Publications by authors named "David Siscovick"
Introduction: The prevalence of peripheral neuropathy (PN) in the lower limb increases with age and with the presence of diabetes. Studies show an association of PN with advanced cognitive impairment. Here we examine the association of PN with measures of early cognitive deficits in a cohort of older adults without apparent cognitive impairment, with or without diabetes.
View Article and Find Full Text PDFAims: To determine whether discrete lipid profiles (refer to as lipid phenotyping) can be used to stratify cardiovascular risk in individuals with type 2 diabetes.
Methods And Results: Cardiovascular Health Study participants with diabetes and fasting lipid profiles at baseline ( = 866) were categorized separately by level of LDL cholesterol and HDL-C/Triglyceride (Tg) profiles (low Tg/high HDL-C; high Tg/low HDL-C; high Tg only or low HDL-C only). We performed Cox multivariate regression analysis to assess the risk of CVD mortality, incident myocardial infarction (MI), heart failure (HF), stroke, and composite MACE (MI, HF, stroke, and CVD mortality) associated with each lipid category.
Background: Growing evidence indicates that trimethylamine -oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine -oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF).
Methods: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites.
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).
BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.
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- * The research showed that individuals with high polygenic risk scores have significantly higher blood pressure (almost 17 mmHg more) and over seven times the risk of developing hypertension compared to those with low scores.
- * Incorporating these genetic risk scores into hypertension prediction models improved their accuracy, and excitingly, similar genetic associations were found in a large African-American sample, underscoring the potential of these findings for precision health initiatives.
Key Points: In community-based US adults, higher plasma trimethylamine -oxide levels associated with higher risk of incident CKD and greater rate of kidney function decline. Findings from our study support future clinical trials to examine whether lowering plasma trimethylamine -oxide levels may prevent CKD development and progression.
Background: Trimethylamine -oxide (TMAO) is a gut microbiota–derived metabolite of dietary phosphatidylcholine and carnitine.
Background: Gait impairment leads to increased mobility decline and may have neurological contributions. This study explores how neurological biomarkers are related to gait in older adults.
Methods: We studied participants in the Cardiovascular Health Study, a population-based cohort of older Americans, who underwent a serum biomarker assessment from samples collected in 1996-1997 for neurofilament light chain (NfL), glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, and total tau (n = 1 959, mean age = 78.
Background: For the past two decades, the assessment of the quality of diabetes care has mostly relied on clinical quality indicators. These have not included Patient-Reported Outcome Measures (PROMs) which provide information on outcomes deemed valuable by patients. We aimed to examine the potential utility of PROMs in type 2 diabetes care and to study the association of PROMs with patients' characteristics and clinical quality indicators.
View Article and Find Full Text PDFContext: There are no reported data from prospective long-term studies on the relation of androgen levels in young women with development of metabolic syndrome (MetS) before menopause.
Objective: We investigated associations of androgens and SHBG with incident MetS during 23 years of follow-up.
Methods: We included 366 White and 375 Black women ages 20 to 32 years participating in the CARDIA study and CARDIA Women's study, free of MetS at baseline examination (1987-1988), and premenopausal 23 years later.
Article Synopsis
- The study examined the relationship between omega-3 PUFAs and stroke risk across 29 global cohorts, focusing on total, ischemic, and hemorrhagic strokes.
- Results showed that higher levels of eicosapentaenoic acid reduced the incidence of total and ischemic strokes by 17% and 18%, respectively, while docosahexaenoic acid also lowered these risks by 12% and 14%.
- The findings indicate that although higher omega-3 PUFA levels are linked to reduced total and ischemic stroke risks, there is no effect on hemorrhagic strokes.
Aim: Non-esterified fatty acids (NEFA) are potential targets for prevention of key cardiometabolic diseases of aging, but their population-level correlates remain uncertain. We sought to identify modifiable factors associated with fasting and post-load NEFA levels in older adults.
Methods: We used linear regression to determine the cross-sectional associations of demographic, anthropometric, and lifestyle characteristics and medication use with serum fasting and post-load NEFA concentrations amongst community-dwelling older adults enrolled in the Cardiovascular Health Study (n = 1924).
Background: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.
Methods: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed.
Importance: Sphingolipids, including ceramides and sphingomyelins, may influence the pathophysiology and risk of sudden cardiac death (SCD) through multiple biological activities. Whether the length of the fatty acid acylated to plasma sphingolipid species is associated with SCD risk is not known.
Objective: To determine whether the saturated fatty acid length of plasma ceramides and sphingomyelins influences the association with SCD risk.
Introduction: We examined whether a combined measure of neighborhood greenspace and neighborhood median income was associated with white matter hyperintensity (WMH) and ventricle size changes.
Methods: The sample included 1260 cognitively normal ≥ 65-year-olds with two magnetic resonance images (MRI; ≈ 5 years apart). WMH and ventricular size were graded from 0 (least) to 9 (most) abnormal (worsening = increase of ≥1 grade from initial to follow-up MRI scans).
Background: The presence of atrial fibrillation (AF) is associated with an over 2-fold increased risk of stroke, heart failure, and cardiovascular mortality. Long chain n-6 PUFAs have been suggested to have a variety of beneficial biologic effects that may reduce AF development; however, prior studies evaluating this relationship are limited.
Objectives: We prospectively evaluated the association between circulating levels of linoleic acid (LA) and arachidonic acid (AA) with incident AF.
Background: Comprising nearly 35% of brain lipids, polyunsaturated fatty acids (PUFA) are essential for optimal brain function. However, the role of PUFA on cognitive health outcomes later in life is largely unknown.
Objective: We investigated prospective associations of plasma phospholipid omega-3 (ALA [18 : 3], EPA [20 : 5], DPA [22 : 5], DHA [22 : 6]) and omega-6 (LA [18 : 2], AA [20 : 4]) PUFA with cognitive decline, risk of cognitive impairment and dementia among adults aged≥65 years in the Cardiovascular Health Study.
Background: Sphingolipids are a family of circulating lipids with regulatory and signaling roles that are strongly associated with both eGFR and cardiovascular disease. Patients with chronic kidney disease (CKD) are at high risk for cardiovascular events, and have different plasma concentrations of certain plasma sphingolipids compared to patients with normal kidney function. We hypothesize that circulating sphingolipids partially mediate the associations between eGFR and cardiovascular events.
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- Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are important for human health, and previous studies have identified strong genetic signals related to these fats in a specific gene region called FADS among European Americans.
- A new genome-wide association study (GWAS) was conducted with Hispanic American and African American participants to explore genetic signals for n-3 and n-6 PUFAs, confirming the FADS association and finding additional signals nearby in the DAGLA and BEST1 genes.
- Notably, the study discovered unique genetic associations related to arachidonic acid in Hispanic Americans, including a specific genetic variant in the POLD4 gene that is common in this group but absent in others, highlighting the
Background The association of circulating trimethylamine--oxide (TMAO) with stroke has received limited attention. To address this gap, we examined the associations of serial measures of plasma TMAO with incident ischemic stroke. Methods and Results We used a prospective cohort design with data pooled from 2 cohorts.
View Article and Find Full Text PDFBackground: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial.
Objectives: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF.
Methods: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes.