👤 Martha L Daviglus

The purpose of this study was to estimate the prevalence and number of cerebral microbleeds (CMBs) in a Hispanic and Latino cohort from various self-identified backgrounds and test associations with age, vascular risk factors, APOE (apolipoprotein E), and cognitive function. The 3T brain magnetic resonance imaging exams were obtained on SOL-INCA-MRI (Study of Latinos-Investigation of Neurocognitive Aging-MRI) magnetic resonance imaging study participants, a community-based study. CMB number was counted and categorized as: (1) any CMB, (2) lobar only, (3) deep only, (4) mixed, (5) deep+mixed, and (6) lobar+mixed. We examined whether prevalence of CMBs varied by age, sex, education, Hispanic background, cardiovascular risk factors (hypertension, diabetes, Framingham Risk Score), APOE genotype, and cognition. A total of 2455 participants were included who were 63.0±8.4 years of age, 67.9% women, and 62.2% high school education or higher. CMBs prevalence was 11.7% (8.3% lobar only, 2.0% deep only, 1.4% mixed locations). After adjusting for age, sex, and education, a high Framingham Risk Score was associated with the presence of CMBs of all types, except lobar only. Prevalent stroke/transient ischemic attack was associated with higher likelihood of deep-only CMBs. For participants with cognitive impairment, the adjusted prevalence of mixed CMBs (2.2% versus 1.1%, High vascular risk scores, self-reported history of stroke/transient ischemic attack, and cognitive status were associated with a higher likelihood of CMBs, especially in deep regions. Show less

Apolipoprotein B (apoB) distribution and its implications as an atherosclerotic cardiovascular disease (ASCVD) risk-enhancing factor among individuals of diverse Hispanic or Latino backgrounds have not been described. To describe the distribution of apoB in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort and to characterize associations of baseline sociodemographic and clinical variables with apoB and self-identified Hispanic or Latino background. The HCHS/SOL was a prospective, population-based cohort study of diverse Hispanic or Latino adults living in the US who were recruited and screened between March 2008 and June 2011. Sampling weights were used to generate a population-based sample of Hispanic or Latino participants aged 18 to 74 years who resided in 4 US metropolitan areas (Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California). ApoB concentration was measured in participants from the HCHS/SOL, and apoB tertiles were compared across demographic groups, including self-identified Hispanic or Latino background. Median percentage continental genetic ancestry (West African, Amerindian, and European) was compared across apoB tertiles. ApoB measured in mg/dL from serum or plasma using an immunoturbidimetric assay. ApoB tertiles were determined, and traditional lipids were evaluated across apoB tertiles. ApoB and traditional lipid measurements were assessed across ASCVD risk categories. Additionally, scatterplots were created to observe correlations between apoB and low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol. Overall mean (SD) apoB concentration was 99.8 (0.4) mg/dL, with male participants displaying significantly higher mean levels than female participants (102.4 vs 97.4 mg/dL, respectively). Mean (SD) participant age was 41.1 (0.8) years, and 8376 participants (51.9%) were female. ApoB levels were higher among older age groups. There was significant heterogeneity in mean apoB concentrations across self-identified Hispanic or Latino background groups, ranging from 95.1 mg/dL in Dominican individuals to 104.8 mg/dL in Cuban individuals. The prevalence of elevated apoB (≥130 mg/dL) was greater across higher predicted ASCVD risk categories. Among participants with a 10-year predicted ASCVD risk of 7.5% or higher, 26.5% had an elevated apoB. Median West African ancestry was lower across higher tertiles of apoB. In this cohort study among participants from the HCHS/SOL, elevated apoB was present in one-quarter of a diverse cohort study of Hispanic or Latino individuals who were at intermediate or high predicted ASCVD risk. Differences in apoB distribution among Hispanic or Latino individuals may have important implications for apoB's use in ASCVD risk assessment. Show less

Blood-based biomarkers hold promise as a minimally invasive tool for identifying early signs of Alzheimer's disease pathology and neurodegeneration. We investigated associations between plasma biomarkers of amyloid-beta, tau, neuroaxonal injury, and glial activation with cognitive performance among community-dwelling Hispanic/Latino adults in the United States. We analyzed cross-sectional data from 5730 adults aged 50 years and older (unweighted; mean [SD], 63.5 [8.2] years) in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA; 2016-2018). Plasma concentrations of amyloid-beta (Aβ Here we show higher ln(pTau-181) and ln(NfL) are associated with lower global cognitive performance (b Plasma biomarkers related to Alzheimer's disease pathophysiology and broader neurodegenerative processes are associated with cognitive performance among Hispanic/Latino adults. These findings highlight the potential utility of blood-based biomarkers for identifying early cognitive vulnerability in this population. Show less

Lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease. An Lp(a) threshold of ≥125 nmol/L is commonly used to identify individuals at higher risk for events, but there is a paucity of data on individuals of Hispanic/Latino descent. The purpose of this study was to provide a comprehensive evaluation of Lp(a) and its association with 10-year cardiovascular disease risk and mortality among Hispanic/Latino adults in the United States. We evaluated the association between Lp(a) and myocardial infarction (MI), ischemic stroke, and all-cause mortality among 16,117 Hispanic Community Health Study/Study of Latinos individuals. Event rates were compared across Lp(a) quintiles. Multivariable Cox proportional hazards models assessed the relationship between events and Lp(a) across increasing quintiles, log-transformed Lp(a), and ≥125 nmol/L vs <125 nmol/L. Sampling weights and survey methods were used to account for the stratified probability sampling of the cohort. Among the Hispanic Community Health Study/Study of Latinos target population (median age 41.1 years, 52.4% women), the median Lp(a) was 19.7 nmol/L (Q1-Q3: 7.3-60.6 nmol/L), with 11.4% having Lp(a) ≥125 nmol/L, and the highest Lp(a) quintile defined as >77 nmol/L. Over a median follow-up of 9.8 years, 883 events (135 MI, 99 stroke, 649 all-cause mortality) occurred. The age-adjusted incidence rate of the composite events (MI, stroke, and all-cause mortality) was 505.2 per 100,000 person-years. After multivariable adjustment, each 1-SD increase in log-transformed Lp(a) was associated with a higher risk of MI (HR: 1.47; 95% CI: 1.14-1.89). Compared with Lp(a) <125 nmol/L, elevated Lp(a) ≥125 nmol/L conferred an increased risk of MI (HR: 2.29; 95% CI: 1.45-3.63), all-cause mortality (HR: 1.43; 95% CI: 1.05-1.93), and composite events (HR: 1.56; 95% CI: 1.22-2.01), but not stroke. Findings were consistent when comparing the highest Lp(a) quintile to the lower 4 quintiles, but the elevated risk was observed only for MI and composite events. Hispanic/Latino individuals with elevated Lp(a) are at an increased risk of MI and all-cause mortality. Although Lp(a) ≥125 nmol/L is a valid risk threshold, Hispanics/Latinos show a continuous relationship between increasing Lp(a) levels and MI risk. Show less

Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk. We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data. By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent. Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations. Show less

Over 35% of all adults in the world are currently obese and risk of obesity in racial or ethnic minority groups exist in the US, but the causes of these differences are not all known. As obesity is a leading cause of cardiovascular disease, an improved understanding of risk factors across racial and ethnic groups may improve outcomes. The objective of this study was to determine if susceptibility to obesity is associated with genetic variation in candidate single nucleotide polymorphisms (SNPs) in African Americans and Hispanic/Latinos. We examined data from 534 African Americans and 557 Hispanic/Latinos participants from the UIC Cohort of Patients, Family and Friends. Participants were genotyped for the top 26 obesity-associated SNPs within FTO, MC4R, TUB, APOA2, APOA5, ADIPOQ, ARL15, CDH13, KNG1, LEPR, leptin, and SCG3 genes. The mean (SD) age of participants was 49±13 years, 55% were female, and mean body mass index (BMI) was 31±7.5 kg/m2. After adjusting for age and sex, we found that rs8050136 in FTO (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.1-1.8; P = 0.01) among African Americans and rs2272383 in TUB (OR 1.34, 95% CI 1.04-1.71; P = 0.02) among Hispanic/Latinos were associated with obesity. However, none of the SNPs in multivariable analysis of either AA or H/L cohorts were significant when adjusted for multiple correction. We show that candidate SNPs in the FTO and TUB genes are associated with obesity in African Americans and Hispanic/Latinos individuals respectively. While the underlying pathophysiological mechanisms by which common genetic variants cause obesity remain unclear, we have identified novel therapeutic targets across racial and ethnic groups. Show less