Mark J. Pletcher

Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease

BACKGROUND The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health. METHODS We used the Coronary Heart Disease (CHD) Policy Model to quantify the benefits of potentially achievable, population-wide reductions in dietary salt of up to 3 g per day (1200 mg of sodium per day). We estimated the rates and costs of cardiovascular disease in subgroups defined by age, sex, and race; compared the effects of salt reduction with those of other interventions intended to reduce the risk of cardiovascular disease; and determined the cost-effectiveness of salt reduction as compared with the treatment of hypertension with medications. RESULTS Reducing dietary salt by 3 g per day is projected to reduce the annual number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000. All segments of the population would benefit, with blacks benefiting proportionately more, women benefiting particularly from stroke reduction, older adults from reductions in CHD events, and younger adults from lower mortality rates. The cardiovascular benefits of reduced salt intake are on par with the benefits of population-wide reductions in tobacco use, obesity, and cholesterol levels. A regulatory intervention designed to achieve a reduction in salt intake of 3 g per day would save 194,000 to 392,000 quality-adjusted life-years and

Trends in Opioid Prescribing by Race/Ethnicity for Patients Seeking Care in US Emergency Departments

10 billion to

Racial Differences in Incident Heart Failure among Young Adults

24 billion in health care costs annually. Such an intervention would be cost-saving even if only a modest reduction of 1 g per day were achieved gradually between 2010 and 2019 and would be more cost-effective than using medications to lower blood pressure in all persons with hypertension. CONCLUSIONS Modest reductions in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target.

Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study

CONTEXT National quality improvement initiatives implemented in the late 1990s were followed by substantial increases in opioid prescribing in the United States, but it is unknown whether opioid prescribing for treatment of pain in the emergency department has increased and whether differences in opioid prescribing by race/ethnicity have decreased. OBJECTIVES To determine whether opioid prescribing in emergency departments has increased, whether non-Hispanic white patients are more likely to receive an opioid than other racial/ethnic groups, and whether differential prescribing by race/ethnicity has diminished since 2000. DESIGN AND SETTING Pain-related visits to US emergency departments were identified using reason-for-visit and physician diagnosis codes from 13 years (1993-2005) of the National Hospital Ambulatory Medical Care Survey. MAIN OUTCOME MEASURE Prescription of an opioid analgesic. RESULTS Pain-related visits accounted for 156 729 of 374 891 (42%) emergency department visits. Opioid prescribing for pain-related visits increased from 23% (95% confidence interval [CI], 21%-24%) in 1993 to 37% (95% CI, 34%-39%) in 2005 (P < .001 for trend), and this trend was more pronounced in 2001-2005 (P = .02). Over all years, white patients with pain were more likely to receive an opioid (31%) than black (23%), Hispanic (24%), or Asian/other patients (28%) (P < .001 for trend), and differences did not diminish over time (P = .44), with opioid prescribing rates of 40% for white patients and 32% for all other patients in 2005. Differential prescribing by race/ethnicity was evident for all types of pain visits, was more pronounced with increasing pain severity, and was detectable for long-bone fracture and nephrolithiasis as well as among children. Statistical adjustment for pain severity and other factors did not substantially attenuate these differences, with white patients remaining significantly more likely to receive an opioid prescription than black patients (adjusted odds ratio, 0.66; 95% CI, 0.62-0.70), Hispanic patients (0.67; 95% CI, 0.63-0.72), and Asian/other patients (0.79; 95% CI, 0.67-0.93). CONCLUSION Opioid prescribing for patients making a pain-related visit to the emergency department increased after national quality improvement initiatives in the late 1990s, but differences in opioid prescribing by race/ethnicity have not diminished.

Comparing Impact and Cost-Effectiveness of Primary Prevention Strategies for Lipid-Lowering

