus 5.8%). KYH men were less likely to report problem drinking behaviours than Tromsø7 men, with the exception of needing a drink first thing in the morning (13.2% versus 2.4%). KYH women consistently reported less consumption and problem drinking than Tromsø7 women. Conclusions: We found between-study differences in hazardous drinking, but in men these were lower than suggested by differences in country-level statistics on alcohol consumption and alcohol-related health-harms. Study sample selection, stronger social desirability bias effects in the Russian samples, and cultural differences in responding could have affected the results.

Eponyms in the human heart anatomy

The present time is characterized by an increase in the pace of life, and medicine is no exception. Often, when analyzing the medical literature, specialists are faced with the fact that in different publications almost the same structure has a different name, which causes misunderstanding among specialists in various medical fields. This is especially true for clinicians who use the convenient anatomical names of fundamental scientists such as morphologists. As these names, terms from the International Anatomical Nomenclature are used, along with which, especially in clinical anatomy and medicine, eponymous names are accepted. The use of the latter can also be misunderstood, because eponyms are absent in modern anatomical terminology. However, additional knowledge of eponyms, along with common terms, gives the opportunity to look into the past and honor the memory of those who first described the structures. The paper attempts to systematize the names - eponyms of human heart structures. The need for such work exists because many structures have several eponymous names. In addition, if you arrange the terms in the chronological order of their occurrence, you can trace the main stages in the history of the human heart study. Despite the large number of eponymous names for the same structure and the doubtful attribution of some authors, the work lists only the most common eponyms in domestic and foreign literature, about the origin and authors of which reliable information was found. In 1955, at the IV International Congress of Anatomists in Paris (Paris Anatomical Nomenclature, PNA), eponymous names were excluded from the terminology. There are a number of objective reasons for this, but at the same time, the main function of eponyms is lost - the preservation and transmission to descendants the memory of major figures of medical science who made a significant contribution to its development. Therefore, despite the exclusion of eponyms from the official terminology, these terms are widely used today both at the departments of universities in the world, and in clinical literature and practice.

Association Between Occupational Sitting With High Sensitivity C-Reactive Protein: The Jackson Heart Study

Modifiable, behavioral risk factors like occupational sitting may contribute to inflammation, an important cardiovascular risk factor. This study evaluated the association of self-reported occupational sitting with changes in c-reactive protein (CRP) and the role of sex. We examined occupational sitting and baseline CRP levels for 2889 African American participants in the Jackson Heart Study. Four multivariable linear regression models were estimated to determine the association of occupational sitting and CRP. Analyses were conducted in 2020. The mean age was 50.8 years and 61% were female. Participants who reported occupational sitting as “often/always” had CRP levels of 4.9±6.8 mg/L, “sometimes” had levels of 4.8±8.1 mg/L, and “never/seldom” had levels of 4.3±6.8 mg/L. In the unadjusted model, “often/always” engaging in occupational sitting was significantly associated with higher levels of CRP when compared to “never/seldom” ( P < .05). This differed by sex with female participants who reported “often/always” occupational sitting had CRP levels of 6.0±7.6 mg/L compared to only 5.1±6.9 mg/L for “never/seldom.” Neither the overall association nor the female-specific association remained statistically significant in the adjusted models. We found an association between occupational sitting and inflammation, measured by CRP. This association varied by sex but did not remain significant after fully adjusting for covariates.