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. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Whole genome sequencing based analysis of inflammation biomarkers in the Trans-Omics for Precision Medicine (TOPMed) consortium.

Inflammation biomarkers can provide valuable insight into the role of inflammatory processes in many diseases and conditions. Sequencing based analyses of such biomarkers can also serve as an exemplar of the genetic architecture of quantitative traits. To evaluate the biological insight, which can be provided by a multi-ancestry, whole-genome based association study, we performed a comprehensive analysis of 21 inflammation biomarkers from up to 38 465 individuals with whole-genome sequencing from the Trans-Omics for Precision Medicine (TOPMed) program (with varying sample size by trait, where the minimum sample size was n = 737 for MMP-1). We identified 22 distinct single-variant associations across 6 traits-E-selectin, intercellular adhesion molecule 1, interleukin-6, lipoprotein-associated phospholipase A2 activity and mass, and P-selectin-that remained significant after conditioning on previously identified associations for these inflammatory biomarkers. We further expanded upon known biomarker associations by pairing the single-variant analysis with a rare variant set-based analysis that further identified 19 significant rare variant set-based associations with 5 traits. These signals were distinct from both significant single variant association signals within TOPMed and genetic signals observed in prior studies, demonstrating the complementary value of performing both single and rare variant analyses when analyzing quantitative traits. We also confirm several previously reported signals from semi-quantitative proteomics platforms. Many of these signals demonstrate the extensive allelic heterogeneity and ancestry-differentiated variant-trait associations common for inflammation biomarkers, a characteristic we hypothesize will be increasingly observed with well-powered, large-scale analyses of complex traits.

Whole Genome Sequencing Based Analysis of Inflammation Biomarkers in the Trans-Omics for Precision Medicine (TOPMed) Consortium.

Inflammation biomarkers can provide valuable insight into the role of inflammatory processes in many diseases and conditions. Sequencing based analyses of such biomarkers can also serve as an exemplar of the genetic architecture of quantitative traits. To evaluate the biological insight, which can be provided by a multi-ancestry, whole-genome based association study, we performed a comprehensive analysis of 21 inflammation biomarkers from up to 38,465 individuals with whole-genome sequencing from the Trans-Omics for Precision Medicine (TOPMed) program. We identified 22 distinct single-variant associations across 6 traits - E-selectin, intercellular adhesion molecule 1, interleukin-6, lipoprotein-associated phospholipase A2 activity and mass, and P-selectin - that remained significant after conditioning on previously identified associations for these inflammatory biomarkers. We further expanded upon known biomarker associations by pairing the single-variant analysis with a rare variant set-based analysis that further identified 19 significant rare variant set-based associations with 5 traits. These signals were distinct from both significant single variant association signals within TOPMed and genetic signals observed in prior studies, demonstrating the complementary value of performing both single and rare variant analyses when analyzing quantitative traits. We also confirm several previously reported signals from semi-quantitative proteomics platforms. Many of these signals demonstrate the extensive allelic heterogeneity and ancestry-differentiated variant-trait associations common for inflammation biomarkers, a characteristic we hypothesize will be increasingly observed with well-powered, large-scale analyses of complex traits.

Optimism and cardiovascular health among African Americans in the Jackson Heart Study.

Little research has examined associations of positive psychosocial factors with the American Heart Association Life's Simple 7™ (LS7) among African Americans. This study examined the associations between positive optimistic orientation and LS7 among African Americans. Using exam 1 data (2000-2004) from the Jackson Heart Study, we examined cross-sectional associations of optimism (in tertiles) with LS7 components [smoking, physical activity, diet, body mass index, blood pressure, cholesterol, glucose] and a composite LS7 score (classified as poor, intermediate, ideal) among 4734 African Americans free of cardiovascular disease. Multivariable prevalence regression was used to estimate prevalence ratios (PR, 95% confidence interval-CI) of intermediate and ideal (vs. poor) individual LS7 components and composite LS7 score by optimism levels, adjusting for demographics, socioeconomic status, and depressive symptoms. For LS7 components with low prevalence, we estimated odds ratios. A greater percentage of participants with high vs. low optimism were younger, female, high SES, and not depressed. After full covariate adjustment, the prevalence ratio of ideal (vs. poor) composite LS7 score was 1.24 for participants who reported high (vs. low) optimism (95% CI 1.09-1.42) at exam 1. Higher levels of optimism were also associated with greater prevalence of ideal (vs. poor) physical activity and smoking. Promoting positive optimistic orientation may be an important step toward increasing the likelihood of achieving optimal cardiovascular health among African Americans.

Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality.

Importance: Cholesterol is a common nutrient in the human diet and eggs are a major source of dietary cholesterol. Whether dietary cholesterol or egg consumption is associated with cardiovascular disease (CVD) and mortality remains controversial. Objective: To determine the associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality. Design, Setting, and Participants: Individual participant data were pooled from 6 prospective US cohorts using data collected between March 25, 1985, and August 31, 2016. Self-reported diet data were harmonized using a standardized protocol. Exposures: Dietary cholesterol (mg/day) or egg consumption (number/day). Main Outcomes and Measures: Hazard ratio (HR) and absolute risk difference (ARD) over the entire follow-up for incident CVD (composite of fatal and nonfatal coronary heart disease, stroke, heart failure, and other CVD deaths) and all-cause mortality, adjusting for demographic, socioeconomic, and behavioral factors. Results: This analysis included 29 615 participants (mean [SD] age, 51.6 [13.5] years at baseline) of whom 13 299 (44.9%) were men and 9204 (31.1%) were black. During a median follow-up of 17.5 years (interquartile range, 13.0-21.7; maximum, 31.3), there were 5400 incident CVD events and 6132 all-cause deaths. The associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality were monotonic (all P values for nonlinear terms, .19-.83). Each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.17 [95% CI, 1.09-1.26]; adjusted ARD, 3.24% [95% CI, 1.39%-5.08%]) and all-cause mortality (adjusted HR, 1.18 [95% CI, 1.10-1.26]; adjusted ARD, 4.43% [95% CI, 2.51%-6.36%]). Each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06 [95% CI, 1.03-1.10]; adjusted ARD, 1.11% [95% CI, 0.32%-1.89%]) and all-cause mortality (adjusted HR, 1.08 [95% CI, 1.04-1.11]; adjusted ARD, 1.93% [95% CI, 1.10%-2.76%]). The associations between egg consumption and incident CVD (adjusted HR, 0.99 [95% CI, 0.93-1.05]; adjusted ARD, -0.47% [95% CI, -1.83% to 0.88%]) and all-cause mortality (adjusted HR, 1.03 [95% CI, 0.97-1.09]; adjusted ARD, 0.71% [95% CI, -0.85% to 2.28%]) were no longer significant after adjusting for dietary cholesterol consumption. Conclusions and Relevance: Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner. These results should be considered in the development of dietary guidelines and updates.

Patterns of Beverages Consumed and Risk of Incident Kidney Disease.

BACKGROUND AND OBJECTIVES: Selected beverages, such as sugar-sweetened beverages, have been reported to influence kidney disease risk, although previous studies have been inconsistent. Further research is necessary to comprehensively evaluate all types of beverages in association with CKD risk to better inform dietary guidelines. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a prospective analysis in the Jackson Heart Study, a cohort of black men and women in Jackson, Mississippi. Beverage intake was assessed using a food frequency questionnaire administered at baseline (2000-2004). Incident CKD was defined as onset of eGFR<60 ml/min per 1.73 m2 and ≥30% eGFR decline at follow-up (2009-13) relative to baseline among those with baseline eGFR ≥60 ml/min per 1.73 m2. Logistic regression was used to estimate the association between the consumption of each individual beverage, beverage patterns, and incident CKD. Beverage patterns were empirically derived using principal components analysis, in which components were created on the basis of the linear combinations of beverages consumed. RESULTS: Among 3003 participants, 185 (6%) developed incident CKD over a median follow-up of 8 years. At baseline, mean age was 54 (SD 12) years, 64% were women, and mean eGFR was 98 (SD 18) ml/min per 1.73 m2. After adjusting for total energy intake, age, sex, education, body mass index, smoking, physical activity, hypertension, diabetes, HDL cholesterol, LDL cholesterol, history of cardiovascular disease, and baseline eGFR, a principal components analysis-derived beverage pattern consisting of higher consumption of soda, sweetened fruit drinks, and water was associated with significantly greater odds of incident CKD (odds ratio tertile 3 versus 1 =1.61; 95% confidence interval, 1.07 to 2.41). CONCLUSIONS: Higher consumption of sugar-sweetened beverages was associated with an elevated risk of subsequent CKD in this community-based cohort of black Americans.

Comparison of Measures of Adiposity and Cardiovascular Disease Risk Factors Among African American Adults: the Jackson Heart Study.

