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Biomedical subjects

Karol E Watson

Publications and source records attributed to Karol E Watson.

At least 19 recordsLinked to original sources
PubMed2025

Genetic Variants Associated With the Biochemical Response to Vitamin D3 in the Multi-Ethnic Study of Atherosclerosis.

CONTEXT: The response to treatment with vitamin D varies between patients. OBJECTIVE: To identify genetic variants associated with the biochemical response to vitamin D3 supplementation. DESIGN: Randomized placebo-controlled trial conducted between 2017 and 2019. SETTING: The trial was nested in an ongoing community-based cohort study, the Multi-Ethnic Study of Atherosclerosis. INTERVENTION: 2000 International Units of vitamin D3 or placebo daily for 16 weeks. PARTICIPANTS: The analytic sample included 427 participants assigned to vitamin D3 (mean age, 73 years; 54% females) and was 36% White, 33% Black, 18% Hispanic, and 14% Chinese. MAIN OUTCOME MEASURES: The biochemical response to vitamin D3 included changes in serum concentrations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], PTH, and 25-hydroxyvitamin D3 [25(OH)D3]. RESULTS: In genome-wide analyses, single nucleotide polymorphisms in 8 regions of the genome had significant association (P < 5E-08) with 1 of the traits (2 with change in 1,25(OH)2D3, 1 with change in PTH, and 5 with change in 25(OH)D3). rs16867276 within an intergenic region on 2q31 was associated with change in serum 1,25(OH)2D3 (+8.37&#x2005;pg/mL difference per effect allele; P = 4.93E-08) and was the only locus that achieved genome-wide significance in transethnic meta-analysis. rs114044709 adjacent to FAM20A, which encodes a protein required for biomineralization, was associated with change in PTH among Black participants (+20.32&#x2005;pg/mL difference per effect allele; P = 1.34E-08). In candidate analyses, single nucleotide polymorphisms within SULT2A1 and CYP24A1 had significant association (P < .05&#xf7;36 = .0014) with the changes in 1,25(OH)2D3 and PTH, respectively. CONCLUSION: Our results reveal potential new pathways of vitamin D regulation that require replication in other vitamin D trials.

Humans↗
PubMed2025

Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study.

BACKGROUND: Pulmonary emphysema occurs frequently in older adults, often without airflow limitation. Its presence predicts symptoms, respiratory hospitalizations and deaths, and all-cause mortality. Proteomics may provide further insights into emphysema pathogenesis and inform therapeutic targets. OBJECTIVE: We performed a proteomic discovery analysis of percent emphysema on computed tomography (CT) in a population-based, multiethnic sample from the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study. Replication was performed in two chronic obstructive pulmonary disease (COPD)-based studies, the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) and the Genetic Epidemiology of COPD (COPDGene) Study. METHODS: MESA recruited participants from the general population in 2000-02. The MESA Lung Study performed full-lung CT scans in 2010-12. Percent emphysema was defined as the percentage of lung voxels&#x2009;<&#x2009;-950 Hounsfield units. Over 7,200 plasma aptamers were measured via SomaScan. Cross-sectional linear and least absolute shrinkage and selection operator (LASSO) regression models were adjusted for demographics, anthropometrics, smoking, renal function, and scanner parameters. Statistical significance was defined as a false discovery rate p-value&#x2009;<&#x2009;0.05. Gene Ontology (GO)/Reactome enrichment analyses were performed. LASSO-selected proteins' predictive performance was evaluated. RESULTS: Among 2,504 participants in the MESA Lung Study, mean age was 69.4&#xa0;years, 1,291 had ever smoked, and median percent emphysema-like lung was 1.4%. In total, 1,234 aptamers were significantly associated with percent emphysema in the MESA Lung Study, and 35 replicated in the SPIROMICS and COPDGene Studies. Novel associations included protein family with sequence similarity (FAM) 177A1, syntenin-2, ubiquitin carboxyl-terminal hydrolase 25, and uncharacterized protein C20orf173. Previously identified emphysema-associated proteins included soluble advanced glycosylation end product-specific receptor (sRAGE), protein S100-A12, high mobility group protein B1, and roundabout homolog 2. Enrichment analyses identified 40 GO biological processes, including chemokine production and regulation and cell-cell adhesion and regulation, and two Reactome pathways, including RAGE signaling. In tenfold cross-validation, novel proteins were largely retained by LASSO (R2&#x2009;=&#x2009;5.4%), improved overall model performance (R2&#x2009;=&#x2009;24.8%), and uniquely explained greater variance in percent emphysema. CONCLUSIONS: This analysis in a general population sample identified novel and previously characterized proteins whose functional roles were validated by GO/Reactome enriched pathways, offering new insights into emphysema pathophysiology and therapeutics.

