Five-year Cardiovascular Disease Risk Research Articles

Effects of REM Sleep and systolic blood pressure variability on five-year cardiovascular disease risk

Effects of REM Sleep and systolic blood pressure variability on five-year cardiovascular disease risk

Updating cardiovascular disease risk prediction equations to account for lipid lowering treatment drop-in during follow up: a national data-linkage cohort

Abstract Background and Purpose No commonly recommended cardiovascular disease (CVD) risk prediction equations account for the effect of medications initiated during follow-up (treatment drop-in) in the cohort studies used to derive equations. We have previously demonstrated that treatment drop-in is common. In this study we aim to compare equations before and after accounting for lipid-lowering medication drop-in during follow-up. Methods De-identified individual-level linkage of multiple administrative health datasets in Aotearoa New Zealand was undertaken to establish a cohort of almost all New Zealanders without CVD or heart failure, alive and aged 30-74 years on December 31, 2006, with follow-up linkage to hospitalisations and mortality until 31 December 2018. We derived age- and sex-specific Cox regression models to predict 5-year CVD risk, using pre-defined routinely available CVD risk predictors, both with and without a time-dependent lipid-lowering medication drop-in variable. The drop-in effect was set at a 20% CVD risk reduction, based on randomised controlled trial evidence. We compared the observed and predicted risks of the two equations using calibration plots. Results During 19,728,300 person-years of follow-up (mean: 11.3 years), 1,746,695 people had 155,943 first CVD events. Kaplan-Meier adjusted 5-year CVD risk was 2.36% (95% CI: 2.33%, 2.39%) in women and 4.36% (95% CI: 4.31%, 4.40%) in men. 1,586,421 individuals were not taking lipid-lowering medications at baseline, among whom 371,415 initiated lipid-lowering medications during follow-up. Median predicted five-year CVD risk was slightly higher when using equations that accounted for lipid-lowering medication drop-in and identified significantly more individuals as ≥15% 5-year CVD risk than equations that did not (15,355 vs 9,680 in women and 46,603 vs 36,460 in men). As expected, the increased predicted risk in equations accounting for medication drop-in was most marked in the high-risk groups. Conclusions CVD risk prediction equations that do not adjust for treatment drop-in will underestimate risk and lead to undertreatment, particularly among the highest risk patients. Traditional methods to evaluate model performance are unable to identify the impact of treatment drop-in. We demonstrate that incorporating a time-dependent lipid-lowering medication effect from trials is likely to be an effective approach for addressing treatment drop-in in CVD risk prediction equations. Future studies will also need to address the impact of other common drop-in treatments, particularly blood pressure-lowering medications.

Validation and comparison of cardiovascular risk prediction equations in Chinese patients with Type 2 diabetes.

For patients with diabetes, the European guidelines updated the cardiovascular disease (CVD) risk prediction recommendations using diabetes-specific models with age-specific cut-offs, whereas American guidelines still advise models derived from the general population. We aimed to compare the performance of four cardiovascular risk models in diabetes populations. Patients with diabetes from the CHERRY study, an electronic health records-based cohort study in China, were identified. Five-year CVD risk was calculated using original and recalibrated diabetes-specific models [Action in Diabetes and Vascular disease: PreterAx and diamicroN-MR Controlled Evaluation (ADVANCE) and the Hong Kong cardiovascular risk model (HK)] and general population-based models [Pooled Cohort Equations (PCE) and Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR)]. During a median 5.8-year follow-up, 46 558 patients had 2605 CVD events. C-statistics were 0.711 [95% confidence interval: 0.693-0.729] for ADVANCE and 0.701 (0.683-0.719) for HK in men, and 0.742 (0.725-0.759) and 0.732 (0.718-0.747) in women. C-statistics were worse in two general population-based models. Recalibrated ADVANCE underestimated risk by 1.2% and 16.8% in men and women, whereas PCE underestimated risk by 41.9% and 24.2% in men and women. With the age-specific cut-offs, the overlap of the high-risk patients selected by every model pair ranged from only 22.6% to 51.2%. When utilizing the fixed cut-off at 5%, the recalibrated ADVANCE selected similar high-risk patients in men (7400) as compared to the age-specific cut-offs (7102), whereas age-specific cut-offs exhibited a reduction in the selection of high-risk patients in women (2646 under age-specific cut-offs vs. 3647 under fixed cut-off). Diabetes-specific CVD risk prediction models showed better discrimination for patients with diabetes. High-risk patients selected by different models varied significantly. Age-specific cut-offs selected fewer patients at high CVD risk especially in women.

