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Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention.

ABSTRACT: AIMS:Dementia is a major global challenge for health and social care in aging populations. A third of all dementia may be preventable due to cardiovascular risk factors. Intensive multi-domain intervention trials targeting primarily cardiovascular risk factors show improved cognitive function in people at risk. Such interventions will, however, be expensive to implement in all individuals at risk and will represent unrealistic economic tasks for most societies. Therefore, a risk score identifying high-risk individuals is warranted. METHODS AND RESULTS:In 61 664 individuals from two prospective cohorts of the Danish general population, we generated 10-year absolute risk scores for all-cause dementia from cardiovascular risk factors and genetics. In both sexes, 10-year absolute risk of all-cause dementia increased with increasing age, number of apolipoprotein E (APOE) ?4 alleles, number of genome-wide association studies (GWAS) risk alleles, and cardiovascular risk factors. The highest 10-year absolute risks of all-cause dementia seen in smoking women with diabetes, low education, APOE ?44 genotype, and 22-31 GWAS risk alleles were 6%, 23%, 48%, and 66% in those aged 50-59, 60-69, 70-79, and 80-100, respectively. Corresponding values for men were 5%, 19%, 42%, and 60%, respectively. CONCLUSION:Ten-year absolute risk of all-cause dementia increased with age, APOE ?4 alleles, GWAS risk alleles, diabetes, low education, and smoking in both women and men. Ten-year absolute risk charts for dementia will facilitate identification of high-risk individuals, those who likely will benefit the most from an early intervention against cardiovascular risk factors.

SUBMITTER: Juul Rasmussen I

PROVIDER: S-EPMC7672536 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention.

Juul Rasmussen Ida I Rasmussen Katrine Laura KL Nordestgaard Børge G BG Tybjærg-Hansen Anne A Frikke-Schmidt Ruth R

European heart journal 20201101 41

<h4>Aims</h4>Dementia is a major global challenge for health and social care in aging populations. A third of all dementia may be preventable due to cardiovascular risk factors. Intensive multi-domain intervention trials targeting primarily cardiovascular risk factors show improved cognitive function in people at risk. Such interventions will, however, be expensive to implement in all individuals at risk and will represent unrealistic economic tasks for most societies. Therefore, a risk score id ...[more]

PMID: 33022702

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Project description:This study was designed to develop a risk assessment chart for the clinical management and prevention of the risk of cardiovascular disease (CVD) in Iranian population, which is vital for developing national prevention programs. The Isfahan Cohort Study (ICS) is a population-based prospective study of 6504 Iranian adults ?35 years old, followed-up for ten years, from 2001 to 2010. Behavioral and cardiometabolic risk factors were examined every five years, while biennial follow-ups for the occurrence of the events was performed by phone calls or by verbal autopsy. Among these participants, 5432 (2784 women, 51.3%) were CVD free at baseline examination and had at least one follow-up. Cox proportional hazard regression was used to predict the risk of ischemic CVD events, including sudden cardiac death due to unstable angina, myocardial infarction, and stroke. The model fit statistics such as area under the receiver-operating characteristic (AUROC), calibration chi-square and the overall bias were used to assess the model performance. We also tested the Framingham model for comparison. Seven hundred and five CVD events occurred during 49452.8 person-years of follow-up. The event probabilities were calculated and presented color-coded on each gender-specific PARS chart. The AUROC and Harrell's C indices were 0.74 (95% CI, 0.72-0.76) and 0.73, respectively. In the calibration, the Nam-D'Agostino ?2 was 10.82 (p = 0.29). The overall bias of the proposed model was 95.60%. PARS model was also internally validated using cross-validation. The Android app and the Web-based risk assessment tool were also developed as to have an impact on public health. In comparison, the refitted and recalibrated Framingham models, estimated the CVD incidence with the overall bias of 149.60% and 128.23% for men, and 222.70% and 176.07% for women, respectively. In conclusion, the PARS risk assessment chart is a simple, accurate, and well-calibrated tool for predicting a 10-year risk of CVD occurrence in Iranian population and can be used in an attempt to develop national guidelines for the CVD management.

