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Importance: Nonadherence to statin guidelines is common. The solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotype is associated with simvastatin myopathy risk and is proposed for clinical implementation. The unintended harms of using pharmacogenetic information to guide pharmacotherapy remain a concern for some stakeholders., Objective: To determine the impact of delivering SLCO1B1 pharmacogenetic results to physicians on the effectiveness of atherosclerotic cardiovascular disease (ASCVD) prevention (measured by low-density lipoprotein cholesterol [LDL-C] levels) and concordance with prescribing guidelines for statin safety and effectiveness., Design, Setting, and Participants: This randomized clinical trial was performed from December 2015 to July 2019 at 8 primary care practices in the Veterans Affairs Boston Healthcare System. Participants included statin-naive patients with elevated ASCVD risk. Data analysis was performed from October 2019 to September 2020., Interventions: SLCO1B1 genotyping and results reporting to primary care physicians at baseline (intervention group) vs after 1 year (control group)., Main Outcomes and Measures: The primary outcome was the 1-year change in LDL-C level. The secondary outcomes were 1-year concordance with American College of Cardiology-American Heart Association and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for statin therapy and statin-associated muscle symptoms (SAMS)., Results: Among 408 patients (mean [SD] age, 64.1 [7.8] years; 25 women [6.1%]), 193 were randomized to the intervention group and 215 were randomized to the control group. Overall, 120 participants (29%) had a SLCO1B1 genotype indicating increased simvastatin myopathy risk. Physicians offered statin therapy to 65 participants (33.7%) in the intervention group and 69 participants (32.1%) in the control group. Compared with patients whose physicians did not know their SLCO1B1 results at baseline, patients whose physicians received the results had noninferior reductions in LDL-C at 12 months (mean [SE] change in LDL-C, -1.1 [1.2] mg/dL in the intervention group and -2.2 [1.3] mg/dL in the control group; difference, -1.1 mg/dL; 90% CI, -4.1 to 1.8 mg/dL; P < .001 for noninferiority margin of 10 mg/dL). The proportion of patients with American College of Cardiology-American Heart Association guideline-concordant statin prescriptions in the intervention group was noninferior to that in the control group (12 patients [6.2%] vs 14 patients [6.5%]; difference, -0.003; 90% CI, -0.038 to 0.032; P < .001 for noninferiority margin of 15%). All patients in both groups were concordant with CPIC guidelines for safe statin prescribing. Physicians documented 2 and 3 cases of SAMS in the intervention and control groups, respectively, none of which was associated with a CPIC guideline-discordant prescription. Among patients with a decreased or poor SLCO1B1 transporter function genotype, simvastatin was prescribed to 1 patient in the control group but none in the intervention group., Conclusions and Relevance: Clinical testing and reporting of SLCO1B1 results for statin myopathy risk did not result in poorer ASCVD prevention in a routine primary care setting and may have been associated with physicians avoiding simvastatin prescriptions for patients at genetic risk for SAMS. Such an absence of harm should reassure stakeholders contemplating the clinical use of available pharmacogenetic results., Trial Registration: ClinicalTrials.gov Identifier: NCT02871934.

Although public health campaigns stress leisure time physical activity (LTPA) as essential for obesity prevention, few epidemiological studies have focused on the association of specific types and intensities of LTPA and the clinical endpoints of overweight and obesity. Therefore, we prospectively assessed whether moderate- and vigorous-intensity as well as total LTPA were associated with the risk of becoming either overweight or obese using a prospective cohort design of 19,003 women enrolled in the Women's Health Study (WHS). Women reported their participation in walking and LTPA at baseline. During a median follow-up of 11.6 years, 7,865 women became overweight or obese. In multivariable-adjusted models that included demographic, lifestyle, and dietary factors, both vigorous-intensity and total LTPA showed a modest inverse relationship with the development of overweight/obesity. The hazard ratios (HR) and 95% confidence interval (CI) for the highest categories of vigorous-intensity LTPA (>2,000 kcal/week) and total LTPA (>3,000 kcal/week) compared with no LTPA were 0.79 (0.71-0.89) and 0.87 (0.78-0.96), respectively. In addition, a greater percentage of total LTPA spent performing vigorous intensity activities was associated with a lower risk of overweight/obesity (multivariable HR 0.93, 95% CI 0.87-0.98 for performing >50% compared with <50% of activity as vigorous). In conclusion, higher amounts of total LTPA should be encouraged to prevent obesity. Among those willing to participate in vigorous LTPA, and for whom such activities are not contraindicated, vigorous LPTA should be encouraged.

