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Background: Public health measures necessary to mitigate the spread of coronavirus disease 2019 (COVID-19) impacted lifestyles and health practices. This multiyear cohort analysis of U.S. working-aged adults aims to evaluate the impact of the COVID-19 pandemic on metabolic syndrome and explores contributing factors. Methods: This longitudinal study (n = 19,543) evaluated year-to-year changes in metabolic syndrome and cardiometabolic risk factors through employer-sponsored annual health assessment before and during the COVID-19 pandemic using logistic mixed-effects model. Results: From prepandemic to pandemic (2019 to 2020), prevalence of metabolic syndrome increased by 3.5% for men and 3.0% for women, across all ethnic groups. This change was mainly driven by increased fasting glucose (7.3%) and blood pressure (5.2%). The increased risk of metabolic syndrome was more likely to occur in individuals with an elevated body mass index (BMI) combined with insufficient sleep or physical activity. Conclusions: Cardiometabolic risk increased during the COVID-19 pandemic compared with before the pandemic in a working-aged adult population, more so for those with a high BMI, unhealthy sleep, and low physical activity practices. Given this observation, identification of risk and intervention (including lifestyle and medical) is increasingly necessary to reduce the cardiovascular and metabolic risk, and improve working-aged population health.
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COVID-19 , Enfermedades Cardiovasculares , Síndrome Metabólico , Masculino , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Factores de Riesgo , Pandemias , Estudios Longitudinales , Enfermedades Cardiovasculares/epidemiología , COVID-19/epidemiologíaRESUMEN
Introduction: Strategies to mitigate rising health-care costs are a priority for patients, employers, and health insurers. Yet gaps currently exist in whether health risk assessment can forecast medical claims costs. This study examined the ability of a health quotient (HQ) based on modifiable risk factors, age, sex, and chronic conditions to predict future medical claims spending. Methods: The study included 18,695 employees and adult dependents who participated in health assessments and were enrolled in an employer-sponsored health plan. Linear mixed effect models stratified by chronic conditions and adjusted for age and sex were utilized to evaluate the relationship between the health quotient (score of 0-100) and future medical claims spending. Results: Lower baseline health quotient was associated with higher medical claims cost over 2 years of follow up. For participants with chronic condition(s), costs were $3628 higher for those with a low health quotient (<73; N = 2673) compared to those with high health quotient (>85; N = 1045), after adjustment for age and sex (P value = 0.004). Each one-unit increase in health quotient was associated with a decrease of $154 (95% CI: 87.4, 220.3) in average yearly medical claims costs during follow up. Discussion: This study used a large employee population with 2 years of follow-up data, which provides insights that are applicable to other large employers. Results of this analysis contribute to our ability to predict health-care costs using modifiable aspects of health, objective laboratory testing and chronic condition status.
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OBJECTIVE: Assess whether an employee outreach program improved management of chronic kidney disease (CKD). METHODS: Participants with suspected CKD (eGFR <60 mL/min/1.73m 2 ) identified in employee health assessments in 2017 and 2018 were contacted by phone and offered physician consultation. Subsequent nephrologist visits at 11 months of follow up were compared between those who were (outreach group) and were not (control group) successfully contacted. RESULTS: Most CKD risk factors at baseline were similar in outreach and control groups. At the end of the follow-up, outreach participants had more than 2-fold greater incidence of visiting a nephrologist compared with controls (HR = 2.3; 95% CI 1.2-4.2, P = 0.01), after adjusting for potential confounders. Conclusions: Employee outreach program increased utilization of nephrologist care.
