Personalized Prediction of Lifetime Benefits with Statin Therapy for Asymptomatic Individuals: A Modeling Study

Background: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. Methods and Findings: A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. Conclusions: We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy. Please see later in the article for the Editors' Summar

Personalized Prediction of Lifetime Benefits with Statin Therapy for Asymptomatic Individuals: A Modeling Study

Background: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. Methods and Findings: A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. Conclusions: We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy. Please see later in the article for the Editors' Summary

Remote second-hand tobacco exposure in flight attendants is associated with systemic but not pulmonary hypertension

Background: Second-hand tobacco smoke has been associated with cardiopulmonary dysfunction. We sought to examine the residual effects of remote second-hand smoke exposure on resting and exercise cardiopulmonary hemodynamics. We hypothesized that remote secondhand smoke exposure results in persistent cardiopulmonary hemodynamic abnormalities. Methods: Participants were non-smoking flight attendants who worked in airline cabins prior to the in-flight tobacco ban. Participants underwent clinical evaluations and completed smoke exposure questionnaires. We used Doppler echocardiography to measure pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) at rest and during supine bicycle ergometer exercise, using the validated formula TRV/VTIRVOT × 10 + 0.16, where VTIRVOT is the velocity time integral at the right ventricular outflow tract and TRV is the tricuspid regurgitation velocity. The group was divided into quartiles according to the degree of smoke exposure. Analysis of variance was used to determine the differences in hemodynamic outcomes. Results: Seventy-nine flight attendants were included in our analysis. Baseline characteristics among participants in each quartile of smoke exposure were similar except for history of systemic hypertension, which was more prevalent in the highest quartile. Peak exercise PASP rose to the same degree in all test groups (mean PASP 44 mm Hg, p = 0.25), and PVR increased by approximately 27% in all quartiles. There was no significant difference in pulmonary artery systolic pressure or pulmonary vascular resistance among quartiles of smoke exposure. Conclusions: We found that remote heavy second-hand smoke exposure from in-flight tobacco is associated with systemic hypertension but does not have demonstrable pulmonary hemodynamic consequences

Predictive Value of Updating Framingham Risk Scores with Novel Risk Markers in the U.S. General Population

Background: According to population-based cohort studies CT coronary calcium score (CTCS), carotid intima-media thickness (cIMT), high-sensitivity C- reactive protein (CRP), and ankle-brachial index (ABI) are promising novel risk markers for improving cardiovascular risk assessment. Their impact in the U.S. general population is however uncertain. Our aim was to estimate the predictive value of four novel cardiovascular risk markers for the U.S. general population. Methods and Findings: Risk profiles, CRP and ABI data of 3,736 asymptomatic subjects aged 40 or older from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 exam were used along with predicted CTCS and cIMT values. For each subject, we calculated 10-year cardiovascular risks with and without each risk marker. Event rates adjusted for competing risks were obtained by microsimulation. We assessed the impact of updated 10-year risk scores by reclassification and C-statistics. In the study population (mean age 56±11 years, 48% male), 70% (80%) were at low (<10%), 19% (14%) at intermediate (≥10–<20%), and 11% (6%) at high (≥20%) 10-year CVD (CHD) risk. Net reclassification improvement was highest after updating 10-year CVD risk with CTCS: 0.10 (95%CI 0.02–0.19). The C-statistic for 10-year CVD risk increased from 0.82 by 0.02 (95%CI 0.01–0.03) with CTCS. Reclassification occurred most often in those at intermediate risk: with CTCS, 36% (38%) moved to low and 22% (30%) to high CVD (CHD) risk. Improvements with other novel risk markers were limited. Conclusions: Only CTCS appeared to have significant incremental predictive value in the U.S. general population, especially in those at intermediate risk. In future research, cost-effectiveness analyses should be considered for evaluating novel cardiovascular risk assessment strategies

Predictive value of updating framingham risk scores with novel risk markers in the U.S. general population

Background: According to population-based cohort studies CT coronary calcium score (CTCS), carotid intima-media thickness (cIMT), high-sensitivity C- reactive protein (CRP), and ankle-brachial index (ABI) are promising novel risk markers for improving cardiovascular risk assessment. Their impact in the U.S. general population is however uncertain. Our aim was to estimate the predictive value of four novel cardiovascular risk markers for the U.S. general population. Methods and Findings: Risk profiles, CRP and ABI data of 3,736 asymptomatic subjects aged 40 or older from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 exam were used along with predicted CTCS and cIMT values. For each subject, we calculated 10-year cardiovascular risks with and without each risk marker. Event rates adjusted for competing risks were obtained by microsimulation. We assessed the impact of updated 10-year risk scores by reclassification and C-statistics. In the study population (mean age 56±11 years, 48% male), 70% (80%) were at low (<10%), 19% (14%) at intermediate (≥10-<20%), an

Approach to ergodicity in quantum wave functions

According to theorems of Shnirelman and followers, in the semiclassical limit the quantum wavefunctions of classically ergodic systems tend to the microcanonical density on the energy shell. We here develop a semiclassical theory that relates the rate of approach to the decay of certain classical fluctuations. For uniformly hyperbolic systems we find that the variance of the quantum matrix elements is proportional to the variance of the integral of the associated classical operator over trajectory segments of length $T_H$, and inversely proportional to $T_H^2$, where $T_H=h\bar\rho$ is the Heisenberg time, $\bar\rho$ being the mean density of states. Since for these systems the classical variance increases linearly with $T_H$, the variance of the matrix elements decays like $1/T_H$. For non-hyperbolic systems, like Hamiltonians with a mixed phase space and the stadium billiard, our results predict a slower decay due to sticking in marginally unstable regions. Numerical computations supporting these conclusions are presented for the bakers map and the hydrogen atom in a magnetic field.Comment: 11 pages postscript and 4 figures in two files, tar-compressed and uuencoded using uufiles, to appear in Phys Rev E. For related papers, see http://www.icbm.uni-oldenburg.de/icbm/kosy/ag.htm