The prevalence, incidence and risk factors of atrial fibrillation (AF) in a large, geographically and ethnically diverse cohort in the United States have not been fully described.
We analyzed data ...from 173,099 participants of the All of Us Research Program recruited in the period 2017-2019, with 92,318 of them having electronic health records (EHR) data available, and 35,483 having completed a medical history survey. Presence of AF at baseline was identified from self-report and EHR records. Incident AF was obtained from EHR. Demographic, anthropometric and clinical risk factors were obtained from questionnaires, baseline physical measurements and EHR.
At enrollment, mean age was 52 years old (range 18-89). Females and males accounted for 61% and 39% respectively. Non-Hispanic Whites accounted for 67% of participants, with non-Hispanic Blacks, non-Hispanic Asians and Hispanics accounting for 26%, 4% and 3% of participants, respectively. Among 92,318 participants with available EHR data, 3,885 (4.2%) had AF at the time of study enrollment, while the corresponding figure among 35,483 with medical history data was 2,084 (5.9%). During a median follow-up of 16 months, 354 new cases of AF were identified among 88,433 eligible participants. Individuals who were older, male, non-Hispanic white, had higher body mass index, or a prior history of heart failure or coronary heart disease had higher prevalence and incidence of AF.
The epidemiology of AF in the All of Us Research Program is similar to that reported in smaller studies with careful phenotyping, highlighting the value of this new resource for the study of AF and, potentially, other cardiovascular diseases.
Abstract People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and ...is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. −10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed.
The public-health impact of cardiovascular disease (CVD) remains high despite advances in prevention and treatment. Large numbers of cardiovascular events occur in asymptomatic people who do not have ...a high level of risk from single risk factors or in terms of multivariable risk scores. Novel risk markers, such as carotid intima-media thickness, high-sensitivity measurement of C-reactive protein, coronary artery calcium score, and genetic risk scores have been suggested as new ways to identify candidates for primary prevention of CVD through intensive risk-factor modification. Yet, many questions remain unanswered. Can these novel markers be used to identify adults who will benefit from statin therapy? How will novel markers affect medication adherence? Is screening using these markers cost-effective? Our opinion is that clinical trials of one or more of these novel tests, combined with monitoring of traditional risk factors, are needed in asymptomatic, low-risk populations.
Targeted prevention of heart failure (HF) remains a critical need given the high prevalence of HF morbidity and mortality. Similar to risk-based prevention of atherosclerotic cardiovascular disease, ...optimal HF prevention strategies should include quantification of risk in the individual patient. In this review, we discuss incorporation of a quantitative risk-based approach into the existing HF staging landscape and the clinical opportunity that exists to translate available data on risk estimation to help guide personalized decision making. We first summarize the recent development of key HF risk prediction tools that can be applied broadly at a population level to estimate risk of incident HF. Next, we provide an in-depth description of the clinical utility of biomarkers to personalize risk estimation in select patients at the highest risk of developing HF. We also discuss integration of genomics-enhanced approaches (eg,
) and other risk-enhancing features to reclassify risk with a precision medicine approach to HF prevention. Although sequential testing is very likely to identify low and high-risk individuals with excellent accuracy, whether or not interventions based on these risk models prevent HF in clinical practice requires prompt attention including randomized placebo-controlled trials of candidate therapies in risk-enriched populations. We conclude with a summary of unanswered questions and gaps in evidence that must be addressed to move the field of HF risk assessment forward.