Humans↗
PubMed2005

Comparison of efficacy and safety of rosuvastatin versus atorvastatin in African-American patients in a six-week trial.

The lipid-modifying effects of statin therapy in hypercholesterolemic African-Americans have not been well characterized. This study compared the efficacy and safety of rosuvastatin and atorvastatin treatment for 6 weeks in hypercholesterolemic African-American adults. In the African American Rosuvastatin Investigation of Efficacy and Safety (ARIES) trial (4522US/0002), 774 adult African-Americans with low-density lipoprotein cholesterol > or = 160 and < or = 300 mg/dl and triglycerides < 400 mg/dl were randomized to receive open-label rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg for 6 weeks. At week 6, significantly greater reductions in low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B concentrations, as well as lipoprotein and apolipoprotein ratios, were seen with rosuvastatin versus milligram-equivalent atorvastatin doses (analysis of variance with Bonferroni-adjusted critical p < 0.017 for all comparisons). Rosuvastatin 10 mg also increased high-density lipoprotein cholesterol significantly more than atorvastatin 20 mg (p < 0.017). Although statistical comparisons were not performed, larger proportions of rosuvastatin-treated patients than atorvastatin-treated patients achieved National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. The median high-sensitivity C-reactive protein levels were significantly reduced statistically from baseline with rosuvastatin 20 mg and atorvastatin 20 mg among all patients and with rosuvastatin 10 and 20 mg and atorvastatin 20 mg in those patients with a baseline C-reactive protein level > 2.0 mg/L. The 2 study medications were well tolerated during the 6-week study period. In conclusion, rosuvastatin 10 and 20 mg improved the overall lipid profile of hypercholesterolemic African-Americans better than did milligram-equivalent doses of atorvastatin.

Adult↗
PubMed2005

High-density lipoprotein function recent advances.

Although high-density lipoproteins (HDL) possess many features that contribute to the association between elevated HDL cholesterol and protection from atherosclerosis, these lipoproteins may be modified in certain individuals and/or circumstances to become proinflammatory. The ability of HDL to inhibit or paradoxically to enhance vascular inflammation, lipid oxidation, plaque growth, and thrombosis reflects changes in specific enzyme and protein components. The anti-inflammatory and proinflammatory functional properties of HDL can now be assessed using cell-based and cell-free assays. Acute or chronic systemic inflammation and the metabolic syndrome appear to render HDL proinflammatory. In contrast, statins and experimental agents such as apolipoprotein A-1 mimetics render HDL more anti-inflammatory. Functional characterization of HDL is a promising method for enhanced assessment of cardiovascular risk and effectiveness of risk reduction.

Animals↗
PubMed2005

Opportunity for intervention to achieve American Heart Association guidelines for optimal lipid levels in high-risk women in a managed care setting.

BACKGROUND: The American Heart Association (AHA) recently established evidence-based recommendations for cardiovascular disease (CVD) prevention in women, including lipid management. This study evaluated optimal lipid-level attainment and treatment patterns on the basis of these guidelines in high-risk women in a managed care setting. METHODS AND RESULTS: We conducted a historical prospective cohort analysis of a 1.1-million-member, integrated, managed-care database. Eligible high-risk women were those with evidence of previous CVD or risk equivalent who had a full lipid panel available between October 1, 1999, and September 30, 2000; were naive to lipid therapy; and had a minimum of 12 months health plan eligibility preindex and postindex lipid panel. Optimal lipid levels were defined as LDL cholesterol (LDL-C) <100 mg/dL, HDL cholesterol (HDL-C) >50 mg/dL, non-HDL-C <130 mg/dL, and triglycerides <150 mg/dL. Laboratory values and lipid pharmacotherapy were assessed longitudinally over the postindex follow-up (up to 36 months). A total of 8353 high-risk women (mean age, 66+/-14 years) with a mean follow-up of 27+/-8 months were included. Only 7% attained optimal combined lipid levels initially, and this increased to 12% after 36 months. Lipid-modifying therapy was initiated in 32% of patients, including 35% of women with LDL-C > or =100 mg/dL and 15% with LDL-C <100 mg/dL. CONCLUSIONS: Among high-risk women, few attained the AHA's standards for all lipid fractions, and only one third received recommended drug therapy, highlighting significant opportunities to apply evidence-based recommendations to manage lipid abnormalities in high-risk women.

