Dataset Information

Statin Trials, Cardiovascular Events, and Coronary Artery Calcification: Implications for a Trial-Based Approach to Statin Therapy in MESA.

ABSTRACT: OBJECTIVES:This study sought to determine whether coronary artery calcium (CAC) could be used to optimize statin allocation among individuals for whom trial-based evidence supports efficacy of statin therapy. BACKGROUND:Recently, allocation of statins was proposed for primary prevention of atherosclerotic cardiovascular disease (ASCVD) based on proven efficacy from randomized controlled trials (RCTs) of statin therapy, a so-called trial-based approach. METHODS:The study used data from MESA (Multi-Ethnic Study of Atherosclerosis) with 5,600 men and women, 45 to 84 years of age, and free of clinical ASCVD, lipid-lowering therapy, or missing information for risk factors at baseline examination. RESULTS:During 10 years' follow-up, 354 ASCVD and 219 hard coronary heart disease (CHD) events occurred. Based on enrollment criteria for 7 RCTs of statin therapy in primary prevention, 73% of MESA participants (91% of those >55 years of age) were eligible for statin therapy according to a trial-based approach. Among those individuals, CAC = 0 was common (44%) and was associated with low rates of ASCVD and CHD (3.9 and 1.7, respectively, per 1,000 person-years). There was a graded increase in event rates with increasing CAC score, and in individuals with CAC >100 (27% of participants) the rates of ASCVD and CHD were 18.9 and 12.7, respectively. Consequently, the estimated number needed to treat (NNT) in 10 years to prevent 1 event varied greatly according to CAC score. For ASCVD events, the NNT was 87 for CAC = 0 and 19 for CAC >100. For CHD events, the NNT was 197 for CAC = 0 and 28 for CAC >100. CONCLUSIONS:Most MESA participants qualified for trial-based primary prevention with statins. Among the individuals for whom trial-based evidence supports efficacy of statin therapy, CAC = 0 and CAC >100 were common and associated with low and high cardiovascular risks, respectively. This information may guide shared decision making aimed at targeting evidence-based statins to those who are likely to benefit the most.

SUBMITTER: Mortensen MB

PROVIDER: S-EPMC5723240 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Statin Trials, Cardiovascular Events, and Coronary Artery Calcification: Implications for a Trial-Based Approach to Statin Therapy in MESA.

Mortensen Martin Bødtker MB Falk Erling E Li Dong D Nasir Khurram K Blaha Michael J MJ Sandfort Veit V Rodriguez Carlos Jose CJ Ouyang Pamela P Budoff Matthew M

JACC. Cardiovascular imaging 20170725 2 Pt 1

<h4>Objectives</h4>This study sought to determine whether coronary artery calcium (CAC) could be used to optimize statin allocation among individuals for whom trial-based evidence supports efficacy of statin therapy.<h4>Background</h4>Recently, allocation of statins was proposed for primary prevention of atherosclerotic cardiovascular disease (ASCVD) based on proven efficacy from randomized controlled trials (RCTs) of statin therapy, a so-called trial-based approach.<h4>Methods</h4>The study use ...[more]

