Blood Pressure on Ambulatory Monitoring and Risk for Cardiovascular Disease and All-cause Mortality: Ecological Validity or Measurement Reliability?

Background: The association with cardiovascular disease (CVD) is stronger for mean systolic blood pressure (SBP) estimated using ambulatory blood pressure monitoring (ABPM) versus office measurements. Determining whether this is due to ABPM providing more measurement reliability or greater ecological validity can inform its use.

Methods: We estimated the association of mean SBP based on 2 office measurements and 2, 5, 10, and 20 measurements on ABPM with incident CVD in the Jackson Heart Study (n=773).

Receipt of antimalarials among children aged 6-59 months in Nigeria from 2010 to 2021.

Background: Nigeria has the highest malaria burden globally, and anti-malarials have been commonly used to treat malaria without parasitological confirmation. In 2012, Nigeria implemented rapid diagnostic tests (RDTs) to reduce the use of anti-malarials for those without malaria and to increase the use of artemisinin-based combination therapy (ACT) for malaria treatment. This study examined changes in anti-malarial receipt among children aged 6-59 months during a 12-year period of increasing RDT availability.

Sex-Associated Metabolites and Incident Stroke, Incident Coronary Heart Disease, Hypertension, and Chronic Kidney Disease in the REGARDS Cohort.

Background: Sex disparities exist in cardiometabolic diseases. Metabolomic profiling offers insight into disease mechanisms, as the metabolome is influenced by environmental and genetic factors. We identified metabolites associated with sex and determined if sex-associated metabolites are associated with incident stoke, incident coronary heart disease, prevalent hypertension, and prevalent chronic kidney disease.

Omega-3 Fatty Acids and Risk of Ischemic Stroke in REGARDS.

We examined associations between lipidomic profiles and incident ischemic stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Plasma lipids (n = 195) were measured from baseline blood samples, and lipids were consolidated into underlying factors using exploratory factor analysis. Cox proportional hazards models were used to test associations between lipid factors and incident stroke, linear regressions to determine associations between dietary intake and lipid factors, and the inverse odds ratio weighting (IORW) approach to test mediation.

Plasma Metabolites and Life's Simple 7 in REGARDS.

Background: The American Heart Association's Life's Simple 7 (LS7) is a health metric that captures important factors associated with cardiovascular and cerebrovascular health. Previous studies highlight the potential of plasma metabolites to serve as a marker for lifestyle and health behavior that could be a target for stroke prevention. The objectives of this study were to identify metabolites that were associated with LS7 and incident ischemic stroke and mediate the relationship between the two.

Trimethylamine N-Oxide and White Matter Hyperintensity Volume Among Patients With Acute Ischemic Stroke.

Importance: Although increasing evidence suggests that trimethylamine N-oxide (TMAO) is associated with atherosclerosis, little is known about whether TMAO and its related metabolites (ie, choline, betaine, and carnitine) are associated with small vessel disease.

Objective: To evaluate the association between TMAO and its related metabolites with features of cerebral small vessel disease, including white matter hyperintensity volume (WMHV) and acute lacunar infarction.

Design, Setting, And Participants: This cross-sectional study included patients enrolled in the Specialized Programs of Translational Research in Acute Stroke biorepository.

Acetylglutamine Differentially Associated with First-Time Versus Recurrent Stroke.

Approximately one-quarter of strokes occur in individuals with prior stroke. Despite the advancement in secondary stroke prevention, the long-term risk of recurrent stroke has remained unchanged. The objective of this study was to identify metabolite risk markers that are associated with recurrent stroke.

Association of Circulating Metabolites With Racial Disparities in Hypertension and Stroke in the REGARDS Study.

Background And Objectives: In the United States, the risk of stroke is greater among Black compared with that among White individuals. However, the reasons for the difference in stroke incidence are not fully elucidated. We aimed to identify metabolites that account for higher prevalent hypertension and incident ischemic stroke among Black adults.

Hypertension severity, apparent treatment resistant hypertension and hyperuricemia in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Background: Prior studies have identified an association between hypertension and hyperuricemia; however, there has been limited research on the association between hypertension severity and hyperuricemia.

Method: We studied 997 Black and white adults with serum urate data from the reasons for geographic and racial differences in stroke (REGARDS) study. Hypertension was defined as SBP ≥ 140 mmHg or DBP ≥ 90 mmHg or self-reported use of antihypertensive medication.

Gut microbiota-associated metabolites and risk of ischemic stroke in REGARDS.

Several metabolite markers are independently associated with incident ischemic stroke. However, prior studies have not accounted for intercorrelated metabolite networks. We used exploratory factor analysis (EFA) to determine if metabolite factors were associated with incident ischemic stroke.

Plasma Metabolites Link Dietary Patterns to Stroke Risk.

Objective: While dietary intake is linked to stroke risk, surrogate markers that could inform personalized dietary interventions are lacking. We identified metabolites associated with diet patterns and incident stroke in a nested cohort from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Methods: Levels of 162 metabolites were measured in baseline plasma from stroke cases (n = 1,198) and random controls (n = 904).

Nucleosides Associated With Incident Ischemic Stroke in the REGARDS and JHS Cohorts.

Background And Objectives: Both genetic and environmental factors contribute to stroke risk. We sought to identify novel metabolites associated with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort and determine whether they reflected genetic or environmental variation.

Methods: This was a stroke case-cohort observational study nested in REGARDS.

PCSK9 loss-of-function variants and risk of infection and sepsis in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

Background: Elevated proprotein convertase subtilisin/kexin type 9 (PCSK9) levels have been associated with adverse outcomes in patients hospitalized for sepsis. PCSK9 loss-of-function (LOF) variants area associated with lower low-density lipoprotein cholesterol (LDL-C) levels. Decreased LDL-C is a biomarker of acute and chronic infection and sepsis risk.

Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium.

Background: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.

Lipid changes due to fenofibrate treatment are not associated with changes in DNA methylation patterns in the GOLDN study.

Fenofibrate lowers triglycerides (TG) and raises high density lipoprotein cholesterol (HDLc) in dyslipidemic individuals. Several studies have shown genetic variability in lipid responses to fenofibrate treatment. It is, however, not known whether epigenetic patterns are also correlated with the changes in lipids due to fenofibrate treatment.

Epigenome-wide association study of fasting measures of glucose, insulin, and HOMA-IR in the Genetics of Lipid Lowering Drugs and Diet Network study.

Known genetic susceptibility loci for type 2 diabetes (T2D) explain only a small proportion of heritable T2D risk. We hypothesize that DNA methylation patterns may contribute to variation in diabetes-related risk factors, and this epigenetic variation across the genome can contribute to the missing heritability in T2D and related metabolic traits. We conducted an epigenome-wide association study for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) among 837 nondiabetic participants in the Genetics of Lipid Lowering Drugs and Diet Network study, divided into discovery (N = 544) and replication (N = 293) stages.