Contemporary Cardiovascular Risk Assessment for Type 2 Diabetes Including Heart Failure as an Outcome: The Fremantle Diabetes Study Phase II.

Background: Type 2 diabetes (T2D) cardiovascular disease (CVD) risk assessment has limitations. The aim of this study was to develop a risk equation adding heart failure (HF) to conventional major adverse cardiovascular events (MACE, myocardial infarction, stroke, and CVD death) and allowing for non-CVD death. Methods: 1551 community-based people with T2D (mean age 66 years, 52% males) were followed from baseline in 2008–2011 for five years to the first CVD event/death. Cox and competing risk regression identified predictors of three-point MACE and four-point MACE (including HF). Discrimination was assessed by the area under the receiver-operating characteristic curve (AUC) and calibration by the Hosmer-Lemeshow test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for a 10% five-year CVD risk cut-off. Results: 143 participants (9.2%) experienced a three-point MACE during 7,111 person-years of follow-up and 245 (15.8%) a four-point MACE during 6,896 person-years. The best model was the competing risk four-point MACE (221 predicted events (14.3%), AUC 0.82 (95% CI: 0.79–0.85), Hosmer-Lemeshow test, p = 0.17, sensitivity 79.2%, specificity 68.1%, PPV 31.8%, NPV 94.6%) with validation in 177 adults with T2D from an independent population (AUC 0.81 (0.74–0.89). Conclusions: A validated four-point MACE competing risk model reliably predicts key T2D CVD outcomes.

A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk

Most individuals at high cardiovascular disease (CVD) risk worldwide do not receive any or optimal preventive drugs. We aimed to determine whether fixed dose combinations of generic drugs ('polypills') would promote use of such medications. We conducted a randomized, open-label trial involving 623 participants from Australian general practices. Participants had established CVD or an estimated five-year CVD risk of ≥15%, with indications for antiplatelet, statin and ≥2 blood pressure lowering drugs ('combination treatment'). Participants randomized to the 'polypill-based strategy' received a polypill containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Participants randomized to 'usual care' continued with separate medications and doses as prescribed by their doctor. Primary outcomes were self-reported combination treatment use, systolic blood pressure and total cholesterol. After a median of 18 months, the polypill-based strategy was associated with greater use of combination treatment (70% vs. 47%; relative risk 1.49, (95% confidence interval (CI) 1.30 to 1.72) p < 0.0001; number needed to treat = 4.4 (3.3 to 6.6)) without differences in systolic blood pressure (-1.5 mmHg (95% CI -4.0 to 1.0) p = 0.24) or total cholesterol (0.08 mmol/l (95% CI -0.06 to 0.22) p = 0.26). At study end, 17% and 67% of participants in polypill and usual care groups, respectively, were taking atorvastatin or rosuvastatin. Provision of a polypill improved self-reported use of indicated preventive treatments. The lack of differences in blood pressure and cholesterol may reflect limited study power, although for cholesterol, improved statin use in the polypill group counter-balanced use of more potent statins with usual care.

