While loneliness has been regarded as a risk to mental and physical health, there is a lack of current community data covering a broad age range. This study used a large and representative German adult sample to investigate loneliness. Baseline data of the Gutenberg Health Study (GHS) collected between April 2007 and April 2012 (N = 15,010; 35–74 years), were analyzed. Recruitment for the community-based, prospective, observational cohort study was performed in equal strata for gender, residence and age decades. Measures were provided by self-report and interview. Loneliness was used as a predictor for distress (depression, generalized anxiety, and suicidal ideation) in logistic regression analyses adjusting for sociodemographic variables and mental distress. A total of 10.5% of participants reported some degree of loneliness (4.9% slight, 3.9% moderate and 1.7% severely distressed by loneliness). Loneliness declined across age groups. Loneliness was stronger in women, in participants without a partner, and in those living alone and without children. Controlling for demographic variables and other sources of distress loneliness was associated with depression (OR = 1.91), generalized anxiety (OR = 1.21) and suicidal ideation (OR = 1.35). Lonely participants also smoked more and visited physicians more frequently. The findings support the view that loneliness poses a significant health problem for a sizeable part of the population with increased risks in terms of distress (depression, anxiety), suicidal ideation, health behavior and health care utilization.

Masking out air sharing: The effectiveness of masks in preventing the transmission of severe acute respiratory syndrome coronavirus 2 has been debated since the beginning of the COVID-19 pandemic. One important question is whether masks are effective despite the forceful expulsion of respiratory matter during coughing and sneezing. Cheng et al. convincingly show that most people live in conditions in which the airborne virus load is low. The probability of infection changes nonlinearly with the amount of respiratory matter to which a person is exposed. If most people in the wider community wear even simple surgical masks, then the probability of an encounter with a virus particle is even further limited. In indoor settings, it is impossible to avoid breathing in air that someone else has exhaled, and in hospital situations where the virus concentration is the highest, even the best-performing masks used without other protective gear such as hazmat suits will not provide adequate protection. Science , abg6296, this issue p. 1439

OBJECTIVE: The inflammatory and immune systems are altered in type 2 diabetes. Here, the aim was to profile the immune and inflammatory response in subjects with prediabetes and diabetes in a large population-representative sample. RESEARCH DESIGN AND METHODS: In total, 15,010 individuals were analyzed from the population-based Gutenberg Health Study. Glucose status was classified according to HbA1c concentration and history of diagnosis. All samples were analyzed for white blood cells (WBCs), granulocytes, lymphocytes, monocytes, platelets, C-reactive protein (CRP), albumin, fibrinogen, and hematocrit. Interleukin-18 (IL-18), IL-1 receptor antagonist (IL-1RA), and neopterin concentrations were determined in a subcohort. RESULTS: In total, 7,584 men and 7,426 women were analyzed (range 35–74 years), with 1,425 and 1,299 having prediabetes and diabetes, respectively. Biomarkers showed varying dynamics from normoglycemic via subjects with prediabetes to subjects with diabetes: 1) gradual increase (WBCs, granulocytes, monocytes, IL-1RA, IL-18, and fibrinogen), 2) increase with subclinical disease only (lymphocytes and CRP), 3) increase from prediabetes to diabetes only (neopterin), and 4) no variation with glucose status (hematocrit). The strongest relative differences were found for CRP, IL-1RA, and fibrinogen concentrations. Several inflammatory and immune markers were associated with the glucose status independent from cardiovascular risk factors and comorbidities, varied with disease severity and the presence of disease-specific complications in the diabetes subcohort. CONCLUSIONS: The inflammatory and immune biomarker profile varies with the development and progression of type 2 diabetes. Markers of inflammation and immunity enable differentiation between the early preclinical and clinical phases of the disease, disease complications, and progression.

BACKGROUND. Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS. A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS. The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION. The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING. For detailed information per study, see Acknowledgments.

Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce. Systematic phenotyping of CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40–80 years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was done in an independent cohort study (MyoVasc, NCT04064450). The prevalence of telangiectasia/reticular, varicose veins, and CVI was 36.5% [95% confidence interval (CI), 35.6–37.4%], 13.3% [12.6–13.9%], and 40.8% [39.9–41.7%], respectively. Age, female sex, arterial hypertension, obesity, smoking, and clinically overt cardiovascular disease were identified as clinical determinants of CVI. Higher CEAP classes were associated with a higher predicted 10-year risk for incident cardiovascular disease in individuals free of cardiovascular disease (n = 9923). During a mean follow-up of 6.4 ± 1.6 years, CVI was a strong predictor of all-cause death independent of the concomitant clinical profile and medication [hazard ratio (HR) 1.46 (95% CI 1.19–1.79), P = 0. 0003]. The association of CVI with an increased risk of all-cause death was externally validated in the MyoVasc cohort [HR 1.51 (95% CI 1.11–2.05), P = 0.009]. Chronic venous insufficiency is highly prevalent in the population and is associated with the presence of cardiovascular risk factors and disease. Individuals with CVI experience an elevated risk of death, which is independent of age and sex, and present cardiovascular risk factors and comorbidities. Chronic venous insufficiency is highly prevalent in the general population and associated with arterial cardiovascular disease and an increased risk of all-cause mortality.