BACKGROUND The antecedents and epidemiology of heart failure in young adults are poorly understood. METHODS We prospectively assessed the incidence of heart failure over a 20-year period among 5115 blacks and whites of both sexes who were 18 to 30 years of age at baseline. Using Cox models, we examined predictors of hospitalization or death from heart failure. RESULTS Over the course of 20 years, heart failure developed in 27 participants (mean [+/-SD] age at onset, 39+/-6 years), all but 1 of whom were black. The cumulative incidence of heart failure before the age of 50 years was 1.1% (95% confidence interval [CI], 0.6 to 1.7) in black women, 0.9% (95% CI, 0.5 to 1.4) in black men, 0.08% (95% CI, 0.0 to 0.5) in white women, and 0% (95% CI, 0 to 0.4) in white men (P=0.001 for the comparison of black participants and white participants). Among blacks, independent predictors at 18 to 30 years of age of heart failure occurring 15 years, on average, later included higher diastolic blood pressure (hazard ratio per 10.0 mm Hg, 2.1; 95% CI, 1.4 to 3.1), higher body-mass index (the weight in kilograms divided by the square of the height in meters) (hazard ratio per 5.7 units, 1.4; 95% CI, 1.0 to 1.9), lower high-density lipoprotein cholesterol (hazard ratio per 13.3 mg per deciliter [0.34 mmol per liter], 0.6; 95% CI, 0.4 to 1.0), and kidney disease (hazard ratio, 19.8; 95% CI, 4.5 to 87.2). Three quarters of those in whom heart failure subsequently developed had hypertension by the time they were 40 years of age. Depressed systolic function, as assessed on a study echocardiogram when the participants were 23 to 35 years of age, was independently associated with the development of heart failure 10 years, on average, later (hazard ratio for abnormal systolic function, 36.9; 95% CI, 6.9 to 198.3; hazard ratio for borderline systolic function, 3.5; 95% CI, 1.2 to 10.2). Myocardial infarction, drug use, and alcohol use were not associated with the risk of heart failure. CONCLUSIONS Incident heart failure before 50 years of age is substantially more common among blacks than among whites. Hypertension, obesity, and systolic dysfunction that are present before a person is 35 years of age are important antecedents that may be targets for the prevention of heart failure. (ClinicalTrials.gov number, NCT00005130.)

NIH Disease Funding Levels and Burden of Disease

Abstract Objective To assess whether active and passive smokers are more likely than non-smokers to develop clinically relevant glucose intolerance or diabetes. Design Coronary artery risk development in young adults (CARDIA) is a prospective cohort study begun in 1985-6 with 15 years of follow-up. Setting Participants recruited from Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California, USA. Participants Black and white men and women aged 18-30 years with no glucose intolerance at baseline, including 1386 current smokers, 621 previous smokers, 1452 never smokers with reported exposure to secondhand smoke (validated by serum cotinine concentrations 1-15 ng/ml), and 1113 never smokers with no exposure to secondhand smoke. Main outcome measure Time to development of glucose intolerance (glucose ≥ 100 mg/dl or taking antidiabetic drugs) during 15 years of follow-up. Results Median age at baseline was 25, 55% of participants were women, and 50% were African-American. During follow-up, 16.7% of participants developed glucose intolerance. A graded association existed between smoking exposure and the development of glucose intolerance. The 15 year incidence of glucose intolerance was highest among smokers (21.8%), followed by never smokers with passive smoke exposure (17.2%), and then previous smokers (14.4%); it was lowest for never smokers with no passive smoke exposure (11.5%). Current smokers (hazard ratio 1.65, 95% confidence interval 1.27 to 2.13) and never smokers with passive smoke exposure (1.35, 1.06 to 1.71) remained at higher risk than never smokers without passive smoke exposure after adjustment for multiple baseline sociodemographic, biological, and behavioural factors, but risk in previous smokers was similar to that in never smokers without passive smoke exposure. Conclusion These findings support a role of both active and passive smoking in the development of glucose intolerance in young adulthood.

Incidence and Clinical Implications of Isolation of Mycobacterium kansasii: Results of a 5-Year, Population-Based Study

Context Which lipid-lowering policies with statins are cost-effective? Contribution This modeling exercise found that the Adult Treatment Panel III guidelines, which recommend treatment based on cholesterol level and estimated coronary heart disease risk, are reasonably cost-effective if statins cost about

Cost-Effectiveness of Statin Therapy for Primary Prevention in a Low-Cost Statin Era

1.50 to

Association Between Marijuana Exposure and Pulmonary Function Over 20 Years

2.20 per pill. At costs lower than

Prehypertension during Young Adulthood and Coronary Calcium Later in Life

0.10 per pill, treating all persons with LDL cholesterol levels greater than 3.4 mmol/L (>130 mg/dL) could be a better strategy. Implication Optimum policies for lipid lowering with statins are highly dependent on statin costs. The Editors Coronary heart disease (CHD) is the leading cause of death in the United States (1). Inhibitors of HMG-CoA reductase, known as statins, lower cholesterol and prevent CHD events and mortality (2, 3). However, statins are expensive and sometimes cause side effects, which makes it difficult for patients, physicians, and policymakers to decide who should receive them. The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III), published by the National Cholesterol Education Program in 2001 (4) and updated in 2004 (3), provides comprehensive recommendations on when and how to treat high cholesterol levels with statins. These guidelines recommend treatment on the basis of a combination of cholesterol level and estimated CHD risk, with more aggressive cholesterol treatment thresholds recommended for patients with higher estimated risk. Adherence to ATP III guidelines is modest (5, 6), and many questions remain about strategys cost, complexity, and efficiency (6). Previous cost-effectiveness analyses (719) show that statin therapy is generally cost-effective for secondary prevention and for high-risk primary prevention but do not focus on population-level impact or average cost-effectiveness across the heterogeneous U.S. population, including such subgroups of patients as those with low risk but very high cholesterol levels. Also, it is unclear whether the ATP III approach to risk stratification, in which risk is formally assessed only for patients with 2 or more established risk factors, is the simplest and most cost-effective way of targeting statin therapy. Finally, ATP III bases treatment decisions on both risk and cholesterol level. The 2004 update to ATP III (3) notes that treatment of high-risk subgroups may be useful even when cholesterol levels are low, which suggests that a more purely risk-based approach may be simpler and more cost-effective than the ATP III approach. An even simpler algorithm based on patient age might provide similar cost-effectiveness, given that age is the primary driver of CHD risk (20). The CHD Policy Model is a mathematical state-transition model of CHD in the United States that can be used to project event rates and costs related to CHD. We used the model to evaluate ATP III primary prevention guidelines and to compare the strategys overall impact, cost, and cost-effectiveness with alternative risk- and age-based strategies under varying assumptions about the cost and side effects of statins. Methods Structure of the Model The CHD Policy Model is a computer-simulated, state-transition (Markov cohort) model of CHD incidence, prevalence, mortality, and costs among persons older than 35 years in the U.S. population. The demographicepidemiologic submodel predicts CHD incidence and non-CHD mortality among persons without CHD, stratified by age, sex, diastolic blood pressure, smoking status, high-density lipoprotein (HDL) cholesterol level, low-density lipoprotein (LDL) cholesterol level, diabetes mellitus, and use of statin therapy. After CHD develops, a bridge submodel characterizes the initial CHD event (cardiac arrest, myocardial infarction, or angina) and its sequelae over 30 days. A disease history submodel then predicts subsequent CHD events, revascularization procedures, CHD mortality, and non-CHD mortality among patients with CHD, stratified by age, sex, and history of events. Each health state and event has an annual cost and quality-of-life adjustment. All population distributions, risk factor levels, coefficients, event rates, case-fatality rates, costs, and quality-of-life adjustments can be modified for forecasting simulations. More details about the model have been published elsewhere (2123) and are also in the Appendix. Data Sources We used population size projections for 2000 to 2050, provided by the 2000 U.S. Census (24), and data from the National Health and Nutrition Examination Survey, 1999 to 2004 (25), to estimate joint distributions of risk factor values in the U.S. population. We estimated the background prevalence of CHD in 2000 from the National Health Interview Survey, 2000 (26). We estimated CHD deaths, prehospital deaths from cardiac arrest, and non-CHD deaths from U.S. Vital Statistics (27) on the basis of codes from the International Classification of Diseases, 10th revision. We obtained case-fatality and revascularization rates and the number of patients who had myocardial infarctions or out-of-hospital cardiac arrests and survived to hospital discharge from the National Hospital Discharge Survey (NHDS) (28) and complementary sources (Appendix). We estimated -coefficients that were conditional on age and sex by using examinations 9 to 13 of the original Framingham cohort and examinations 1 to 6 of the offspring (29) (Appendix). The LDL cholesterol coefficient decreases in magnitude with increasing age in the model (LDL cholesterol is a weaker risk factor in older adults), as estimated in the Framingham data (Appendix). Statin efficacy was modeled via LDL cholesterollowering. Our model closely replicated the reduction in coronary events with statins (30) and approximated the cost-effectiveness ratios of individual trials (31, 32) when we used their outcomes data (Appendix). We estimated total health care costs from the perspective of the health care system by using national data from the Centers for Medicare & Medicaid Services (33). We estimated the CHD cost component by using California data (34), deflated by using cost-to-charge ratios (35) and the ratio of the U.S. national average costs to the California average (36) and then inflated to 2006 dollars by using the Bureau of Labor Statistics Consumer Price Index for Medical Care Costs (37). We based health-related quality-of-life weights on observational data (38) and discounted costs and quality-adjusted life-years (QALYs) at a rate of 3% per year. Statin Therapy Assumptions We categorized statin drugs and doses that decrease LDL cholesterol level by approximately 27% (such as fluvastatin, 40 mg; lovastatin, 20 mg; pravastatin, 20 mg; and simvastatin, 10 mg) as low intensity and those that decrease it by approximately 55% (such as atorvastatin, 80 mg, and rosuvastatin, 40 mg) as high intensity (39, 40). We estimated direct medication costs for the base-case scenario by averaging the lowest average wholesale price reported in the 2006 National Drug Data File for low-intensity statins (