Background Elevated coronary artery calcium (CAC) is a marker for increase risk of coronary heart disease (CHD). Although most CHD events occur among individuals with advanced CAC, CHD can also occur ...in individuals with little or no calcified plaque. In this study, we sought to evaluate the characteristics associated with incident CHD events in the setting of minimal (score ≤10) or absent CAC (score of zero). Methods Asymptomatic participants in the MESA (N = 6,809) were followed for occurrence of all CHD events (including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death) and hard CHD events (myocardial infarction or CHD death). Time to incident CHD was modeled using age-and gender-adjusted Cox regression. Results The final study population consisted of 3,923 MESA asymptomatic participants (mean age 58 ± 9 years, 39% males) who had CAC scores of 0 to 10. Overall, no detectable CAC was seen in 3415 individuals, whereas 508 had CAC scores of 1 to 10. During follow-up (median 4.1 years), there were 16 incident hard events and 28 all CHD events in individuals with absent or minimal CAC. In age-, gender-, race-, and CHD risk factor-adjusted analysis, minimal CAC (1-10) was associated with an estimated 3-fold greater risk of a hard CHD event (HR 3.23, 95% CI 1.17-8.95) or of all CHD event (HR 3.66, 95% CI 1.71-7.85) compared to those with CAC = 0. Former smoking (HR 3.57, 95% CI 1.08-11.77), current smoking (HR 4.93, 95% CI 1.20-20.30), and diabetes (HR 3.09, 95% CI 1.07-8.93) were significant risk factors for events in those with CAC = 0. Conclusion Asymptomatic persons with absent or minimal CAC are at very low risk of future cardiovascular events. Individuals with minimal CAC (1-10) were significantly increased to 3-fold increased risk for incident CHD events relative to those with CAC scores of zero.
Studies of outpatients with mild or moderate COVID-19 are uncommon. We studied: 1) association of symptoms with reverse transcriptase polymerase chain reaction (RT-PCR) test results; and 2) ...association of initial RT-PCR cycle threshold (Ct) in relation to duration of RT-PCR positivity in outpatients with mild or moderate COVID-19. This was a cohort study of outpatients with confirmed COVID-19 and at least one symptom. Participants had repeat nasopharyngeal swabs and symptom checklists every 3-5 days until two consecutive RT-PCR tests were negative. RT-PCR tests were used to assess viral load. Antibody tests for COVID-19 were performed at 2 weeks, 4 weeks, and 8 weeks after symptom onset. Twenty-five patients (nine females) were enrolled, ranging in age from 19-58 (median age 28 years). All patients reported at least one symptom, with a median of six symptoms per patient. Symptoms persisted for 6-67 days (median duration 18 days). In all 25 patients, blood samples collected a median of 13 days after symptom onset were positive for SARS-CoV-2 antibodies in 15 (60%). After a median of 28 days following symptom onset, 23/23 patients with available samples tested positive for antibodies. The longest duration of positive RT-PCR test was 49 days from first positive PCR test (Mean = 27.4, SD = 12.5, Median = 24). Initial Ct was significantly associated with longer duration (beta = -1.3, SE = 0.3, p<0.01 per 1 cycle higher) of RT-PCR positivity. In mildly or moderately ill COVID-19 outpatients, RT-PCT tests remained positive for as long as 49 days and test positivity and symptom duration correlated with initial viral load.
Background Adverse pregnancy outcomes (APOs) (hypertensive disorders of pregnancy HDP, preterm delivery PTD, or low birth weight LBW) are associated adverse maternal and offspring cardiovascular ...outcomes. Therefore, we sought to describe nationwide temporal trends in the burden of each APO (HDP, PTD, LBW) from 2007 to 2019 to inform strategies to optimize maternal and offspring health outcomes. Methods and Results We performed a serial cross-sectional analysis of APO subtypes (HDP, PTD, LBW) from 2007 to 2019. We included maternal data from all live births that occurred in the United States using the National Center for Health Statistics Natality Files. We quantified age-standardized and age-specific rates of APOs per 1000 live births and their respective mean annual percentage change. All analyses were stratified by self-report of maternal race and ethnicity. Among 51 685 525 live births included, 15% were to non-Hispanic Black individuals, 24% Hispanic individuals, and 6% Asian individuals. Between 2007 and 2019, age standardized HDP rates approximately doubled, from 38.4 (38.2-38.6) to 77.8 (77.5-78.1) per 1000 live births. A significant inflection point was observed in 2014, with an acceleration in the rate of increase of HDP from 2007 to 2014 (+4.1% per year 3.6-4.7) to 2014 to 2019 (+9.1% per year 8.1-10.1). Rates of PTD and LBW increased significantly when co-occurring in the same pregnancy with HDP. Absolute rates of APOs were higher in non-Hispanic Black individuals and in older age groups. However, similar relative increases were seen across all age,racial and ethnic groups. Conclusions In aggregate, APOs now complicate nearly 1 in 5 live births. Incidence of HDP has increased significantly between 2007 and 2019 and contributed to the reversal of favorable trends in PTD and LBW. Similar patterns were observed in all age groups, suggesting that increasing maternal age at pregnancy does not account for these trends. Black-White disparities persisted throughout the study period.