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Insuficiencia Renal Crónica , Lugar de Trabajo , Tasa de Filtración Glomerular , Humanos , Incidencia , Derivación y Consulta , Insuficiencia Renal Crónica/terapia , Factores de RiesgoRESUMEN
In clinical trials, vitamin D supplementation has been reported to reduce serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) but not high-density lipoprotein cholesterol (HDL-C). In this cohort study we evaluated the association between changes in vitamin D (25-hydroxyvitamin D) and changes in lipid levels in a real-world setting. Changes in lipid levels over a 1-year period were evaluated among individuals whose vitamin D levels increased (group 1) or decreased (group 2) by ≥ 10 ng/mL in year 2018 versus 2017 (cohort 1; n = 5580), in 2019 versus 2018 (cohort 2, n = 6057), or in 2020 versus 2019 (cohort 3, n = 7249). In each cohort, levels of TC, LDL-C, and TG decreased in group 1 and increased in group 2. Between-group differences in average changes in the 3 cohorts ranged from 10.71 to 12.02 mg/dL for TC, from 7.42 to 8.95 mg/dL for LDL-C, and from 21.59 to 28.09 mg/dL for TG. These differences were significant after adjusting for age, sex, race, education, body mass index, blood pressure, smoking status, geographical location, and baseline levels of vitamin D and lipids (P < 0.001). Changes in vitamin D levels were not significantly associated with changes in HDL-C levels.
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Biomarcadores/sangre , Lípidos/sangre , Vitamina D/sangre , Vitaminas/sangre , Adulto , Índice de Masa Corporal , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Triglicéridos/sangreRESUMEN
Importance: Low vitamin D levels have been reported to be associated with increased risk of SARS-CoV-2 infection. Independent, well-powered studies could further our understanding of this association. Objective: To examine whether low levels of vitamin D are associated with SARS-CoV-2 seropositivity, an indicator of previous infection. Design, Setting, and Participants: This is a cohort study of employees and spouses who elected to be tested for SARS-CoV-2 IgG as part of an annual employer-sponsored health screening program conducted in August to November 2020. This program includes commonly assessed demographic, biometric, and laboratory variables, including total vitamin D measurement. Baseline (prepandemic) levels of vitamin D and potential confounders were obtained from screening results from the previous year (September 2019 to January 2020). Data analysis was performed from December 2020 to March 2021. Exposures: Low total serum 25-hydroxyvitamin D, defined as either less than 20 ng/mL or less than 30 ng/mL. Main Outcomes and Measures: The main outcome was SARS-CoV-2 seropositivity, as determined with US Food and Drug Administration emergency use-authorized assays. The association of SARS-CoV-2 seropositivity with vitamin D levels was assessed by multivariable logistic regression analyses and propensity score analyses. Results: The 18â¯148 individuals included in this study had test results for SARS-CoV-2 IgG in 2020 and vitamin D levels from the prepandemic and pandemic periods. Their median (interquartile range) age was 47 (37-56) years, 12â¯170 (67.1%) were women, 900 (5.0%) were seropositive, 4498 (24.8%) had a vitamin D level less than 20 ng/mL, and 10â¯876 (59.9%) had a vitamin D level less than 30 ng/mL before the pandemic. In multivariable models adjusting for age, sex, race/ethnicity, education, body mass index, blood pressure, smoking status, and geographical location, SARS-CoV-2 seropositivity was not associated with having a vitamin D level less than 20 ng/mL before (odds ratio [OR], 1.04; 95% CI, 0.88-1.22) or during (OR, 0.93; 95% CI, 0.79-1.09) the pandemic; it was also not associated with having a vitamin D level less than 30 ng/mL before (OR, 1.09; 95% CI, 0.93-1.27) or during (OR, 1.05; 95% CI, 0.91-1.23) the pandemic. Similar results were observed in propensity score analyses. SARS-CoV-2 seropositivity was associated with obesity (OR, 1.26; 95% CI, 1.08-1.46), not having a college degree (OR, 1.40; 95% CI, 1.21-1.62), and Asian (OR, 1.46; 95% CI, 1.13-1.87), Black (OR, 2.74; 95% CI, 2.25-3.34), Hispanic (OR, 2.65; 95% CI, 2.15-3.27), American Indian or Alaska Native, and Native Hawaiian or other Pacific Islander (OR, 2.01; OR, 1.54-2.62) race/ethnicity, and was inversely associated with high blood pressure (OR, 0.82; 95% CI, 0.70-0.96), smoking (OR, 0.60; 95% CI, 0.47-0.78), and residing in the US Northeast (OR, 0.75; 95% CI, 0.62-0.92) and West (OR, 0.54; 95% CI, 0.44-0.67). Conclusions and Relevance: In this cohort study, SARS-CoV-2 seropositivity was not associated with low levels of vitamin D independently of other risk factors.
