Diabetes Genetic Clusters and Clinical Outcomes in American Indians.

Unlabelled: Diabetes has a large medical and public health impact in American Indians. Studies have used genetic data to distinguish type 1 diabetes (T1D) and type 2 diabetes (T2D) and uncover biologic mechanisms underlying T2D clinical heterogeneity. We applied a T1D polygenic score (PS) to 3,084 American Indians (mean age 56 years, 58% women, 39% diabetes).

DNA Methylation Signatures of Cardiovascular Health Provide Insights Into Diseases.

Background: The association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.

Methods: We calculated the American Heart Association's Life's Essential 8 score to reflect CVH in 5 cohorts with diverse backgrounds (mean age 54 years, 55% women, and enrollment year ranging from 1989 to 2012). Epigenome-wide association studies (EWAS) for Life's Essential 8 score were conducted, followed by bioinformatic analyses.

Associations Between Urinary Metal Levels and Incident Heart Failure: A Multi-Cohort Analysis.

Background: Environmental metals are recognized cardiovascular disease risk factors, yet the role of metal exposure in heart failure (HF) risk remains understudied.

Objectives: This study aims to evaluate the prospective association of urinary metals with incident HF across 3 geographically and ethnically/racially diverse cohorts: MESA (Multi-Ethnic Study of Atherosclerosis) and SHS (Strong Heart Study) in the United States, and the Hortega Study in Spain.

Methods: Adults 18-85 years of age in MESA (n = 6,601), SHS (n = 2,917), and Hortega (n = 1,300) were followed up to 20 years.

Longitudinal Lipidomic Profile of Subclinical Peripheral Artery Disease in American Indians: The Strong Heart Family Study.

Introduction: Peripheral artery disease (PAD) and dyslipidemia are both independent predictors of cardiovascular disease, but the association between individual lipid species and subclinical PAD, assessed by ankle-brachial index (ABI), is lacking in large-scale longitudinal studies.

Methods: We used liquid chromatography-mass spectrometry to repeatedly measure 1,542 lipid species from 1,886 American Indian adults attending 2 clinical examinations (mean ~5 years apart) in the Strong Heart Family Study. We used generalized estimating equation models to identify baseline lipid species associated with change in ABI and the Cox frailty regression to examine whether lipids associated with change in ABI were also associated with incident coronary heart disease (CHD).

Lipidomic Markers of Processed Meat and Unprocessed Red Meat Intake and Risk of Diabetes in American Indians.

Objective: To identify lipidomic markers of habitual unprocessed red meat and processed meat intake and evaluate their associations with diabetes risk in American Indians.

Research Design And Methods: We studied 1,816 participants from the Strong Heart Family Study. Using untargeted liquid chromatography-mass spectrometry, we quantified 1,542 lipids (518 known) in fasting plasma at baseline and follow-up (∼5 years apart).

A scan of pleiotropic immune mediated disease genes identifies novel determinants of baseline FVIII inhibitor status in hemophilia A.

Hemophilia-A (HA) is the X-linked bleeding disorder caused by heterogeneous factor (F)VIII gene (F8)-mutations and deficiencies in plasma-FVIII-activity that prevent intrinsic-pathway mediated coagulation-amplification. Severe-HA patients (HAPs) require life-long infusions of therapeutic-FVIII-proteins (tFVIIIs) but ~30% develop neutralizing-tFVIII-antibodies called "FVIII-inhibitors (FEIs)". We investigated the genetics underlying the variable risk of FEI-development in 450 North American HAPs (206 and 244 respectively self-reporting black-African- or white-European-ancestry) by analyzing the genotypes of single-nucleotide-variations (SNVs) in candidate immune-mediated-disease (IMD)-genes using a binary linear-mixed model of genetic association with baseline-FEI-status, the dependent variable, while simultaneously accounting for their genetic relationships and heterogeneous-F8-mutations to prevent the statistical problem of non-independence.

Associations of Prepandemic Lung Function and Structure with COVID-19 Outcomes: The C4R Study.

Increased risk of coronavirus disease (COVID-19) hospitalization and death has been reported among patients with clinical lung disease. To test the association of objective measures of prepandemic lung function and structure with COVID-19 outcomes in U.S.

Demographic and Clinical Factors Associated With SARS-CoV-2 Anti-Nucleocapsid Antibody Response Among Previously Infected US Adults: The C4R Study.

Despite the availability of effective vaccines and a recent decrease in annual deaths, COVID-19 remains a leading cause of death. Serological studies provide insights into host immunobiology of adaptive immune response to infection, which holds promise for identifying high-risk individuals for adverse COVID-19 outcomes. We investigated correlates of anti-nucleocapsid antibody responses following SARS-CoV-2 infection in a US population-based meta-cohort of adults participating in longstanding National Institutes of Health-funded cohort studies.