PMID: 28624395

Similar Datasets

Project description:The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for cholesterol management defined new eligibility criteria for statin therapy. However, it is unclear whether this approach improves identification of adults at higher risk of cardiovascular events.To determine whether the ACC/AHA guidelines improve identification of individuals who develop incident cardiovascular disease (CVD) and/or have coronary artery calcification (CAC) compared with the National Cholesterol Education Program's 2004 Updated Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) guidelines.Longitudinal community-based cohort study, with participants for this investigation drawn from the offspring and third-generation cohorts of the Framingham Heart Study. Participants underwent multidetector computed tomography for CAC between 2002 and 2005 and were followed up for a median of 9.4 years for incident CVD.Statin eligibility was determined based on Framingham risk factors and low-density lipoprotein thresholds for ATP III, whereas the pooled cohort calculator was used for ACC/AHA.The primary outcome was incident CVD (myocardial infarction, death due to coronary heart disease [CHD], or ischemic stroke). Secondary outcomes were CHD and CAC (as measured by the Agatston score).Among 2435 statin-naive participants (mean age, 51.3 [SD, 8.6] years; 56% female), 39% (941/2435) were statin eligible by ACC/AHA compared with 14% (348/2435) by ATP III (P?<?.001). There were 74 incident CVD events (40 nonfatal myocardial infarctions, 31 nonfatal ischemic strokes, and 3 fatal CHD events). Participants who were statin eligible by ACC/AHA had increased hazard ratios for incident CVD compared with those eligible by ATP III: 6.8 (95% CI, 3.8-11.9) vs 3.1 (95% CI, 1.9-5.0), respectively (P<.001). Similar results were seen for CVD in participants with intermediate Framingham Risk Scores and for CHD. Participants who were newly statin eligible (n?=?593 [24%]) had an incident CVD rate of 5.7%, yielding a number needed to treat of 39 to 58. Participants with CAC were more likely to be statin eligible by ACC/AHA than by ATP III: CAC score >0 (n?=?1015): 63% vs 23%; CAC score >100 (n?=?376): 80% vs 32%; and CAC score >300 (n?=?186): 85% vs 34% (all P?<?.001). A CAC score of 0 identified a low-risk group among ACC/AHA statin-eligible participants (306/941 [33%]) with a CVD rate of 1.6%.In this community-based primary prevention cohort, the ACC/AHA guidelines for determining statin eligibility, compared with the ATP III, were associated with greater accuracy and efficiency in identifying increased risk of incident CVD and subclinical coronary artery disease, particularly in intermediate-risk participants.

Project description:BackgroundThe JUPITER trial showed that some patients with LDL-cholesterol concentrations less than 3·37 mmol/L (<130 mg/dL) and high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more benefit from treatment with rosuvastatin, although absolute rates of cardiovascular events were low. In a population eligible for JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values.Methods950 participants from the Multi-Ethnic Study of Atheroslcerosis (MESA) met all criteria for JUPITER entry. We compared coronary heart disease and cardiovascular disease event rates and multivariable-adjusted hazard ratios after stratifying by burden of CAC (scores of 0, 1-100, or >100). We calculated 5-year number needed to treat (NNT) by applying the benefit recorded in JUPITER to the event rates within each CAC strata.FindingsMedian follow-up was 5·8 years (IQR 5·7-5·9). 444 (47%) patients in the MESA JUPITER population had CAC scores of 0 and, in this group, rates of coronary heart disease events were 0·8 per 1000 person-years. 74% of all coronary events were in the 239 (25%) of participants with CAC scores of more than 100 (20·2 per 1000 person-years). For coronary heart disease, the predicted 5-year NNT was 549 for CAC score 0, 94 for scores 1-100, and 24 for scores greater than 100. For cardiovascular disease, the NNT was 124, 54, and 19. In the total study population, presence of CAC was associated with a hazard ratio of 4·29 (95% CI 1·99-9·25) for coronary heart disease, and of 2·57 (1·48-4·48) for cardiovascular disease. hsCRP was not associated with either disease after multivariable adjustment.InterpretationCAC seems to further stratify risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with measurable atherosclerosis could allow for more appropriate allocation of resources.FundingNational Institutes of Health-National Heart, Lung, and Blood Institute.