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COVID-19/sangre , Inmunoglobulina G/sangre , Pandemias , SARS-CoV-2/inmunología , Deficiencia de Vitamina D/sangre , Vitamina D/sangre , Adulto , COVID-19/etiología , COVID-19/virología , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Grupos Raciales , Estudios Retrospectivos , Factores de Riesgo , Deficiencia de Vitamina D/complicacionesRESUMEN
BACKGROUND: The National Comprehensive Cancer Network recommends that women who carry gene variants that confer substantial risk for breast cancer consider risk-reduction strategies, that is, enhanced surveillance (breast magnetic resonance imaging and mammography) or prophylactic surgery. Pathogenic variants can be detected in women with a family history of breast or ovarian cancer syndromes by multigene panel testing. OBJECTIVES: To investigate whether using a seven-gene test to identify women who should consider risk-reduction strategies could cost-effectively increase life expectancy. METHODS: We estimated effectiveness and lifetime costs from a payer perspective for two strategies in two hypothetical cohorts of women (40-year-old and 50-year-old cohorts) who meet the National Comprehensive Cancer Network-defined family history criteria for multigene testing. The two strategies were the usual test strategy for variants in BRCA1 and BRCA2 and the seven-gene test strategy for variants in BRCA1, BRCA2, TP53, PTEN, CDH1, STK11, and PALB2. Women found to have a pathogenic variant were assumed to undergo either prophylactic surgery or enhanced surveillance. RESULTS: The incremental cost-effectiveness ratio for the seven-gene test strategy compared with the BRCA1/2 test strategy was $42,067 per life-year gained or $69,920 per quality-adjusted life-year gained for the 50-year-old cohort and $23,734 per life-year gained or $48,328 per quality-adjusted life-year gained for the 40-year-old cohort. In probabilistic sensitivity analysis, the seven-gene test strategy cost less than $100,000 per life-year gained in 95.7% of the trials for the 50-year-old cohort. CONCLUSIONS: Testing seven breast cancer-associated genes, followed by risk-reduction management, could cost-effectively improve life expectancy for women at risk of hereditary breast cancer.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Detección Precoz del Cáncer/economía , Perfilación de la Expresión Génica/economía , Pruebas Genéticas/economía , Costos de la Atención en Salud , Esperanza de Vida , Años de Vida Ajustados por Calidad de Vida , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/economía , Neoplasias de la Mama/terapia , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Detección Precoz del Cáncer/métodos , Femenino , Predisposición Genética a la Enfermedad , Herencia , Humanos , Imagen por Resonancia Magnética/economía , Mamografía/economía , Mastectomía/economía , Persona de Mediana Edad , Modelos Económicos , Selección de Paciente , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Espera Vigilante/economíaRESUMEN
BACKGROUND: The 2013 ACC/AHA guideline recommended either no statin therapy or moderate-intensity statin therapy (MST) for intermediate risk patients-those with 5-7.5% 10-year risk and without cardiovascular disease (CVD), hypercholesterolemia or diabetes. The guideline further suggested that the therapy choice be based on patient-clinician discussions of risks and benefits. Since low-density lipoprotein particle (LDL-P) levels were reported to be associated with CVD independently of traditional risk factors in intermediate and low risk patients, we investigated the cost-effectiveness of using LDL-P levels to identify intermediate risk patients likely to benefit from initiating or intensifying statin therapy. METHODS: We evaluated 5 care strategies for intermediate risk patients. These included the strategies suggested by the guideline: no-statin therapy and MST. We compared each of these strategies to a related strategy that incorporated LDL-P testing. No-statin therapy was compared with the strategy of MST for those with high LDL-P levels and no statin therapy for all other patients (test-and-MST). MST was compared with the strategy of high-intensity statin therapy (HST) for those with high LDL-P levels and MST for all other patients (test-and-HST). We also evaluated the strategy of HST for all. Costs (payer perspective) and utilities were assessed over a 5-year time horizon in a Markov model of 100,000 hypothetical intermediate risk patients. RESULTS: HST dominated all other strategies, costing less and-despite causing 739 more cases of diabetes than did MST-resulting in more quality adjusted life-years (QALYs). For patient-clinician discussions that would otherwise lead to the MST strategy, we found the test-and-HST strategy reduced costs by $4.67 MM and resulted in 134 fewer CVD events and 115 additional QALYs. For patient-clinician discussions that would otherwise lead to no statin therapy, we found that the test-and-MST strategy reduced costs by $3.25 MM, resulted in 97 fewer CVD events and 44 additional QALYs. CONCLUSIONS: The HST strategy was cost saving and improved outcomes in intermediate risk patients. For patient and clinicians concerned about the adverse events associated with HST, using LDL-P levels to target intensified statin therapy could improve outcomes and reduce costs.
