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Objective As severity of outcome in COVID‐19 is disproportionately higher among individuals with obesity, smokers, patients with hypertension, kidney disease, chronic pulmonary disease, coronary heart disease (CHD), and/or type 2 diabetes (T2D), serum levels of ACE2, the cellular entry point for the coronavirus SARS‐CoV‐2, were examined in these high‐risk groups. Methods Associations of ACE2 levels to smokers and patients with hypertension, T2D, obesity, CHD, or COPD were investigated in a single center population‐based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavík Study (AGES‐RS) of the elderly (mean age 75 ± 6 years), using multiple linear regression analysis. Results Serum levels of ACE2 were higher in smokers and individuals with T2D and/or obesity while they were unaffected in the other patient groups. Conclusion ACE2 levels are higher in some patient groups with comorbidities linked to COVID‐19 including obesity and T2D and as such may have an emerging role as a circulating biomarker for severity of outcome in the disease.

PURPOSE Limited information is available on the effects of cardiac rehabilitation (CR) on individuals with heart failure (HF) in Iceland. The aim of this study was to analyze whether CR yielded increased physical capacity (PC) (w/kg) as measured by maximum exercise test at the end of the training period. MATERIALS AND METHODS This is a retrospective data study from January 2010 to June 2018. Participants were patients with HF and also patients with ejection fraction (EF) 45% or less. Age and other diagnoses did not limit participation. Information about EF and exercise test at the beginning and end of the training period had to be recorded. Relative change in PC on these tests was evaluated by general linear models for repeated measurements. During the study period, 112 participants were enrolled, 27 did not finish the training period and 9 had incomplete data. Data from 76 participants aged 36-83 were analyzed. RESULTS Participants' PC increased on average by 16% (p

Age-related macular degeneration (AMD) is one of the most frequent causes of visual impairment in the elderly population. The overall etiology of AMD is complex and still poorly understood, though age, obesity, smoking, and high-density lipoprotein are known risk factors. In one of the first successful reported genome-wide association studies (GWAS), common genetic variants were strongly associated with AMD, including variants within the complement factor H (CFH) gene. To date, 34 genomic regions have been linked to AMD; however, the genes that mediate the risk remain largely unknown, indicating that novel approaches to identifying causal candidates are needed. Recent advances in proteomic technology have exposed the serum proteome’s depth and complexity. In the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS), a broad population-based study of the elderly (N = 5764), levels of 4137 human serum proteins and associated networks were integrated with established genetic risk loci for AMD, revealing many predicted as well as novel proteins and pathways, linked to the disease. Serum proteins were also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study of five proteins associated with AMD found CFHR1, CFHR5, and FUT5 to be causally related to the disease, all of which were directionally consistent with the observational estimates. This study provides a robust and unique framework for elucidating the pathobiology of AMD.

With the growing number of genetic association studies, the genotype-phenotype atlas has become increasingly more complex, yet the functional consequences of most disease associated alleles is not understood. The measurement of protein level variation in solid tissues and biofluids integrated with genetic variants offers a path to deeper functional insights. Here we present a large-scale proteogenomic study in 5,368 individuals, revealing 4,113 independent associations between genetic variants and 2,099 serum proteins, of which 37% are previously unreported. The majority of bothcis- andtrans-acting genetic signals are unique for a single protein, although our results also highlight numerous highly pleiotropic genetic effects on protein levels and demonstrate that a protein’s genetic association profile reflects certain characteristics of the protein, including its location in protein networks, tissue specificity and intolerance to loss of function mutations. Integrating protein measurements with deep phenotyping of the cohort, we observe substantial enrichment of phenotype associations for serum proteins regulated by established GWAS loci, and offer new insights into the interplay between genetics, serum protein levels and complex disease.

