Coronary Heart Disease Events in Framingham Participants with Differing Exposure to Risk Factors During Young Adulthood.

<p>Coronary Heart Disease Events in Framingham Participants with Differing Exposure to Risk Factors During Young Adulthood.</p

Characteristics of participants at the beginning of follow up, stratified by early life exposure to LDL.

<p>Characteristics of participants at the beginning of follow up, stratified by early life exposure to LDL.</p

Adjusted associations between SBP, DBP, LDL and HDL levels at different ages and CHD events.

<p>Hazard ratios (95% confidence intervals) are adjusted for age (via Cox model), sex, calendar year (via spline), body mass index, diabetes, years with diabetes, smoking status (current/past/never), pack-years of tobacco exposure (via spline), and use of blood pressure and lipid medications. The first column of results (for age 20–39) corresponds to the right-hand column of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154288#pone.0154288.t002" target="_blank">Table 2</a>. Categories for systolic blood pressure (SBP) are ≤120 (reference), 121–140, 141–160 and >160 mmHg; for diastolic blood pressure (DBP) are ≤80, 81–90, 91–100, and >100; for low-density lipoprotein cholesterol (LDL) are ≤100 (reference), 101–130, 131–160 and >160 mg/dl; and for high-density lipoprotein cholesterol (HDL) are >65 (reference), 51–65, 36–50, and ≤35 mg/dl. “P Overall” refers to a test of the overall contribution of the risk factor (including early, later, and current exposures) to the model. No participants had an average SBP>160 mmHg from age 20–39. The * indicates a truncated confidence interval.</p

Framingham Offspring Study Sample Examinations and Observation Period.

<p>Framingham Offspring Study Sample Examinations and Observation Period.</p

Young Adult Exposure to Cardiovascular Risk Factors and Risk of Events Later in Life: The Framingham Offspring Study

<div><p>Background</p><p>It is unclear whether coronary heart disease (CHD) risk factor exposure during early adulthood contributes to CHD risk later in life. Our objective was to analyze whether extent of early adult exposures to systolic and diastolic blood pressure (SBP, DBP) and low-and high-density lipoprotein cholesterol (LDL, HDL) are independent predictors of CHD events later in life.</p><p>Methods and Findings</p><p>We used all available measurements of SBP, DBP, LDL, and HDL collected over 40 years in the Framingham Offspring Study to estimate risk factor trajectories, starting at age 20 years, for all participants. Average early adult (age 20–39) exposure to each risk factor was then estimated, and used to predict CHD events (myocardial infarction or CHD death) after age 40, with adjustment for risk factor exposures later in life (age 40+). 4860 participants contributed an average of 6.3 risk factor measurements from in-person examinations and 24.5 years of follow-up after age 40, and 510 had a first CHD event. Early adult exposures to high SBP, DBP, LDL or low HDL were associated with 8- to 30-fold increases in later life CHD event rates, but were also strongly correlated with risk factor levels later in life. After adjustment for later life levels and other risk factors, early adult DBP and LDL remained strongly associated with later life risk. Compared with DBP≤70 mmHg, adjusted hazard ratios (HRs) were 2.1 (95% confidence interval: 0.8–5.7) for DBP = 71–80, 2.6 (0.9–7.2) for DBP = 81–90, and 3.6 (1.2–11) for DBP>90 (p-trend = 0.019). Compared with LDL≤100 mg/dl, adjusted HRs were 1.5 (0.9–2.6) for LDL = 101–130, 2.2 (1.2–4.0) for LDL = 131–160, and 2.4 (1.2–4.7) for LDL>160 (p-trend = 0.009). While current levels of SBP and HDL were also associated with CHD events, we did not detect an independent association with early adult exposure to either of these risk factors.</p><p>Conclusions</p><p>Using a mixed modeling approach to estimation of young adult exposures with trajectory analysis, we detected independent associations between estimated early adult exposures to non-optimal DBP and LDL and CHD events later in life.</p></div

The Cost-Effectiveness of Low-Cost Essential Antihypertensive Medicines for Hypertension Control in China: A Modelling Study