Obesity, particularly central adiposity, is a well-established risk factor for cardiovascular disease (CVD). Waist circumference (WC) is measured in numerous epidemiologic studies as a relatively simple indicator of central adiposity. However, recently, investigators have considered a measure that takes height into consideration, waist-to-height ratio (WHtR) as a more sensitive predictor of CVD. A limited number of studies have examined the association between various measures of central adiposity and obesity with CVD, but there is a dearth of information on this topic focused specifically on African American adults. Given the high rates of cardiovascular disease and metabolic risk factors in this population, it is important to develop validated, easy-to-measure indicators of CVD risk for clinical use. Data from 4758 African American adults participating in the baseline visit of the Jackson Heart Study with available risk factor data were examined, with three measures of body habitus (body mass index (BMI), WC, and WHtR) and five CVD risk factors (HDL and LDL cholesterol, triglycerides, diabetes, and hypertension), the latter also categorized into multiple (2+) risk factors present. C-statistics for waist circumference (WC), BMI, and WHtR were computed and compared for each model to assess their discriminant abilities. WHtR was a stronger correlate of HDL cholesterol, triglycerides, diabetes, hypertension, and multiple risk factors compared to BMI, and was a stronger correlate of HDL cholesterol when compared to WC. These data indicate that, for African American adults, WHtR may be more appropriate measure to identify those at elevated risk for CVD.

Transethnic Evaluation Identifies Low-Frequency Loci Associated With 25-Hydroxyvitamin D Concentrations.

Context: Vitamin D inadequacy is common in the adult population of the United States. Although the genetic determinants underlying vitamin D inadequacy have been studied in people of European ancestry, less is known about populations with Hispanic or African ancestry. Objective: The Trans-Ethnic Evaluation of Vitamin D (TRANSCEN-D) genomewide association study (GWAS) consortium was assembled to replicate genetic associations with 25-hydroxyvitamin D [25(OH)D] concentrations from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) meta-analyses of European ancestry and to identify genetic variants related to vitamin D concentrations in African and Hispanic ancestries. Design: Ancestry-specific (Hispanic and African) and transethnic (Hispanic, African, and European) meta-analyses were performed with Meta-Analysis Helper software (METAL). Patients or Other Participants: In total, 8541 African American and 3485 Hispanic American (from North America) participants from 12 cohorts and 16,124 European participants from SUNLIGHT were included in the study. Main Outcome Measures: Blood concentrations of 25(OH)D were measured for all participants. Results: Ancestry-specific analyses in African and Hispanic Americans replicated single nucleotide polymorphisms (SNPs) in GC (2 and 4 SNPs, respectively). An SNP (rs79666294) near the KIF4B gene was identified in the African American cohort. Transethnic evaluation replicated GC and DHCR7 region SNPs. Additionally, the transethnic analyses revealed SNPs rs719700 and rs1410656 near the ANO6/ARID2 and HTR2A genes, respectively. Conclusions: Ancestry-specific and transethnic GWASs of 25(OH)D confirmed findings in GC and DHCR7 for African and Hispanic American samples and revealed findings near KIF4B, ANO6/ARID2, and HTR2A. The biological mechanisms that link these regions with 25(OH)D metabolism warrant further investigation.

Cardiovascular Disease Burden and Socioeconomic Correlates: Findings From the Jackson Heart Study.

BACKGROUND: Black persons have an excess burden of cardiovascular disease (CVD) compared with white persons. This burden persists after adjustment for socioeconomic status and other known CVD risk factors. This study evaluated the CVD burden and the socioeconomic gradient of CVD among black participants in the JHS (Jackson Heart Study). METHODS AND RESULTS: CVD burden was evaluated by comparing the observed prevalence of myocardial infarction, stroke, and hypertension in the JHS at baseline (2000-2004) with the expected prevalence according to US national surveys during a similar time period. The socioeconomic gradient of CVD was evaluated using logistic regression models. Compared with the national data, the JHS age- and sex-standardized prevalence ratios for myocardial infarction, stroke, and hypertension were 1.07 (95% CI, 0.90-1.27), 1.46 (95% CI, 1.18-1.78), and 1.51 (95% CI, 1.42-1.60), respectively, in men and 1.50 (95% CI, 1.27-1.76), 1.33 (95% CI, 1.12-1.57), and 1.43 (95% CI, 1.37-1.50), respectively, in women. A significant and inverse relationship was observed between socioeconomic status and CVD within the JHS cohort. The strongest and most consistent socioeconomic correlate after adjusting for age and sex was income for myocardial infarction (odds ratio: 3.53; 95% CI, 2.31-5.40) and stroke (odds ratio: 3.73; 95% CI, 2.32-5.97), comparing the poor and affluent income categories. CONCLUSIONS: Except for myocardial infarction in men, CVD burden in the JHS cohort was higher than expected. A strong inverse socioeconomic gradient of CVD was also observed within the JHS cohort.

The American Heart Association Ideal Cardiovascular Health and Incident Type 2 Diabetes Mellitus Among Blacks: The Jackson Heart Study.

BACKGROUND: The concept of ideal cardiovascular health (CVH), defined by the American Heart Association primarily for coronary heart disease and stroke prevention, may apply to diabetes mellitus prevention among blacks. METHODS AND RESULTS: Our sample included 2668 adults in the Jackson Heart Study with complete baseline data on 6 of 7 American Heart Association CVH metrics (body mass index, healthy diet, smoking, total cholesterol, blood pressure, and physical activity). Incident diabetes mellitus was defined as fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes mellitus drugs, or glycosylated hemoglobin ≥6.5%. A summary CVH score from 0 to 6, based on presence/absence of ideal CVH metrics, was derived for each participant. Cox regression was used to estimate adjusted hazard ratios. Mean age was 55 years (65% women) with 492 incident diabetes mellitus events over 7.6 years (24.6 cases/1000 person-years). Three quarters of participants had only 1 or 2 ideal CVH metrics; no participant had all 6. After adjustment for demographic factors (age, sex, education, and income) and high-sensitivity C-reactive protein, each additional ideal CVH metric was associated with a 17% diabetes mellitus risk reduction (hazard ratio, 0.83; 95% CI, 0.74-0.93). The association was attenuated with further adjustment for homeostasis model assessment for insulin resistance (hazard ratio, 0.89; 95% CI, 0.79-1.00). Compared with participants with 1 or no ideal CVH metric, diabetes mellitus risk was 15% and 37% lower in those with 2 and ≥3 ideal CVH metrics, respectively. CONCLUSIONS: The AHA concept of ideal CVH is applicable to diabetes mellitus prevention among blacks. These associations were largely explained by insulin resistance.

Translation of a behavioral weight loss intervention for mid-life, low-income women in local health departments.

OBJECTIVE: To translate a behavioral weight loss intervention for mid-life, low-income women in real world settings. DESIGN AND METHODS: In this pragmatic clinical trial, we randomly selected six North Carolina county health departments and trained their current staff to deliver a 16-session evidence-based behavioral weight loss intervention (special intervention, SI). SI weight loss outcomes were compared to a delayed intervention (DI) control group. RESULTS: Of 432 women expressing interest, 189 completed baseline measures and were randomized within health departments to SI (N = 126) or DI (N = 63). At baseline, average age was 51 years, 53% were African American, mean weight was 100 kg, and BMI averaged 37 kg/m2 . A total of 96 (76%) SI and 55 (87%) DI participants returned for 5-month follow-up measures. The crude weight change was -3.1 kg in the SI and -0.4 kg in the DI group, for a difference of 2.8 kg (95% CI 1.4 to 4.1, p = 0.0001). Diet quality and physical activity improved significantly more in the SI group, and estimated intervention costs were $327 per participant. CONCLUSION: This pragmatic short-term weight loss intervention targeted to low-income mid-life women yielded meaningful weight loss when translated to the county health department setting.

Rationale, design, and sample characteristics of a practical randomized trial to assess a weight loss intervention for low-income women: the Weight-Wise II Program.

Obesity is common among low-income mid-life women, yet most published weight loss studies have not focused on this population and have been highly resourced efficacy trials. Thus, practical type 2 translational studies are needed to evaluate weight loss interventions for low-income women. In this paper, we present the rationale, study design, and baseline characteristics of a type 2 translational study that evaluates both the processes and outcomes of a weight loss intervention for low-income women given at 6 county health departments in North Carolina. Key features of this study include random selection of study sites, intervention delivery by current staff at study sites, efforts to integrate the intervention with local community resources, a focus on evaluating the processes of translation using the RE-AIM framework, use of an evidence-based weight loss intervention, a detailed description of participant recruitment and representativeness, and a practical randomized trial designed to assess the effectiveness of the intervention. Of 81 health departments invited to participate, 30 (37%) were eligible and willing, and 6 were selected at random to deliver the intervention. Of 432 potential participants screened by phone, 213 (49%) were eligible and of these, 189 (89%) completed baseline measures and were randomized to receive a 5-month weight loss intervention or a delayed intervention. The mean age was 51, mean BMI 37 kg/m(2), 53% were African American, and 43% had no health insurance. The results of this study should be informative to key stakeholders interested in real world weight loss interventions for low-income mid-life women.