Changing Use of Implantable Cardioverter Defibrillators (ICDs) in New Zealand from 2002 to 2012

Background: New Zealand Cardiovascular disease (CVD) risk guidelines advocate targeted risk assessment with the intensity of management determined primarily on the estimated five-year CVD risk. However, clinicians often find it challenging to explain to patients what the conceptofCVDriskmeansanduse this to supportpatients to change ‘risky’ lifestyles and behaviour. “Your Heart Forecast” is a relatively simple dynamic graphical IT application that conveys multiple CVD risk communication messages individualised for each patient in a coherent story. It provides a graphical story at the time of consultation of current risk (where you are now), how you compare to a peer with ideal risk factor control, what happens to your risk as you get older if you make no changes (the Forecast), and what would happen to your risk in future if you were able to make changes (e.g. stop smoking). Our aim was to evaluate whether the Heart Forecast tool facilitated risk communication compared with a standard risk assessment session using the NZGG colour chart display. Methods and results: One hundred current smokers (age 30–65) without prior CVDwere enrolled in Southland primary care. Theywere randomised 1:1 to anurse-led risk assessment session with or without use of the Heart Forecast tool. Each patient had pre-assessment questionnaire, risk assessment session and same-day reassessment. The questionnaires evaluated patient understanding of the determinants of risk, their understanding of their own absolute short and longer-term CVD risk, and motivation to make lifestyle changes. Enrolment has been completed and resultswill be available for presentation.

Markedly different clustering of CVD risk factors in New Zealand Indian and European people but similar risk scores (PREDICT‐14)

To compare the cardiovascular disease (CVD) risk profiles of Indian and European patients from routine primary care assessments in the northern region of New Zealand. Anonymous CVD risk profiles were extracted from PREDICT (a web-based decision support program) for Indian and European patients aged 35-74 years. Linear regression models were used to obtain mean differences adjusted for age, gender and deprivation. At recruitment, Indian participants (n=8,830) were younger than Europeans (n=47,091), in keeping with national guidelines that recommend earlier CVD risk assessment for Indians. Compared with Europeans, a greater proportion of Indian participants lived in areas of higher deprivation and had a two to four-fold greater burden of diabetes in all age groups. Indian participants had a significantly lower proportion of smokers and a lower mean systolic blood pressure. The respective cardiovascular risk factor profiles lead to similar age-adjusted Framingham five-year CVD risk scores. National data sources indicate that there are higher rates of hospitalisations and deaths from CVD in Indians compared with Europeans. Our study found similar predicted CVD risk in these two populations despite markedly different clustering of risk factors, suggesting that the Framingham risk equation may underestimate risk in Indians. There is a need for better ethnicity coding to identify all South Asian ethnicities.

Aspirin for primary prevention: yes or no?

To assess benefit versus harm of aspirin for cardiovascular disease (CVD) primary prevention by age group, gender and risk category and to interpret these results in light of current New Zealand CVD risk assessment and management guidelines. Rates of benefit (avoided vascular events) and harm (additional major extracranial bleeds) for each gender and age group were calculated from data from the six randomised controlled trials included in the Anti-Thrombotic Trialists' (ATT) Collaboration meta-analysis. These rates were applied to CVD risk categories to calculate the net benefit or net harm likely to occur from the use of aspirin in primary prevention of CVD as monotherapy and when added to lipid and blood pressure-loweringtherapies. Benefits of aspirin monotherapy outweigh the harms for both men and women aged up to 80 years with calculated five-year CVD risk >15% in primary prevention. Harm may outweigh benefit for primary prevention for those over 80 years. For men 70-79 years the benefit of aspirin in primary prevention is marginal when added to lipid and blood pressure-lowering therapies. The recent ATT Collaboration meta-analysis has raised doubts about the relative safety of aspirin in primary prevention of CVD. However, modelling by risk category and age group suggests that current guidelines are justified in recommending aspirin for primary prevention of CVD in those with five-year CVD risk > or = 15% up to the age of 80 years. For men 70-79, consider lipid and blood pressure-lowering therapies first then reassess whether aspirin adds additional net benefit.

Should the first priority in cardiovascular risk management be those with prior cardiovascular disease?

Background: Cardiovascular disease (CVD) prevention guidelines typically dichotomise patients by history of CVD, as patients with prior CVD are assumed to be at high CVD risk, whatever their CVD risk...