Adult↗
PubMed2005

The past, present, and future of statin therapy.

Statins are a remarkably safe and efficacious class of medications that have proved to be invaluable in the fight against heart disease. Statins have been prescribed to millions of patients for nearly 20 years; thus there have been hundreds of millions of patient-years of use, with relatively few adverse effects and incalculable benefits. Results from large-scale clinical trials have shown that statins are associated with dramatic decreases in cardiovascular risk. It seems certain that statins will remain a valuable and essential part of the lipid-lowering landscape, but combinations of statins with other lipid-lowering agents are increasingly important. Even with the most potent statins, the desired low-density lipoprotein cholesterol goal might not be attained with statin monotherapy. Furthermore, because of the increasing prevalence of diabetes and the metabolic syndrome, along with their attendant multiple lipid abnormalities, combinations of statins with medications targeted toward multiple lipoprotein particles will emerge.

Cardiovascular Diseases↗
PubMed2004

Pathobiology of atherosclerosis: are there racial and ethnic differences?

Ethnic differences in the prevalence of complex diseases such as atherosclerosis are undoubtedly multifactorial. It is clear that there are social, environmental, biologic, genetic, and other determinants leading to disparities in the rate of coronary heart disease among different ethnic and racial groups. Many epidemiologic studies have characterized the social and environmental factors leading to these differences, but there has been relatively limited investigation of the potential biologic and genetic factors involved. In this review, we will summarize currently available data on ethnic differences in cardiac risk factors, vascular biology, and genetic determinants of atherosclerosis.

Black People↗
PubMed2004

Coronary heart disease care in older women: optimizing diagnostic and therapeutic decisions.

Cardiovascular disease is the leading cause of death and morbidity among women. The prevalence of coronary heart disease (CHD) and its attendant risk clearly increase with advancing age. Though traditionally underrepresented in CHD trials, the proportion of women participating in these studies has risen in recent years. The American Heart Association has recently published statements on the optimal CHD care for both the elderly and female populations. Evidence-based life style and pharmacologic interventions for CHD appear to offer similar benefits in men and women as well as for older patients. However, older women with CHD differ from men in symptoms, the diagnostic performance of cardiac stress tests, the risk of complications from coronary revascularization procedures, and use of proven beneficial therapies. This article synthesizes the current state of the evidence on optimal diagnostic and therapeutic approaches to older women with established CHD.

Aged↗
PubMed2003

Effective strategies for long-term statin use.

Long-term statin use achieves a significant reduction in mortality (24% to 42%) for patients with coronary artery disease (CAD) that is equal to or greater than that seen with other secondary prevention medications, including aspirin, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors. In patients with diabetes, the reduction in mortality exceeds that seen with tight glycemic control or any other treatment for diabetes. Several studies have found that almost all patients with atherosclerosis are considered candidates for statin treatment. The scientific evidence needed to revise the national guidelines has been provided by showing that initiation of statins before hospital discharge results in (1). a marked increase in long-term treatment rates, (2). improved long-term patient compliance, (3). more patients reaching levels of low-density lipoprotein (LDL) cholesterol <100 mg/dL, and (4). improved clinical outcome. Nonetheless, many studies in a variety of clinical settings have demonstrated that, regardless of the health care delivery system, an unacceptable number of patients with atherosclerosis are left untreated or undertreated with statin therapy. Applying hospital-based systems has been demonstrated to address the problems of underuse. The national guidelines now recommend that, in addition to diet and exercise counseling, lipid-lowering medications be initiated before hospital discharge for patients diagnosed with cardiovascular disease. Optimal use of statins and other cardioprotective medications in high-risk patients could save >83000 lives per year in the United States.

Cardiovascular Diseases↗
PubMed2003

Plasma lipoprotein concentrations in ethnic populations.

There is a complex interplay between genetic and environmental factors that influences the expression of plasma lipoprotein levels. It is therefore not surprising that differences in lipid levels have been reported between ethnic groups. There are conflicting data on racial and ethnic variations in lipids, and also limited data on the relationship between lipoprotein levels and coronary heart disease risk in specific populations. This review summarizes available data on ethnic variations in plasma lipoproteins and the potential impact on coronary morbidity and mortality.

Ethnicity↗