Background The Icelandic population is aging like other populations in the world, the life expectancy is high, and the national focus is to help people to age in their own homes. The objectives of this research was to describe 17 years of demographic changes among outpatient physical therapy (OPT) clients and to determine if these changes reflect aging in the total population. Methods Data was obtained from a national registry with information on all OPT clients reimbursed by Icelandic Health Insurance from 1999 to 2015, and general population data from the Statistics Iceland registry covering the same 17 years. Simple counts, proportions, Rate Ratios (RR) and 95 % Confidence Intervals (CI) were used to describe and compare the two time-points (1999 and 2015) in both populations, and regression analyses were used to estimate linear changes for each of these 17 years. Results Comparing the endpoints of the 17-year period, the proportion of older adults within the total OPT clientele increased by 23 % (from 18.3 % to 1999 to 23.5 % in 2015; RR 1.23; 95 %CI 1.19–1.27).) while in the general Icelandic population, the proportion of older adults increased by 15 % (from 11.6 % to 1999 to 13.5 % in 2015; RR 1.15; 95 % CI 1.1–1.21). For each of these 17 years, there was an overall 5 % yearly increase in the rate of older adults from the general older Icelandic population who used an OPT (accounting for population aging), and an overall 3.5 % yearly increase in the proportional contribution of older adults to the total OPT clientele. Adjusting for sex and older age group revealed that this increase in rate and proportion was most pronounced among ≥ 85-year-old men. Conclusions This case of Iceland is an example of how health-related and population-based registers may potentially be used to routinely inform and facilitate optimal planning of future health care services for older adults.

Importance Recent reports have shown that hypertension is the most common comorbidity associated with mortality in the current coronavirus disease 2019 (COVID-19). This has been related to the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) as animal studies indicate that these medications increase levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2. This has prompted clinicians to recommend discontinuing ACEIs and ARBs. Objective To examine the effect of ACEIs or ARBs treatment on serum levels of ACE2 and other key enzymes in the renin-angiotensin system (RAS). Design, Setting, and Participants A single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75±6 years) stratified by ACEIs (N = 699) or ARBs (N = 753) treatment. Main Outcomes and Measures The AGES-RS study population was stratified by ACEIs and ARBs medication use and compared for age, body mass index (BMI) (kg/m2), hypertension and type 2 diabetes (T2D) as well as serum levels of renin, ACE and ACE2. Results While renin and ACE levels were significantly raised in serum of individuals on ACEIs or ARBs treatments, the ACE2 levels remained unaffected. Conclusions and Relevance Treatment with ACEIs or ARBs does not raise ACE2 levels in serum. Therefore, the present study does not support the proposed discontinuation of these medications among patients affected with COVID-19.

AimsSeverity of outcome in COVID-19 is disproportionately higher among the obese, males, smokers, those suffering from hypertension, kidney disease, coronary heart disease (CHD) and/or type 2 diabetes (T2D). We examined if serum levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2, were altered in these high-risk groups.MethodsAssociations of serum ACE2 levels to hypertension, T2D, obesity, CHD, smokers and males in a single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75±6 years).ResultsSmokers, males, and individuals with T2D or obesity have altered serum levels of ACE2 that may influence productive infection of SARS-CoV-2 in these high-risk groups.ConclusionACE2 levels are upregulated in some patient groups with comorbidities linked to COVID-19 and as such may have an emerging role as outcome in COVID-19. a circulating biomarker for severity of severity of outcome in COVID-19.Key PointsQuestionSeverity of outcome in COVID-19 is disproportionately higher among the obese, males, smokers, those suffering from hypertension, kidney disease, coronary heart disease (CHD) and/or type 2 diabetes (T2D). Thus, we asked if the coronavirus SARS-CoV-2 receptor ACE2 was altered in the sera from these high-risk groups?FindingsIn a single center population-based study of 5457 Icelanders, the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS), we find that ACE2 levels are significantly elevated in serum from smokers, obese and diabetic individuals, while reduced in males.MeaningThese results demonstrate that individuals with comorbidities associated with infection of SARS-CoV-2 in these individuals. severe outcome in COVID-19 have altered serum levels of ACE2 that may influence productive

Circulating proteins are prognostic for human outcomes including cancer, heart failure, brain trauma and brain amyloid plaque burden. A deep serum proteome survey recently revealed close associations of serum protein networks and common diseases. The present study reveals unprecedented number of individual serum proteins that overlap genetic signatures of diseases emanating from different tissues of the body. Here, 54,469 low-frequency and common exome-array variants were compared with 4782 protein measurements in the serum of 5343 individuals of the deeply annotated AGES Reykjavik cohort. Using a study-wide significant threshold, 2019 independent exome array variants affecting levels of 2135 serum proteins were identified. These variants overlapped genetic loci for hundreds of complex disease traits, emphasizing the emerging role for serum proteins as biomarkers of and potential causative agents of multiple diseases.