Model Parameters.

<p>Model Parameters.</p

Sensitivity Analysis on Event Rate Parameters—2x MESA Event Rates.

<p>Note: A risk assessment and treatment strategy is said to dominate if it is less costly and more effective than both of the alternative strategies to which it is compared. Otherwise, the favored strategy may be incrementally more costly and more effective than ATP III, which was the standard of risk assessment when this study was conducted. If the incremental cost per unit of effect is less than or equal to $50,000, the alternative intervention is assumed to be favored, and an incremental cost-effectiveness ratio (ICER) is reported. If the ICER exceeds$50,000, but is positive, then ATP III is preferred. Mean costs and effects for each scenario, which are the basis for the decisions summarized in the table, are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116377#pone.0116377.s004" target="_blank">S3 Table</a>. Scenarios are identified by the scenario number on each row of the table.</p><p>Sensitivity Analysis on Event Rate Parameters—2x MESA Event Rates.</p

Averted CHD and CVD Events Per 1,000 Persons, Base-Case MESA Event Rates.

<p>Note: Simulated events per 1,000 persons, by risk assessment and treatment strategy. The results displayed in this table value outcomes in terms of averted events, but <i>not</i> QALYs. Results reflect all base-case model assumptions and 1x MESA event rates.</p><p>* Column displays results for the scenario where patients with CAC≥1 are advised to initiate statins (intensive therapy for CAC≥100, and standard therapy for 1≤CAC<100).</p><p>Averted CHD and CVD Events Per 1,000 Persons, Base-Case MESA Event Rates.</p

Study population characteristics presented as mean (standard deviation) or percent.

<p>Personal characteristics as reported at baseline. 86 participants had follow-up IMT measurements without valid baseline IMT measurements. Hypertension was defined by diastolic blood pressure ≥90, a systolic blood pressure ≥140 or self-reported history of hypertension with use of hypertensive medications.</p><p>CRP, C-reactive protein.</p

Cost-Effectiveness Acceptability Curves.

<p>Panel (a): 10-Year CVD Events, Treat CAC ≥ 1. Panel (b): 10-Year CVD Events, Treat CAC ≥ 100. Note: The cost-effectiveness acceptability curves show the proportion of simulations (vertical axis) that are cost-effective at a given willingness-to-pay threshold (horizontal axis). A mean CAC scanning cost of $100 and a mean statin cost of$180 is assumed in both plots (indirect costs and costs associated with incidentalomas are not included). The vertical intercept of each cost-effectiveness acceptability curve includes simulations that are cost saving and which result in a loss of fewer QALYs compared to the alternative scenarios. The intercept can be interpreted as the probability that a strategy would be accepted at a willingness-to-pay threshold of $0/QALY. For example, approximately 75$0/QALY threshold.</p

Schematic of the risk assessment and treatment strategies compared.

<p>* Patients with 1≤CAC<100 are advised to initiate standard statin therapy, which is assumed to provide a mean 35% reduction in the relative risk of CVD events. Patients with CAC≥100 are advised to begin intensive therapy, which provides a mean 45% reduction in the relative risk of CVD events.</p

Mean differences (95% CI) in IMT at baseline and in IMT progression over time associated with PM_2.5 concentrations prior to baseline and change between follow-up and baseline, with and without control for metropolitan area.

<p>Change was defined as the average concentration over the follow-up period: concentration at baseline such that a reduction in concentrations over time would have a negative change and increases in concentrations over time would be manifest as a positive change. Minimal adjustment included age, sex, and race/ethnicity. Moderately adjustment added control for education, a neighborhood socio-economic score (derived from census tract level data on education, occupation, median home values, and median household income), adiposity (1/height, 1/height², weight, waist, and 1/hip), and pack-years at baseline as well as a time-varying smoking status. Main models further adjusted for HDL, total cholesterol, statin use, diabetes mellitus (using the 2003 ADA fasting criteria algorithm), systolic blood pressure, diastolic blood pressure, hypertensive diagnosis, and hypertensive medications. In sensitivity analyses, we tested an extended model that also included physical activity, alcohol use, second-hand smoke exposures, C-reactive protein, creatinine, fibrinogen, occupation, and neighborhood noise among a smaller subset of the population with complete information.</p

Mean differences (95% CI) in IMT at baseline and in IMT progression over time associated with PM_2.5 concentrations prior to baseline and averaged over follow-up, with and without control for metropolitan area.

<p>Minimal adjustment included age, sex, and race/ethnicity. Moderately adjustment added control for education, a neighborhood socio-economic score (derived from census tract level data on education, occupation, median home values, and median household income), adiposity (1/height, 1/height², weight, waist, and 1/hip), and pack-years at baseline as well as a time-varying smoking status. Main models further adjusted for HDL, total cholesterol, statin use, diabetes mellitus (using the 2003 ADA fasting criteria algorithm), systolic blood pressure, diastolic blood pressure, hypertensive diagnosis, and hypertensive medications. In sensitivity analyses, we tested an extended model that also included physical activity, second-hand smoke exposures, alcohol use, C-reactive protein, creatinine, fibrinogen, occupation, and neighborhood noise among a smaller subset of the population with complete data.</p

Relation between risk factor clusters and differences in CIMT (Overall).

<p><b>Each cluster was compared to individuals without any risk factor (reference group).</b> CIMT, mean common carotid intima media thickness. BP, elevated blood pressure; OW, overweight; TC, elevated total cholesterol; smoking, current smoking.For most of the risk factors, the sum of the individual risk factor differences was smaller than the observed mean difference for the cluster in the overall analyses. For example, the mean difference in common CIMT for the blood pressure—smoking cluster was 0.077 mm, whereas the sum of the individual risk factors was 0.053 (i.e., 0.031 + 0.022). A similar finding was found for the smoking-blood pressure- overweight cluster. This observation suggests synergetic effects of risk factors on CIMT.</p

Relation between numbers of risk factors and differences in CIMT by race-ethnic group.

<p><b>Each number of risk factors was compared to individuals without any risk factor (reference group). CIMT, mean common carotid intima media thickness.</b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173393#pone.0173393.g003" target="_blank">Fig 3</a> presents the main findings of the overall analysis on risk factor clusters and CIMT. Within each risk factor cluster, there were graded relations with common CIMT. Within those with two risk factors, the cluster blood pressure-smoking had the highest CIMT (mean difference of 0.077 mm with those without risk factors) and the cluster with overweight- total cholesterol the least thickening (mean difference of 0.039 mm with those without risk factors), a difference reaching statistical significance with the cluster since the 95 confidence limits did not overlap. For people within the three risk factor cluster, elevated blood pressure, overweight and smoking had the highest common CIMT (0.084 mm). The pattern of the relationship between risk factor clusters and common CIMT were similar between sexes and race-ethnic groups, although some variation was observed between race-ethnic groups but was not significant due to limited minority samples sizes (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173393#pone.0173393.s001" target="_blank">S1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173393#pone.0173393.s002" target="_blank">S2</a> Figs). The interaction terms were not statistically significant.</p