Project description:BackgroundCholesterol guidelines typically prioritize primary prevention statin therapy on the basis of 10-year risk of cardiovascular disease. The advent of generic pricing may justify expansion of statin eligibility. Moreover, 10-year risk may not be the optimal approach for statin prioritization. We estimated the cost-effectiveness of expanding preventive statin eligibility and evaluated novel approaches to prioritization from a Scottish health sector perspective.MethodsA computer simulation model predicted long-term health and cost outcomes in Scottish adults ≥40 years of age. Epidemiologic analysis was completed using the Scottish Heart Health Extended Cohort, Scottish Morbidity Records, and National Records of Scotland. A simulation cohort was constructed with data from the Scottish Health Survey 2011 and contemporary population estimates. Treatment and cost inputs were derived from published literature and health service cost data. The main outcome measure was the lifetime incremental cost-effectiveness ratio, evaluated as cost (2020 GBP) per quality-adjusted life-year (QALY) gained. Three approaches to statin prioritization were analyzed: 10-year risk scoring using the ASSIGN score, age-stratified risk thresholds to increase treatment rates in younger individuals, and absolute risk reduction (ARR)-guided therapy to increase treatment rates in individuals with elevated cholesterol levels. For each approach, 2 policies were considered: treating the same number of individuals as those with an ASSIGN score ≥20% (age-stratified risk threshold 20, ARR 20) and treating the same number of individuals as those with an ASSIGN score ≥10% (age-stratified risk threshold 10, ARR 10).ResultsCompared with an ASSIGN score ≥20%, reducing the risk threshold for statin initiation to 10% expanded eligibility from 804 000 (32% of adults ≥40 years of age without CVD) to 1 445 500 individuals (58%). This policy would be cost-effective (incremental cost-effectiveness ratio, £12 300/QALY [95% CI, £7690/QALY-£26 500/QALY]). Incremental to an ASSIGN score ≥20%, ARR 20 produced ≈8800 QALYs and was cost-effective (£7050/QALY [95% CI, £4560/QALY-£10 700/QALY]). Incremental to an ASSIGN score ≥10%, ARR 10 produced ≈7950 QALYs and was cost-effective (£11 700/QALY [95% CI, £9250/QALY-£16 900/QALY]). Both age-stratified risk threshold strategies were dominated (ie, more expensive and less effective than alternative treatment strategies).ConclusionsGeneric pricing has rendered preventive statin therapy cost-effective for many adults. ARR-guided therapy is more effective than 10-year risk scoring and is cost-effective.

Project description:The American College of Cardiology and the American Heart Association (ACC/AHA) cholesterol treatment guidelines have wide-scale implications for treating adults without history of atherosclerotic cardiovascular disease (ASCVD) with statins.To estimate the cost-effectiveness of various 10-year ASCVD risk thresholds that could be used in the ACC/AHA cholesterol treatment guidelines.Microsimulation model, including lifetime time horizon, US societal perspective, 3% discount rate for costs, and health outcomes. In the model, hypothetical individuals from a representative US population aged 40 to 75 years received statin treatment, experienced ASCVD events, and died from ASCVD-related or non-ASCVD-related causes based on ASCVD natural history and statin treatment parameters. Data sources for model parameters included National Health and Nutrition Examination Surveys, large clinical trials and meta-analyses for statin benefits and treatment, and other published sources.Estimated ASCVD events prevented and incremental costs per quality-adjusted life-year (QALY) gained.In the base-case scenario, the current ASCVD threshold of 7.5% or higher, which was estimated to be associated with 48% of adults treated with statins, had an incremental cost-effectiveness ratio (ICER) of $37,000/QALY compared with a 10% or higher threshold. More lenient ASCVD thresholds of 4.0% or higher (61% of adults treated) and 3.0% or higher (67% of adults treated) had ICERs of $81,000/QALY and $140,000/QALY, respectively. Shifting from a 7.5% or higher ASCVD risk threshold to a 3.0% or higher ASCVD risk threshold was estimated to be associated with an additional 161,560 cardiovascular disease events averted. Cost-effectiveness results were sensitive to changes in the disutility associated with taking a pill daily, statin price, and the risk of statin-induced diabetes. In probabilistic sensitivity analysis, there was a higher than 93% chance that the optimal ASCVD threshold was 5.0% or lower using a cost-effectiveness threshold of $100,000/QALY.In this microsimulation model of US adults aged 45 to 75 years [corrected], the current 10-year ASCVD risk threshold (?7.5% risk threshold) used in the ACC/AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (ICER, $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (?4.0% risk threshold) or $150,000/QALY (?3.0% risk threshold). The optimal ASCVD threshold was sensitive to patient preferences for taking a pill daily, changes to statin price, and the risk of statin-induced diabetes.

Project description:BACKGROUND:Worldwide implementation of risk-based cardiovascular disease (CVD) prevention requires risk prediction tools that are contemporarily recalibrated for the target country and can be used where laboratory measurements are unavailable. We present two cardiovascular risk scores, with and without laboratory-based measurements, and the corresponding risk charts for 182 countries to predict 10-year risk of fatal and non-fatal CVD in adults aged 40-74 years. METHODS:Based on our previous laboratory-based prediction model (Globorisk), we used data from eight prospective studies to estimate coefficients of the risk equations using proportional hazard regressions. The laboratory-based risk score included age, sex, smoking, blood pressure, diabetes, and total cholesterol; in the non-laboratory (office-based) risk score, we replaced diabetes and total cholesterol with BMI. We recalibrated risk scores for each sex and age group in each country using country-specific mean risk factor levels and CVD rates. We used recalibrated risk scores and data from national surveys (using data from adults aged 40-64 years) to estimate the proportion of the population at different levels of CVD risk for ten countries from different world regions as examples of the information the risk scores provide; we applied a risk threshold for high risk of at least 10% for high-income countries (HICs) and at least 20% for low-income and middle-income countries (LMICs) on the basis of national and international guidelines for CVD prevention. We estimated the proportion of men and women who were similarly categorised as high risk or low risk by the two risk scores. FINDINGS:Predicted risks for the same risk factor profile were generally lower in HICs than in LMICs, with the highest risks in countries in central and southeast Asia and eastern Europe, including China and Russia. In HICs, the proportion of people aged 40-64 years at high risk of CVD ranged from 1% for South Korean women to 42% for Czech men (using a ?10% risk threshold), and in low-income countries ranged from 2% in Uganda (men and women) to 13% in Iranian men (using a ?20% risk threshold). More than 80% of adults were similarly classified as low or high risk by the laboratory-based and office-based risk scores. However, the office-based model substantially underestimated the risk among patients with diabetes. INTERPRETATION:Our risk charts provide risk assessment tools that are recalibrated for each country and make the estimation of CVD risk possible without using laboratory-based measurements. FUNDING:National Institutes of Health.