Project description:BackgroundAtherosclerosis and consequent risk of cardiovascular events or mortality can be accurately assessed by quantifying coronary artery calcium score (CACS) derived from computed tomography. HMG-CoA-reductase inhibitors (statins) are the primary pharmacotherapy used to reduce cardiovascular events, yet there is growing data that support statin use may increase coronary calcification. We set out to determine the likelihood of severe CACS in the context of chronic statin therapy.MethodsWe established a retrospective, case-control study of 1,181 U.S. veterans without coronary artery disease (CAD) from a single site, the Providence VA Medical Center. Duration of statin therapy for primary prevention was divided into 5-year categorical increments. The primary outcome was CACS derived from low-dose lung cancer screening computed tomography (LCSCT), stratified by CACs severity (none = 0; mild = 1-99; moderate = 100-399; and severe ≥400 AU). Statin duration of zero served as the referent control. Ordinal logistic regression analysis determined the association between duration of statin use and CACS categories. Proportional odds assumption was tested using likelihood ratio test. Atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index, and CKD (glomerular filtration rate of <60 ml/min/1.73 m2) were included in the adjustment models.ResultsThe mean age of the study population was 64.7±7.2 years, and 706 (60%) patients were prescribed a statin at baseline. Duration of statin therapy was associated with greater odds of having increased CACS (>0-5 years, OR: 1.71 [CI: 1.34-2.18], p<0.001; >5-10 years, OR: 2.80 [CI: 2.01-3.90], p<0.001; >10 years, OR: 5.30 [CI: 3.23-8.70], p<0.001), and the relationship between statin duration and CACS remained significant after multivariate adjustment (>0-5 years, OR: 1.49 [CI: 1.16-1.92], p = 0.002; >5-10 years, OR: 2.38 [CI: 1.7-3.35], p<0.001; >10 years, OR: 4.48 [CI: 2.7-7.43], p<0.001).ConclusionsLong-term use of statins is associated with increased likelihood of severe CACS in patients with significant smoking history. The use of CACS to interpret cardiovascular event risk may require adjustment in the context of chronic statin therapy.

Project description:BackgroundThere are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations.MethodsOur study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk).ResultsCompared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm2), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups.ConclusionsIndividuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.

Project description:ObjectiveTo analyze the role of serum sortilin in coronary artery calcification (CAC) and cardiovascular and cerebrovascular events (CCE) in maintenance hemodialysis (MHD) patients.MethodsOne hundred eleven patients with MHD ≥3 months were included in this study. The general data, clinical features, hematological data, and medication history of the patients were recorded. Eighty-five cases were examined by vascular color Doppler ultrasound, cardiac color Doppler ultrasound, lateral lumbar radiography, and coronary artery calcification score. The patients were followed up for a median time of 45 months. The primary endpoint was CCE or death from a vascular event, and the role of sortilin in this process was analyzed.ResultsAmong 85 MHD patients, 51 cases (60.00%) had different degrees of CAC. There were significant differences in diabetes, dialysis time, serum phosphorus, calcium-phosphorus product, medical history of phosphate binders, sortilin, and carotid artery plaque between 4 different degrees of calcification groups (p < 0.05). Logistic regression analysis showed that diabetes (OR = 5.475; 95% CI: 1.794-16.71, p = 0.003), calcium-phosphorus product (OR = 2.953; 95% CI: 1.198-7.279, p = 0.019), and sortilin (OR = 1.475 per 100 pg/mL; 95% CI: 1.170-1.858, p = 0.001) were independent risk factors for CAC. During the follow-up, 28 cases of 111 patients (25.23%) suffered from CCE. There were significant differences in CCE between mild, moderate, and severe CAC groups and noncalcification groups (p < 0.05). Cox regression analysis showed that diabetes mellitus (HR 3.424; 95% CI: 1.348-8.701, p = 0.010), CAC (HR 5.210; 95% CI: 1.093-24.83, p = 0.038), and serum sortilin (HR = 8.588; 95% CI: 1.919-38.43, p = 0.005) were independent risk factors for CCE. Besides, we proposed a cutoff value of 418 pg/mL for serum sortilin level, which was able to predict the occurrence of CCE with 75.0% sensitivity and 71.9% specificity. The area under the curve was 0.778 (95% CI: 0.673-0.883).ConclusionSortilin is newly found to be independently associated with CAC and CCE in MHD patients.

Dataset Information

Statin Trials, Cardiovascular Events, and Coronary Artery Calcification: Implications for a Trial-Based Approach to Statin Therapy in MESA.

Publications

Statin Trials, Cardiovascular Events, and Coronary Artery Calcification: Implications for a Trial-Based Approach to Statin Therapy in MESA.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets