Association of changes in lipid levels with changes in vitamin D levels in a real-world setting.

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.

Assessment of the Association of Vitamin D Level With SARS-CoV-2 Seropositivity Among Working-Age Adults.

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 18 148 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, 12 170 (67.1%) were women, 900 (5.0%) were seropositive, 4498 (24.8%) had a vitamin D level less than 20 ng/mL, and 10 876 (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.

Concordance of Cardiovascular Risk Factors and Behaviors in a Multiethnic US Nationwide Cohort of Married Couples and Domestic Partners.

Importance: Married couples and domestic partners have been reported to share similar environmental exposures, adopt similar behavior patterns, and have similar transferable characteristics. However, the degree to which couples share similar levels of cardiovascular risk factors and behaviors is uncertain. Objective: To assess within-couple concordance of the American Heart Association-defined Life's Simple 7 (LS7). Design, Setting, and Participants: Cross-sectional study with a longitudinal substudy of employees and spouses (or domestic partners) who participated in an employer-sponsored health assessment program throughout the United States between October 2014 and December 2018. Data were analyzed from November 1, 2019, to August 4, 2020. Exposures: Having a spouse or domestic partner. Main Outcomes and Measures: The LS7 risk factors and behaviors (smoking status, body mass index, exercise, diet, total cholesterol, blood pressure, and fasting glucose) were assessed by questionnaires, examinations, and laboratory tests. LS7 categories were scored as 2 for ideal, 1 for intermediate, or 0 for poor and summed to generate a CV health score. Results: The study included 10 728 participants (5364 couples): 7% were African American, 11% Hispanic, 21% Asian, and 54% White (median [interquartile range] age, 50 [41-57] years for men and 47 [39-55] for women). For most couples, both members were in the ideal category or both were in a nonideal category. Concordance ranged from 53% (95% CI, 52%-54%) for cholesterol to 95% (95% CI, 94%-95%) for diet. For the CV health score, in 79% (95% CI, 78%-80%) of couples both members were in a nonideal category, which was associated mainly with unhealthy diet (94% [95% CI, 93%-94%] of couples) and inadequate exercise (53% [95% CI, 52%-55%] of couples). However, in most couples, both members were in the ideal category for smoking status (60% [95% CI, 59%-61%] of couples) and glucose (56% [95% CI, 55%-58%]). Except for total cholesterol, when 1 member of a couple was in the ideal category, the other member was likely also to be in the ideal category: the adjusted odds ratios for also being in the ideal category ranged from 1.3 (95% CI, 1.1-1.5; P ≤ .001) for blood pressure to 10.6 (95% CI, 7.4-15.3; P ≤ .001) for diet. Concordance differed by ethnicity, socioeconomic status, and geographic location. A 5-year longitudinal analysis of 2186 couples found modest changes in concordance of blood pressure (from 55% [95% CI, 53%-57%] to 59% [95% CI, 57%-61%]; P < .001 for trend) and fasting glucose (from 64% [95% CI, 62%-66%] to 59% [95% CI, 57%-61%]; P < .001 for trend) with no change in other factors. Conclusions and Relevance: In this study, high concordance of nonideal behaviors was found within couples; behavioral modification programs may benefit both the targeted and the nontargeted member of a couple.

Cost-effectiveness of nucleic acid amplification testing to guide treatment for vaginitis: a decision-modeling analysis.

We evaluated the cost-effectiveness of test-and-treat scenarios for vaginitis, scenarios based on clinical and microscopic examination (CME), nucleic acid amplification testing (NAAT), or nonamplified nucleic acid probe (probe) testing. The symptom resolution outcome and the payer cost of diagnosis and treatment were estimated in decision analytical models in a hypothetical patient population. Compared with probe testing, NAAT resulted in symptom resolution in more patients (615 versus 475 per 1000 tested) at a cost of $210 per incremental symptom resolution, a cost lower than the willingness to pay for symptom resolution ($871) implied by payer coverage for probe testing. Following a negative CME, the NAAT scenario resulted in symptom resolution in more patients (650 per 1000 patients tested) than did either CME (525) or the CME probe testing-based scenario (602) at incremental cost-effectiveness ratios lower than the willingness to pay implied by coverage for CME. Therefore, NAAT is likely to cost-effectively improve health outcomes for patients with vaginitis.