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LDL-Colesterol/sangre , Toma de Decisiones , Predicción , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/economía , Adulto , Anciano , Análisis Costo-Beneficio , Femenino , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Factores de RiesgoRESUMEN
BACKGROUND: Atrial fibrillation (AF) increases risk of stroke, and although this stroke risk can be ameliorated by warfarin therapy, some patients decline to adhere to warfarin therapy. A prospective clinical study could be conducted to determine whether knowledge of genetic risk for AF could increase adherence to warfarin therapy for patients who initially declined therapy. As a prelude to a potential prospective clinical study, we investigated whether the use of genetic information to increase adherence could be cost effective. METHODS: Markov model assessed costs and utilities of two care strategies for AF patients who declined warfarin therapy. In the usual care strategy patients received aspirin. In the test strategy genetic risk for AF was assessed (genotype of the 4q25 locus) and some patients with a positive genetic test (≥1 risk allele) were assumed to adhere to warfarin therapy. The remaining patients received aspirin. The incremental cost-effectiveness ratio (ICER) was the ratio of the costs differential and the quality adjusted life-years (QALYs) differential for the two strategies. RESULTS: We found that the 4q25 genetic testing strategy, compared with the usual care strategy (aspirin therapy), would be cost-effective (ICER $ 47,148) if 2.1 % or more of the test positive patients were to adhere to warfarin therapy. The test strategy would become a cost saving strategy if 5.3 % or more of the test positive patients were to adhere to warfarin therapy. If 20 % of test positive patients were to adhere to warfarin therapy in a hypothetical cohort of 1000 patients, 7 stroke events would be prevented and 3 extra-cranial major bleeding events would be caused over 5 years, resulting in a cost savings of ~ $250,000 and a net gain of 9 QALYs. DISCUSSION: A clinical study to assess the impact of patient knowledge of genetic risk of AF on adherence to warfarin therapy would be merited because even a modest increase in patient adherence would make a genetic testing strategy cost-effective. CONCLUSION: Providing patients who declined warfarin therapy with information about their genetic risk of AF would be cost effective if this genetic risk information resulted in modest increases in adherence.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/genética , Predisposición Genética a la Enfermedad , Cumplimiento de la Medicación , Warfarina/uso terapéutico , Aspirina/uso terapéutico , Análisis Costo-Beneficio , Humanos , Cadenas de Markov , Inhibidores de Agregación Plaquetaria/uso terapéutico , Años de Vida Ajustados por Calidad de VidaRESUMEN
OBJECTIVE: To determine whether a next-generation sequencing (NGS) panel of 34 cancer-associated genes would cost-effectively aid in the treatment selection for patients with metastatic melanoma, compared with a single-site BRAF V600 mutation test. METHODS: A decision model was developed to estimate the costs and health outcomes of the two test strategies. The cost effectiveness of these two strategies was analyzed from a payer perspective over a 2-year time horizon with model parameters taken from the literature. RESULTS: In the base case, the gene sequencing panel strategy resulted in a cost of US$120,022 and 0.721 quality-adjusted life years (QALYs) per patient, whereas the single-site mutation test strategy resulted in a cost of US$128,965 and 0.704 QALYs. Thus, the gene sequencing panel strategy cost US$8943 less per patient and increased QALYs by 0.0174 per patient. Sensitivity analyses showed that, compared with the single-site mutation test strategy, the gene sequencing panel strategy had a 90.9% chance of having reduced costs and increased QALYs, with the cost of the gene sequencing panel test having minimal effect on the incremental cost. CONCLUSION: Compared with the single-site mutation test, the use of an NGS panel of 34 cancer-associated genes as an aid in selecting therapy for patients with metastatic melanoma reduced costs and increased QALYs. If the base-case results were applied to the 8900 patients diagnosed with metastatic melanoma in the USA each year, the gene sequencing panel strategy could result in an annual savings of US$79.6 million and a gain of 155 QALYs.