Association Between Cigarette Smoking and Subclinical Markers of Cardiovascular Harm.

Background: Cigarette smoking is a strong risk factor for cardiovascular harm.

Objectives: The study sought to explore the detailed relationships between smoking intensity, pack-years, and time since cessation with inflammation, thrombosis, and subclinical atherosclerosis markers of cardiovascular harm.

Methods: We included 182,364 participants (mean age 58.

Polygenic Scores of Cardiometabolic Risk Factors in American Indian Adults.

Importance: Numerous efforts have been made to include diverse populations in genetic studies, but American Indian populations are still severely underrepresented. Polygenic scores derived from genetic data have been proposed in clinical care, but how polygenic scores perform in American Indian individuals and whether they can predict disease risk in this population remains unknown.

Objective: To study the performance of polygenic scores for cardiometabolic risk factors of lipid traits and C-reactive protein in American Indian adults and to determine whether such scores are helpful in clinical prediction for cardiometabolic diseases.

Differential Associations of Cigar, Pipe, and Smokeless Tobacco Use Versus Combustible Cigarette Use With Subclinical Markers of Inflammation, Thrombosis, and Atherosclerosis: The Cross-Cohort Collaboration-Tobacco Working Group.

Background: Understanding the associations of tobacco product use with subclinical markers is essential in evaluating health effects to inform regulatory policy. This is particularly relevant for noncigarette products (eg, cigars, pipes, and smokeless tobacco), which have been understudied because of their low prevalence in individual cohorts.

Methods: This cross-sectional study included 98 450 participants from the Cross-Cohort Collaboration-Tobacco data set.

Depression and Incident Hypertension: The Strong Heart Family Study.

Introduction: Compared with White Americans, American Indian adults have disproportionately high depression rates. Previous studies in non-American Indian populations report depression as common among people with uncontrolled hypertension, potentially interfering with blood pressure control. Few studies have examined the association of depressive symptoms with hypertension development among American Indians despite that population's high burden of depression and hypertension.

Cigar, Pipe, and Smokeless Tobacco Use and Cardiovascular Outcomes From Cross Cohort Collaboration.

Importance: Cardiovascular health outcomes associated with noncigarette tobacco products (cigar, pipe, and smokeless tobacco) remain unclear, yet such data are required for evidence-based regulation.

Objective: To investigate the association of noncigarette tobacco products with cardiovascular health outcomes.

Design, Setting, And Participants: This cohort study was conducted within the Cross Cohort Collaboration Tobacco Working Group by harmonizing tobacco-related data and conducting a pooled analysis from 15 US-based prospective cohorts with data on the use of at least 1 noncigarette tobacco product ranging between 1948 and 2015.

Longitudinal lipidomic profiles of left ventricular mass and left ventricular hypertrophy in American Indians.

BACKGROUNDLeft ventricular hypertrophy (LVH) and dyslipidemia are strong, independent predictors for cardiovascular disease, but their relationship is less well studied. A longitudinal lipidomic profiling of left ventricular mass (LVM) and LVH is still lacking.METHODSUsing liquid chromatography-mass spectrometry (LC-MS), we repeatedly measured 1,542 lipids from 1,755 unique American Indians attending 2 exams (mean, 5 years apart).

Admixture Mapping of Chronic Kidney Disease and Risk Factors in Hispanic/Latino Individuals From Central America Country of Origin.

Background: Chronic kidney disease (CKD) is highly prevalent in Central America, and genetic factors may contribute to CKD risk. To understand the influences of genetic admixture on CKD susceptibility, we conducted an admixture mapping screening of CKD traits and risk factors in US Hispanic and Latino individuals from Central America country of origin.

Methods: We analyzed 1023 participants of HCHS/SOL (Hispanic Community Health Study/Study of Latinos) who reported 4 grandparents originating from the same Central America country.

Circulating Sphingolipids and All-Cause Mortality: The Strong Heart Family Study.

Background: A growing body of research indicates that associations of ceramides and sphingomyelins with mortality depend on the chain length of the fatty acid acylated to the backbone sphingoid base. We examined associations of 8 ceramide and sphingomyelin species with mortality among an American Indian population.

Methods And Results: The analysis comprised 2688 participants from the SHFS (Strong Heart Family Study).

Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden.

Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days.

Design, Setting, And Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971.

Genetic variant rs1205 is associated with COVID-19 outcomes: The Strong Heart Study and Strong Heart Family Study.

Background: Although COVID-19 infection has been associated with a number of clinical and environmental risk factors, host genetic variation has also been associated with the incidence and morbidity of infection. The CRP gene codes for a critical component of the innate immune system and CRP variants have been reported associated with infectious disease and vaccination outcomes. We investigated possible associations between COVID-19 outcome and a limited number of candidate gene variants including rs1205.