<div><p>Background</p><p>Hypertension is China’s leading cardiovascular disease risk factor. Improved hypertension control in China would result in result in enormous health gains in the world’s largest population. A computer simulation model projected the cost-effectiveness of hypertension treatment in Chinese adults, assuming a range of essential medicines list drug costs.</p><p>Methods and Findings</p><p>The Cardiovascular Disease Policy Model-China, a Markov-style computer simulation model, simulated hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring costs, disease-related costs, and quality-adjusted life years (QALYs) gained by preventing cardiovascular disease or lost because of drug side effects in untreated hypertensive adults aged 35–84 y over 2015–2025. Cost-effectiveness was assessed in cardiovascular disease patients (secondary prevention) and for two blood pressure ranges in primary prevention (stage one, 140–159/90–99 mm Hg; stage two, ≥160/≥100 mm Hg). Treatment of isolated systolic hypertension and combined systolic and diastolic hypertension were modeled as a reduction in systolic blood pressure; treatment of isolated diastolic hypertension was modeled as a reduction in diastolic blood pressure. One-way and probabilistic sensitivity analyses explored ranges of antihypertensive drug effectiveness and costs, monitoring frequency, medication adherence, side effect severity, background hypertension prevalence, antihypertensive medication treatment, case fatality, incidence and prevalence, and cardiovascular disease treatment costs. Median antihypertensive costs from Shanghai and Yunnan province were entered into the model in order to estimate the effects of very low and high drug prices. Incremental cost-effectiveness ratios less than the per capita gross domestic product of China (11,900 international dollars [Int$] in 2015) were considered cost-effective. Treating hypertensive adults with prior cardiovascular disease for secondary prevention was projected to be cost saving in the main simulation and 100$13,000 per QALY gained [95% uncertainty interval, Int$10,000 to Int$18,000]). Of all one-way sensitivity analyses, assuming adherence to taking medications as low as 25%, high Shanghai drug costs, or low medication efficacy led to the most unfavorable results (treating all hypertension, about Int$47,000, Int$37,000, and Int$27,000 per QALY were gained, respectively). The strengths of this study were the use of a recent Chinese national health survey, vital statistics, health care costs, and cohort study outcomes data as model inputs and reliance on clinical-trial-based estimates of coronary heart disease and stroke risk reduction due to antihypertensive medication treatment. The limitations of the study were the use of several sources of data, limited clinical trial evidence for medication effectiveness and harms in the youngest and oldest age groups, lack of information about geographic and ethnic subgroups, lack of specific information about indirect costs borne by patients, and uncertainty about the future epidemiology of cardiovascular diseases in China.</p><p>Conclusions</p><p>Expanded hypertension treatment has the potential to prevent about 800,000 cardiovascular disease events annually and be borderline cost-effective in China, provided low-cost essential antihypertensive medicines programs can be implemented.</p></div

CVD Policy Model-China structure.

<p>State transitions are numbered in the diagram. Transition 1 = remain in CVD-free state. Transition 2 = incident CVD. Transition 3 = non-CVD death. Transitions 4 and 5 = survival or case fatality. Transition 6 = survival with or without repeat CVD event in chronic CVD patients.</p

Effectiveness and cost-effectiveness of implementing different BP control guidelines in untreated Chinese adults aged 35–84 y with hypertension, averaged from the projections for 2015–2025, the CVD Policy Model-China.

<p>* All guideline strategies affect adults not previously treated for hypertension only, i.e., “aware/treated/uncontrolled” population not treated.</p><p>^† To convert cost input to Chinese currency, multiply by PPP rate (in this case, 3.52). To convert to $US using the current official exchange rate, multiply by (PPP/exchange rate), for example, 3.52/6.20, or by 5.68.</p><p>^§ Less than 2 x China’s GDP per capita.</p><p>Each successive strategy is compared with the prior strategy. Results are in 2015 international dollars and 2015 Chinese RMB. All results reported as cost-saving describe strategies projected to be less costly and more effective than the prior strategy. Ninety-five percent uncertainty intervals were calculated from the results of 1,000 probabilistic simulations.</p

One-way sensitivity analysis of hypertension treatment inputs.

<p>* WHO CHOICE lowest outpatient visit cost for China</p><p>^† Stage two twice yearly, stage one once yearly</p><p>^‡ Stage two four times yearly, stage one three times yearly</p><p>^Δ Less than 1 x China’s 2015 GDP per capita (</p><p>^§ Less than 2 x China’s 2015 GDP per capita and greater than 1 x GDP per capita (≥Int$11,906 and < Int$23,812)</p><p>**Less than 3 x China’s GDP per capita and greater than 2 x GDP per capita (≥Int$23,812 and </p><p>^¶ Greater than 3 x China’s GDP per capita (≥Int$35,718)</p><p>All estimates are ICERs, compared with the prior strategy. Results are in 2015 international dollars (2015 Chinese RMB). All results reported as cost saving describe strategies projected to be less costly and more effective than the prior strategy.</p