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Secuenciación de Nucleótidos de Alto Rendimiento/economía , Melanoma/genética , Proteínas Proto-Oncogénicas B-raf/genética , Análisis de Secuencia de ADN/economía , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Predisposición Genética a la Enfermedad , Gastos en Salud , Humanos , Melanoma/economía , Modelos Económicos , Mutación , Metástasis de la Neoplasia , Años de Vida Ajustados por Calidad de Vida , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The prediction of recurrent venous thrombosis using individual genetic risk predictors has proven to be challenging. The aim of this study was to assess whether multiple genetic single nucleotide polymorphism (SNP) analysis would predict recurrent venous thrombosis. METHODS AND RESULTS: Patients with a first venous thrombosis were followed for a recurrent venous thrombosis up to 2009 (MEGA follow-up study), which occurred in 608 out of 4100 patients (2.7%/year). Thirty-one common thrombosis-associated single nucleotide polymorphisms (SNPs) were associated with the risk of recurrence. A genetic risk score (GRS) for each individual was calculated by summing the number of risk-increasing alleles for each of the 31 SNPs and for a simplified model consisting of 5 SNPs: rs6025, rs1799963, rs8176719, rs2066865, and rs2036914. The risk of recurrence associated with the GRS was calculated continuously and after stratification in a low and high score. All individual SNPs were at most mildly associated with recurrence risk. Regarding the 31-SNP GRS, recurrence risk was highest in patients with ≥31 and lowest in patients with <21 risk alleles. The discriminative power of the 5-SNP GRS was similar to that of the 31-SNP GRS. The 6-year cumulative incidence of recurrence was high for individuals with ≥5 (20.3%; 95% confidence interval, 16.5-24.1) and low for individuals with ≤1 (9.4%; 95% confidence interval, 6.7-12.1) risk alleles. Predictive power improved after stratification into provoked and unprovoked first events and sex. CONCLUSIONS: Multiple genetic SNP analysis is useful in the prediction of recurrent thrombosis, even more so when combining this model with clinical risk factors.
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Variación Genética , Trombosis de la Vena/genética , Adolescente , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Modelos de Riesgos Proporcionales , Recurrencia , Factores de Riesgo , Trombosis de la Vena/epidemiología , Trombosis de la Vena/patología , Adulto JovenRESUMEN
BACKGROUND: Results from the PROVE IT trial suggest that patients with acute coronary syndrome (ACS) treated with atorvastatin 80 mg/day (A80) have significantly lower rates of cardiovascular events compared with patients treated with pravastatin 40 mg/day (P40). In a genetic post hoc substudy of the PROVE IT trial, the rate of event reduction was greater in carriers of the Trp719Arg variant in kinesin family member 6 protein (KIF6) than in noncarriers. We assessed the cost effectiveness of testing for the KIF6 variant followed by targeted statin therapy (KIF6 Testing) versus not testing patients (No Test) and treating them with P40 or A80 in the USA from a payer perspective. METHODS: A Markov model was developed in which 2-year event rates from PROVE IT were extrapolated over a lifetime horizon. Costs and utilities were derived from published literature. All costs were in 2010 US dollars except the cost of A80, which was in 2012 US dollars because the generic formulation was available in 2012. Expected costs and quality-adjusted life-years (QALYs) were estimated for each strategy over a lifetime horizon. RESULTS: Lifetime costs were US$31,700; US$37,100 and US$41,300 for No Test P40, KIF6 Testing and No Test A80 strategies, respectively. The No Test A80 strategy was associated with more QALYs (9.71) than the KIF6 Testing (9.69) and No Test P40 (9.57) strategies. No Test A80 had an incremental cost-effectiveness ratio (ICER) of US$232,100 per QALY gained compared with KIF6 Testing. KIF6 Testing had an ICER of US$45,300 per QALY compared with No Test P40. CONCLUSIONS: Testing ACS patients for KIF6 carrier status may be a cost-effective strategy at commonly accepted thresholds. Treating all patients with A80 is more expensive than treating patients on the basis of KIF6 results, but the modest gain in QALYs is achieved at a cost/QALY that is generally considered unacceptable compared with the KIF6 Testing strategy. Compared with treating all patients with P40, the KIF6 Testing strategy had an ICER below US$50,000 per QALY. The conclusions from this study are sensitive to the price of generic A80 and the effect on adherence of knowing KIF6 carrier status. The results were based on a post hoc substudy of the PROVE IT trial, which was not designed to test the effectiveness of KIF6 testing.