Gaps in Dyslipidemia Care Among Working-Aged Individuals With Employer-Sponsored Health Care.

Background The American Heart Association and American College of Cardiology guidelines defined patient-management groups that would benefit from lowering of low-density lipoprotein cholesterol (LDL-C). We assessed gaps in dyslipidemia care among employees and spouses with health benefits. Methods and Results We studied 17 889 employees and spouses who were covered by an employer-sponsored health plan and participated in an annual health assessment. Using medical claims, laboratory tests, and risk assessment questionnaires, we found that 43% of participants were in one of 4 patient-management groups: secondary prevention, severe hypercholesterolemia (LDL-C ≥190 mg/dL at least once in the preceding 5 years), diabetes mellitus, or elevated 10-year risk of cardiovascular disease. To assess gaps in dyslipidemia care, we used LDL-C ≤70 mg/dL as the goal for both the secondary prevention group and those in the elevated 10-year risk group with >20% risk; LDL-C ≤100 mg/dL was used for the other groups. Among those in patient-management groups, 27.3% were in the secondary prevention group, 7.4% were in the severe hypercholesterolemia group, 29.9% were in the diabetes mellitus group, and 35.4% were in the elevated 10-year risk group. About 74% of those in patient-management groups had above-goal LDL-C levels, whereas only 31% had evidence of a lipid-lowering therapy in the past 6 months: 45% in the secondary prevention group, 31% in the severe hypercholesterolemia group, 36% in the diabetes mellitus group, and 17% in the elevated 10-year risk group. Conclusions The substantial gaps in LDL-C treatment and goal attainment among members of an employer-sponsored medical plan who were mostly aware of their LDL-C levels indicate the need for gap-closure initiatives.

Outreach and Connection to Care for Chronic Kidney Disease in a Workplace Wellness Setting: A Cost-Effectiveness Analysis.

Because chronic kidney disease (CKD) is underdiagnosed, many patients do not receive care that could slow or prevent progression. Potential CKD patients can be identified during employee wellness events and referred into care by a CKD outreach program. This study assessed the health and economic benefits associated with a CKD outreach program. A model-based cost-effectiveness analysis was conducted for a cohort of patients at risk for CKD under 2 scenarios: wellness events with a CKD outreach program and wellness events without outreach. The outreach program identified potential CKD patients based on estimated glomerular filtration rates. Health outcomes and total cost to payers were estimated with Markov models using 1-year cycles. Because outreach could be offered to either patients with diabetes or to all potential CKD patients, these groups were modeled separately. The authors assumed 40% percent of potential CKD patients accepted the invitation to participate in the CKD outreach program. Model parameters were taken from peer-reviewed literature. The study was conducted from the perspective of self-insured employers over a 5-year time horizon. The study found that the CKD outreach program resulted in a gain of 2.3 quality-adjusted life-years and saved $500,211 when 1000 potential CKD patients with diabetes were invited. When potential CKD patients were invited without regard for diabetes status, 0.8 quality-adjusted life-years were gained at a cost savings of $34,161. The authors concluded that CKD outreach programs can improve health outcomes for patients with CKD and save costs for payers.

Insulin Resistance Probability Scores for Apparently Healthy Individuals.

CONTEXT: Insulin resistance (IR) can progress to type 2 diabetes. Therefore, timely identification of IR could facilitate disease prevention efforts. However, direct measurement of IR is not feasible in a clinical setting. OBJECTIVE: Develop a clinically practical probability score to assess IR in apparently healthy individuals based on levels of insulin, C-peptide, and other risk factors. DESIGN: Cross-sectional study. PARTICIPANTS: Apparently healthy individuals who volunteered to participate in studies of IR. MAIN OUTCOME MEASURE: IR, defined as the top tertile of steady-state plasma glucose during an insulin-suppression test. RESULTS: In a study of 535 participants, insulin, C-peptide, creatinine, body mass index (BMI), and triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) were independently associated with IR (all P < 0.05) in a model that included age, sex, ethnicity, BMI, blood pressure, insulin, C-peptide, fasting glucose, low-density lipoprotein cholesterol, TG/HDL-C, alanine aminotransferase, and creatinine. For an IR probability score based on a model that included insulin, C-peptide, creatinine, TG/HDL-C, and BMI, the odds ratio was 26.7 (95% CI 14.0 to 50.8) for those with scores >66% compared with those with scores <33%. When only insulin and C-peptide were included in the model, the odds ratio was 15.6 (95% CI 7.5 to 32.4) for those with scores >66% compared with those with scores <33%. CONCLUSIONS: An IR probability score based on insulin, C-peptide, creatinine, TG/HDL-C, and BMI or a score based on only insulin and C-peptide may help assess IR in apparently healthy individuals.

Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF. METHODS AND FINDINGS: Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF. CONCLUSIONS: Prospective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01970969.

Cost Effectiveness of Karyotyping, Chromosomal Microarray Analysis, and Targeted Next-Generation Sequencing of Patients with Unexplained Global Developmental Delay or Intellectual Disability.

BACKGROUND: Genetic diagnosis of unexplained global developmental delay and intellectual disability (GDD/ID) often ends the diagnostic odyssey and can lead to changes in clinical management. OBJECTIVE: The objective of this study was to investigate the cost effectiveness of testing scenarios involving several methods used to diagnose GDD/ID: karyotyping, chromosomal microarray analysis (CMA), and targeted next-generation sequencing (NGS). METHODS: We used decision-tree models to estimate the number of genetic diagnoses, the cost from a payers' perspective in the USA, and the incremental cost per additional genetic diagnosis. Model parameters were taken from peer-reviewed literature and governmental fee schedules. RESULTS: CMA testing results in more genetic diagnoses at an incremental cost of US $2692 per additional diagnosis compared with karyotyping, which has an average cost per diagnosis of US $11,033. Performing both tests sequentially results in the same number of diagnoses, but the total cost is less when CMA testing is done first and karyotyping second. Furthermore, when CMA testing yields a variant of unknown significance, additional genetic diagnoses can be obtained at an incremental cost of US $4220 by CMA testing of both parents, and when parents are not available or the patient had a normal CMA result, targeted NGS of the patient can add diagnoses at a further incremental cost of US $12,295. CONCLUSION: These results provide a cost effectiveness rationale for the use of CMA as the first-tier test for the genetic diagnosis of unexplained GDD/ID and further indicate that testing of both parents may be cost effective when a variant of unknown significance is detected in the patient.

Prediction of Type 2 Diabetes by Hemoglobin A1c in Two Community-Based Cohorts.

OBJECTIVE: Hemoglobin A1c (HbA1c) can be used to assess type 2 diabetes (T2D) risk. We asked whether HbA1c was associated with T2D risk in four scenarios of clinical information availability: 1) HbA1c alone, 2) fasting laboratory tests, 3) clinic data, and 4) fasting laboratory tests and clinic data. RESEARCH DESIGN AND METHODS: We studied a prospective cohort of white (N = 11,244) and black (N = 2,294) middle-aged participants without diabetes in the Framingham Heart Study and Atherosclerosis Risk in Communities study. Association of HbA1c with incident T2D (defined by medication use or fasting glucose [FG] ≥126 mg/dL) was evaluated in regression models adjusted for 1) age and sex (demographics); 2) demographics, FG, HDL, and triglycerides; 3) demographics, BMI, blood pressure, and T2D family history; or 4) all preceding covariates. We combined results from cohort and race analyses by random-effects meta-analyses. Subsidiary analyses tested the association of HbA1c with developing T2D within 8 years or only after 8 years. RESULTS: Over 20 years, 3,315 individuals developed T2D. With adjustment for demographics, the odds of T2D increased fourfold for each percentage-unit increase in HbA1c. The odds ratio (OR) was 4.00 (95% CI 3.14, 5.10) for blacks and 4.73 (3.10, 7.21) for whites, resulting in a combined OR of 4.50 (3.35, 6.03). After adjustment for fasting laboratory tests and clinic data, the combined OR was 2.68 (2.15, 3.34) over 20 years, 5.79 (2.51, 13.36) within 8 years, and 2.23 (1.94, 2.57) after 8 years. CONCLUSIONS: HbA1c predicts T2D in different common scenarios and is useful for identifying individuals with elevated T2D risk in both the short- and long-term.