Low-density lipoprotein (LDL) cholesterol is the primary lipid parameter targeted to prevent myocardial infarction. Alternatively, non-high-density lipoprotein (HDL) cholesterol includes LDL cholesterol and other atherogenic particles but does not require a fasting sample. Non-HDL cholesterol and LDL cholesterol as predictors of first nonfatal myocardial infarction were compared in 303 patients and 297 controls matched for age, gender, and community within the Boston Area Health Study. Patients were white men or women aged <76 years living in the Boston area, without a history of myocardial infarction or angina pectoris, in whom symptoms of confirmed myocardial infarction began during the 24 hours before admission. After multivariate adjustment for coronary risk factors in unmatched analyses, the corresponding odds ratios (ORs) of a first nonfatal myocardial infarction for non-HDL cholesterol in the second, third, and fourth quartiles were 1.83 (95% confidence interval [CI] 1.07 to 3.14), 2.07 (95% CI 1.23 to 3.49), and 2.33 (95% CI 1.39 to 3.90) (p trend <0.01). For LDL cholesterol, the ORs were 1.10 (95% CI 0.67 to 1.81), 0.87 (95% CI 0.52 to 1.46), and 1.45 (95% CI 0.90 to 2.35) (p trend = 0.16). Including HDL cholesterol in the model increased the ORs and strengthened the test for a trend for LDL cholesterol, whereas the ORs were decreased and the test for a trend was weakened for non-HDL cholesterol. In conclusion, given that non-HDL cholesterol accounts for LDL cholesterol plus other atherogenic particles but does not require a fasting sample, this study suggests that non-HDL cholesterol may be at least as useful as LDL cholesterol to initially screen patients for risk of a first nonfatal myocardial infarction.

Background: Colorectal cancer and type 2 diabetes share many risk factors, and hyperinsulinemia appears to be associated with an increased risk of colorectal cancer. We used the concentration of plasma C-peptide (an indicator of insulin production) to determine whether insulin and insulin resistance are associated with the risk of developing colorectal cancer., Methods: We conducted a nested case-control study in the Physicians' Health Study. Plasma samples were collected from 14 916 cancer-free men from August 1982 through December 1984. Plasma C-peptide concentration, measured with an enzyme-linked immunosorbent assay, was available for 176 case patients who developed incident colorectal cancer through December 31, 1995, and 294 age- and smoking status-matched control subjects. Information on four other insulin resistance-related factors at baseline was obtained. We used conditional logistic regression models to investigate associations. All statistical tests were two-sided., Results: Plasma C-peptide concentration was positively associated with age, body mass index (BMI), and number of insulin resistance-related factors, and it was inversely associated with fasting time before the blood draw, alcohol consumption, and vigorous exercise. An increased concentration of plasma C-peptide was statistically significantly associated with an increased risk of colorectal cancer (relative risk [RR] for the highest versus lowest quintile of plasma C-peptide = 2.7, 95% confidence interval [CI] = 1.2 to 6.2; P(trend) =.047), after adjusting for age, smoking status, fasting, BMI, alcohol consumption, vigorous exercise, and aspirin assignment in the Physicians' Health Study. The association became even stronger when the analysis was further adjusted for factors related to insulin resistance other than insulin levels (RR for the highest versus lowest quintile = 3.4, 95% CI = 1.4 to 8.3; P(trend) =.02) or when data from case patients who were diagnosed during the first 5 years of follow-up were excluded (RR for the highest versus the lowest quintile = 3.4, 95% CI = 1.3 to 8.8; P(trend) =.03). Adjusting for plasma levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) did not materially change the results. There was no apparent modification of risk by BMI, insulin resistance-related factors, or vigorous exercise., Conclusion: Elevated insulin production, as reflected by elevated concentrations of plasma C-peptide, may predict the risk of developing colorectal cancer, independently of BMI, factors related to insulin resistance, or levels of IGF-I and IGFBP-3.