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Síndrome Coronario Agudo/tratamiento farmacológico , Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Cinesinas/genética , Pirroles/uso terapéutico , Síndrome Coronario Agudo/economía , Síndrome Coronario Agudo/genética , Atorvastatina , Análisis Costo-Beneficio , Relación Dosis-Respuesta a Droga , Femenino , Pruebas Genéticas/economía , Pruebas Genéticas/métodos , Genotipo , Ácidos Heptanoicos/economía , Ácidos Heptanoicos/farmacología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/economía , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Masculino , Cadenas de Markov , Persona de Mediana Edad , Terapia Molecular Dirigida , Pravastatina/administración & dosificación , Pravastatina/economía , Pravastatina/uso terapéutico , Pirroles/economía , Pirroles/farmacología , Años de Vida Ajustados por Calidad de VidaRESUMEN
OBJECTIVE: Preeclampsia has been linked to subsequent vascular disease with many shared predisposing factors. We investigated the association between severe preeclampsia, and its subtypes, and specific vascular-related polymorphisms. DESIGN: The study was a retrospective nested case-cohort design. SETTING: Pregnant Danish women participating in the Danish National Birth Cohort. Population. 263 cases of severe preeclampsia and 1851 random controls were selected from the Danish National Birth Cohort. METHODS: We validated all cases of severe preeclampsia and genotyped for 108 single nucleotide polymorphisms (SNPs) that were selected based on previous publications on the association with vascular disease. Logistic models were used for statistical analyses. MAIN OUTCOME MEASURES: Maternal polymorphisms in genomic models. RESULTS: We found 17 of 108 SNPs associated with severe preeclampsia (p < 0.05). Women homozygous for the rs1799983 in NOS3 were 1.6-fold [95% confidence interval (CI) 1.0-2.4] more likely to develop severe preeclampsia. Women homozygous for the rs1010 SNP in VAMP8 were twofold (95%CI 1.1-3.5) more likely to deliver preterm when preeclampsia was present. Women homozygous for the rs10811661 SNP were 2.1-fold (95%CI 1.1-3.9) more likely to develop severe preeclampsia and 3.7-fold (95%CI 1.1-12.4) more likely to deliver a small-for-gestational age child when preeclampsia was present. All associations are available as Supporting Information. CONCLUSION: We found several vascular-associated SNPs linked to severe preeclampsia; however, most of these associations are probably by pure chance, which warrants replication and further translational research. To date, no specific SNP has yet proven valuable in a clinical setting in predicting preeclampsia.
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Polimorfismo de Nucleótido Simple , Preeclampsia/epidemiología , Preeclampsia/genética , Adulto , Distribución por Edad , Peso al Nacer , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Genotipo , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Oportunidad Relativa , Paridad , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Factores SocioeconómicosRESUMEN
There are no risk models available yet that accurately predict a person's risk for developing venous thrombosis. Our aim was therefore to explore whether inclusion of established thrombosis-associated single nucleotide polymorphisms (SNPs) in a venous thrombosis risk model improves the risk prediction. We calculated genetic risk scores by counting risk-increasing alleles from 31 venous thrombosis-associated SNPs for subjects of a large case-control study, including 2712 patients and 4634 controls (Multiple Environmental and Genetic Assessment). Genetic risk scores based on all 31 SNPs or on the 5 most strongly associated SNPs performed similarly (areas under receiver-operating characteristic curves [AUCs] of 0.70 and 0.69, respectively). For the 5-SNP risk score, the odds ratios for venous thrombosis ranged from 0.37 (95% confidence interval [CI], 0.25-0.53) for persons with 0 risk alleles to 7.48 (95% CI, 4.49-12.46) for persons with more than or equal to 6 risk alleles. The AUC of a risk model based on known nongenetic risk factors was 0.77 (95% CI, 0.76-0.78). Combining the nongenetic and genetic risk models improved the AUC to 0.82 (95% CI, 0.81-0.83), indicating good diagnostic accuracy. To become clinically useful, subgroups of high-risk persons must be identified in whom genetic profiling will also be cost-effective.
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Predisposición Genética a la Enfermedad/epidemiología , Pruebas Genéticas/métodos , Polimorfismo de Nucleótido Simple/genética , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/genética , Análisis Costo-Beneficio , Femenino , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas/economía , Pruebas Genéticas/normas , Humanos , Masculino , Modelos Genéticos , Modelos Estadísticos , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
A single nucleotide polymorphism (SNP) in KIF6, a member of the KIF9 family of kinesins, is associated with differential coronary event reduction from statin therapy in four randomized controlled trials; this SNP (rs20455) is also associated with the risk for coronary heart disease (CHD) in multiple prospective studies. We investigated whether other common SNPs in the KIF6 region were associated with event reduction from statin therapy. Of the 170 SNPs in the KIF6 region investigated in the Cholesterol and Recurrent Events trial (CARE), 28 were associated with differential event reduction from statin therapy (P (interaction) < 01 in Caucasians, adjusted for age and sex) and were further investigated in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI22) and West of Scotland Coronary Prevention Study (WOSCOPS). These analyses revealed that two SNPs (rs9462535 and rs9471077), in addition to rs20455, were associated with event reduction from statin therapy (P (interaction) < 0.1 in each of the three studies). The relative risk reduction ranged from 37 to 50% (P < 0.01) in carriers of the minor alleles of these SNPs and from -4 to 13% (P > 0.4) in non-carriers. These three SNPs are in high linkage disequilibrium with one another (r (2) > 0.84). Functional studies of these variants may help to understand the role of KIF6 in the pathogenesis of CHD and differential response to statin therapy.
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Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/genética , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Cinesinas/genética , Polimorfismo de Nucleótido Simple , Mapeo Cromosómico , Enfermedad Coronaria/prevención & control , Femenino , Humanos , Desequilibrio de Ligamiento , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND AND METHODOLOGY: The 719Arg allele of KIF6 (rs20455) was associated with coronary events in Caucasian participants of five prospective studies. We investigated whether this KIF6 variant was associated with non-fatal myocardial infarction (MI) in a case-control study of an admixed population from the Central Valley of Costa Rica. Genotypes of the KIF6 variant were determined for 4,134 men and women. Cases (1,987) had survived a first MI; controls (2,147) had no history of MI and were matched to cases by age, sex, and area of residence. We tested the association between the KIF6 719Arg allele and non-fatal MI by conditional logistic regression and adjusted for admixture of founder populations. PRINCIPAL FINDINGS: Compared with the reference Trp/Trp homozygotes, KIF6 719Arg carriers were not at significantly higher risk for non-fatal MI in this study after adjustment for traditional risk factors or admixture (OR= 1.12; 95%CI, 0.98-1.28). Heterozygotes of the KIF6 Trp719Arg variant were at increased risk of non-fatal MI: the adjusted odds ratio was 1.16 (95% confidence interval, 1.01-1.34), but this association would not be significant after a multiple testing correction. CONCLUSIONS/SIGNIFICANCE: We found that carriers of the KIF6 719Arg allele were not at increased risk of non-fatal MI in a case-control study of Costa Ricans living in the Central Valley of Costa Rica.