LDL subfractions are associated with incident cardiovascular disease in the Malmö Prevention Project Study.

BACKGROUND AND AIMS: After assessing the risk for cardiovascular disease (CVD) based on traditional risk factors, decisions concerning lipid lowering therapy might remain uncertain. To investigate whether lipoprotein subfraction levels could aid these decisions, we assessed the association between lipoprotein subfractions and CVD, after adjustment for traditional risk factors including standard lipids. METHODS: Using a case-cohort design, participants were randomly drawn from the Malmö Prevention Project (MPP), a population-based prospective study of 18,240 participants, and supplemented with additional incident CVD events (5764 participants, 1784 CVD events). RESULTS: Low density lipoprotein particle number (LDL-P) and individual subfractions ranging in size from very-small to large were associated with CVD (continuous p value (pcont) < 0.001) while adjusting for age, sex, hypertension, smoking, and diabetes. After further adjustment for LDL-C, HDL-C, and triglycerides, very small LDL subfraction (b) (LDL-VS (b)) remained associated with CVD (HR = 1.23, 95% CI, 1.06 to 1.43 for top vs. bottom quartile, pcont = 0.03). Among participants with low/intermediate risk [without diabetes and with LDL-C <3.36 mmol/L (<130 mg/dL)], the fully adjusted HR for LDL-small (top vs. bottom quartile) was 1.48 (95% CI 1.02 to 2.17, pcont = 0.03). Among those with very-high risk (>20% 10-year risk of CVD), LDL-VS(a) and LDL-VS(b) were associated with CVD in fully adjusted models (HR = 1.37, 95% CI 1.12 to 1.67 and HR = 1.28, 95% CI 1.07 to 1.53, respectively, pcont≤0.03). CONCLUSIONS: Smaller LDL particles are associated with incident CVD independently of traditional risk factors, including standard lipids, in participants with low/intermediate and very-high risk, who might benefit from improved risk assessment.

A Multigene Test Could Cost-Effectively Help Extend Life Expectancy for Women at Risk of Hereditary Breast Cancer.

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.

Use of low density lipoprotein particle number levels as an aid in statin treatment decisions for intermediate risk patients: a cost-effectiveness analysis.

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.

Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history.

AIMS: Genetic risk scores (GRSs) have been associated with coronary heart disease (CHD) in large studies. We asked whether expanding an established 27-variant GRS (GRS27) to a 50-variant GRS (GRS50) improved CHD prediction and whether GRSs are independent of self-reported family history of CHD. METHODS AND RESULTS: The association between GRSs and incident CHD was assessed in Cox models adjusting for established risk factors in 23 595 participants of the Malmö Diet and Cancer study--a prospective, population-based study. During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. After adjustment for established risk factors, both GRS27 and GRS50 were associated with incident CHD [hazard ratio (HR) = 1.70 for high (top quintile) vs. low (bottom quintile) of GRS27; 95% confidence interval (CI): 1.48-1.94; Ptrend = 1.6 × 10(-15) and HR = 1.92 for GRS50; 95% CI: 1.67-2.20; Ptrend = 6.2 × 10(-22)]. Adding 23 single nucleotide polymorphisms (SNPs) to GRS27 improved risk prediction (P = 3 × 10(-6)). Further adjustment for self-reported family history did not appreciably change the risk estimates of either GRS27 (HR = 1.65; 95% CI: 1.45-1.89) or GRS50 (HR = 1.87; 95% CI: 1.63-2.14). The addition of GRS50 to established risk factors, including self-reported family history, improved discrimination (P < 0.0001) and reclassification (continuous net reclassification improvement index = 0.17, P < 0.0001). In young participants (below median age), those with high GRS50 had 2.4-fold greater risk (95% CI: 1.85-3.12) than those with low GRS50. CONCLUSION: The addition of 23 SNPs to an existing GRS27 improved CHD risk prediction and was independent of self-reported family history. Coronary heart disease risk assessment by GRS could be particularly useful in young individuals.

Genetic risk for atrial fibrillation could motivate patient adherence to warfarin therapy: a cost effectiveness analysis.

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.