Project description:IntroductionCardiovascular disease is a leading cause of mortality in the U.S. Although the risk of cardiovascular disease can be mitigated substantially by following a healthy lifestyle, adhering to a healthy diet and other healthy behaviors are limited by reduced food security. This study aims to determine the association between food security and cardiovascular disease risk.MethodsThree samples from the 2007-2014 National Health and Nutrition Examination Survey were examined: (1) 7,340 non-fasting adults (aged 40-79 years); (2) 13,518 non-fasting adults (aged 20-64 years); and (3) 6,494 fasting adults (aged 20-64 years). Food security was assessed using the U.S. Household Food Security Survey Module, with households categorized as having full, marginal, low, or very low food security. Regressions were conducted in 2018 to test the associations between food security status and odds of ≥20% 10-year cardiovascular disease risk among middle-aged to older adults (OR, 95% CI) and cardiovascular disease risk factors among all adults (β, 95% CI).ResultsCompared with adults with full food security, those with very low food security had higher odds of ≥20% 10-year cardiovascular disease risk (OR=2.36, 95% CI=1.25, 4.46), whereas those with marginal food security had higher systolic blood pressure (β=0.94 mmHg, 95% CI=0.09, 1.80). Compared with adults with full food security, adults with different levels of food security had higher BMIs (marginal: 0.76, 95% CI=0.26, 1.26; low: 0.97, 95% CI=0.34, 1.60; and very low: 1.03, 95% CI=0.44, 1.63) and higher odds of current smoking (marginal: OR=1.43, 95% CI=1.17, 1.75; low: OR=1.47, 95% CI=1.22, 1.77; and very low: OR=1.95, 95% CI=1.60, 2.37).ConclusionsAdults with food insecurity have elevated cardiovascular disease risk factors and excess predicted 10-year cardiovascular disease risk. Substantially improving food security may be an important public health intervention to reduce future cardiovascular disease in the U.S.Population

Project description:ObjectiveTo understand general practitioners' (GPs) use of individual risk factors (blood pressure and cholesterol levels) versus absolute risk in cardiovascular disease (CVD) risk management decision-making.DesignRandomised experiment. Absolute risk, systolic blood pressure (SBP), cholesterol ratio (total cholesterol/high-density lipoprotein (TC/HDL)) and age were systematically varied in hypothetical cases. High absolute risk was defined as 5-year risk of a cardiovascular event >15%, high blood pressure levels varied between SBP 147 and 179?mm?Hg and high cholesterol (TC/HDL ratio) between 6.5 and 7.2?mmol/L.Setting4 GP conferences in Australia.Participants144 Australian GPs.OutcomesGPs indicated whether they would prescribe cholesterol and/or blood pressure lowering medication. Analyses involved logistic regression.ResultsFor patients with high blood pressure: 93% (95% CI 86% to 96%) of high absolute risk patients and 83% (95% CI 76% to 88%) of lower absolute risk patients were prescribed blood pressure medication. Conversely, 30% (95% CI 25% to 36%) of lower blood pressure patients were prescribed blood pressure medication if absolute risk was high and 4% (95% CI 3% to 5%) if lower. 69% of high cholesterol/high absolute risk patients were prescribed cholesterol medication (95% CI 61% to 77%) versus 34% of high cholesterol/lower absolute risk patients (95% CI 28% to 41%). 36% of patients with lower cholesterol (95% CI 30% to 43%) were prescribed cholesterol medication if absolute risk was high versus 10% if lower (95% CI 8% to 13%).ConclusionsGPs' decision-making was more consistent with the management of individual risk factors than an absolute risk approach, especially when prescribing blood pressure medication. The results suggest medical treatment of lower risk patients (5-year risk of CVD event <15%) with mildly elevated blood pressure or cholesterol levels is likely to occur even when an absolute risk assessment is specifically provided. The results indicate a need for improving uptake of absolute risk guidelines and GP understanding of the rationale for using absolute risk.

Dataset Information

Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention.

Publications

Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention.

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