Asunto(s)
Cinesinas/genética , Mutación Missense , Infarto del Miocardio/genética , Adulto , Anciano , Estudios de Casos y Controles , Costa Rica/epidemiología , Femenino , Genotipo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: We recently reported the association between the Malmö sequence variant in F9 (rs6048) and deep vein thrombosis. DESIGN AND METHODS: We aimed to study whether the association between F9 Malmö and deep vein thrombosis is explained by linkage disequilibrium with nearby single-nucleotide polymorphisms, and whether the association is explained biologically by F9 Malmö affecting factor IX antigen levels or activation of factor IX. We investigated the association of F9 Malmö and 28 nearby single-nucleotide polymorphisms with deep vein thrombosis in men from two case-control studies, LETS (n=380) and MEGA (n=1,469). We assessed the association of F9 Malmö with factor IX antigen level in male control subjects from LETS (n=191) and two subsets of MEGA (n=823 and n=484) and the association with endogenous thrombin potential in LETS control men. We studied the association between F9 Malmö and factor IX activation peptide in 1,199 healthy middle-aged men from the NPHS-II cohort. RESULTS: In the combined LETS and MEGA studies, the odds ratio (95% confidence interval) for the G allele of F9 Malmö, compared with the A allele, was 0.80 (0.69-0.93). One single-nucleotide polymorphism in F9, rs422187, was strongly linked to F9 Malmö (r(2)=0.94) and was similarly associated with deep vein thrombosis. No other single-nucleotide polymorphism or haplotype tested was more strongly associated. Factor IX antigen level, factor IX activation peptide levels and endogenous thrombin potential did not differ between F9 Malmö genotypes. CONCLUSIONS: The F9 Malmö sequence variant was the most strongly associated with deep vein thrombosis among common single-nucleotide polymorphisms in the region. However, the biological mechanism by which F9 Malmö affects risk remains unknown.
Asunto(s)
Factor IX/genética , Polimorfismo de Nucleótido Simple , Trombosis de la Vena/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Cromosomas Humanos X/genética , Factor IX/metabolismo , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Trombosis de la Vena/sangre , Adulto JovenRESUMEN
BACKGROUND: Hypertension is a risk factor for coronary heart disease (CHD), but the causes of hypertension remain largely unknown. Genetic variation is thought to contribute to the etiology of hypertension. We tested a single-nucleotide polymorphism (SNP) (Lys67Arg, rs197922) in the Golgi SNAP Receptor Complex Member 2 (GOSR2) gene for association with hypertension and blood pressure (BP). We chose this SNP because it was nominally associated with CHD in earlier studies. Further, GOSR2 is located in a linkage region for hypertension and BP in human and animal studies. METHODS: We used logistic and linear regression to test associations of the GOSR2 SNP with hypertension and BP among 3,528 blacks and 9,861 whites from the Atherosclerosis Risk in Communities (ARIC) study. Race-specific regression models of hypertension were adjusted for age and gender. Regression models of BP were further adjusted for antihypertensive medication use. RESULTS: The GOSR2 Lys67 allele was associated with hypertension in whites (odds ratio (OR) = 1.09, P = 0.01) but not blacks (OR = 0.96, P = 0.47). The Lys67 allele was associated with increased systolic BP (SBP) in both races (0.87 mm Hg, P < 0.001 among whites and 1.05 mm Hg, P = 0.05 among blacks). A similar association in whites was observed for the GOSR2 SNP and SBP in the Women's Genome Health Study (WGHS) (OR = 1.03, P = 0.04). The OR remained unchanged after adjustment for antihypertensive medication use (OR = 1.03, P = 0.11), though it was no longer statistically significant. CONCLUSIONS: We found evidence that a SNP in GOSR2 is modestly associated with hypertension in whites from the ARIC study and the WGHS.