Hypertension, the world's most common and modifiable cardiovascular risk factor, has been the focus of multiple clinical practice guidelines dating back to the first Joint National Committee in 1977. ...In 2014, a writing group commissioned by the National Heart, Lung, and Blood Institute focused on a few key treatment questions and used data only from randomized clinical trials (RCT) to inform their recommendations. Based on a lack of RCT evidence, the writing group recommended relaxing some of the treatment goals for several subgroups, including patients aged 60 years or older and those with diabetes or kidney disease. To address the ensuing controversies and to account for new evidence from recent RCTs that focused on hypertension, the American College of Cardiology and the American Heart Association (ACC/AHA) have now produced the 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. The 2017 ACC/AHA guideline also proposes more aggressive thresholds and goals for treatment relative to prior guidelines.
Metabolic syndrome (MetS) is associated with a history of gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB), but it is unclear whether this association is ...due to the pregnancy complication(s) or prepregnancy/early pregnancy confounders. The study examines the association of GDM, HDP, and PTB with MetS 2-7 years later, independent of early pregnancy factors.
Large, diverse cohort of nulliparous pregnant people with singleton gestations enrolled during their first trimester and who attended a follow-up study visit 2-7 years after delivery. The longitudinal cohort was recruited from eight medical centers across the United States. Using standardized protocols, anthropometry, biospecimens, and surveys were collected at study visits and pregnancy outcomes were abstracted from medical records. We estimated the relative risk of prevalent MetS at the follow-up study visit for participants with GDM, HDP, or PTB (vs. no complications), adjusting for early pregnancy age, body mass index, self-reported race/ethnicity, insurance type, and smoking status.
Of 4,402 participants, 738 (16.8%) had MetS at follow-up: 13.1% (441/3,365) among those with no complications, and 27.9% (290/1,002) among those with complications. MetS occurred in 39.0% of GDM (73/187, adjusted relative risk aRR = 1.75; 95% confidence interval CI 1.42-2.16); 29.2% of HDP (176/603, aRR = 1.49; 95% CI 1.27-1.75); and 29.7% of PTB (113/380, aRR = 1.78; 95% CI 1.49-2.12). Those who had both HDP and PTB (
= 113) had an aRR = 1.95 (95% CI 1.50-2.54).
People whose pregnancies were complicated by GDM, HDP, or PTB are at a higher risk of MetS within 2-7 years after delivery, independent of early pregnancy risk factors. The highest MetS risk follows pregnancies complicated by both HDP and PTB.
Background
Existing equations for prediction of atrial fibrillation (AF) have been developed and validated in white and African‐American populations. Whether these models adequately predict AF in ...more racially and ethnically diverse populations is unknown.
Methods and Results
We studied 6663 men and women 45 to 84 years of age without AF at baseline (2000–2002) enrolled in the Multi‐Ethnic Study of Atherosclerosis (MESA). Of these, 38% were non‐Hispanic whites, 28% non‐Hispanic African Americans, 22% Hispanics, and 12% Chinese Americans. AF during follow‐up was ascertained from hospitalization discharge codes through 2012. Information collected at baseline was used to calculate predicted 5‐year risk of AF using the previously published simple CHARGE‐AF model, which only includes clinical variables, and a biomarker‐enriched CHARGE‐AF model, which also considers levels of circulating N‐terminal of the prohormone B‐type natriuretic peptide and C‐reactive protein. For comparison purposes, we also assessed performance of the 10‐year Framingham AF model. During a mean follow‐up of 10.2 years, 351 cases of AF were identified. The C‐statistic of the CHARGE‐AF models were 0.779 (95% CI, 0.744–0.814) for the simple model and 0.825 (95% CI, 0.791–0.860) for the biomarker‐enriched model. Calibration was adequate in the biomarker‐enriched model (χ2=7.9; P=0.55), but suboptimal in the simple model (χ2=25.6; P=0.002). In contrast, the 10‐year Framingham score had a C‐statistic (95% CI) of 0.746 (0.720–0.771) and showed poor calibration (χ2=57.4; P<0.0001).
Conclusion
The CHARGE‐AF risk models adequately predicted 5‐year AF risk in a large multiethnic cohort. These models could be useful to select high‐risk individuals for AF screening programs or for primary prevention trials in diverse populations.
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