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Why is Atherosclerotic Cardiovascular Disease Risk Overestimated by the ACC/AHA Pooled Cohort Equation?

1 Feb, 15 | by Alistair Lindsay

The 2013 ACC/AHA Cholesterol Guidelines expand the recommendations for statin use to populations previously felt to be at lower risk. Central to risk-estimation in these guidelines is a new equation for determination of atherosclerotic cardiovascular disease (ASCVD) risk. However, this risk model has been criticized overestimating ASCVD risk in validation studies of the model.  Using the Women’s Health Study, Cook et al. sought to determine the reasons for risk-overestimation by the ACC/AHA model. Among 27,542 women, 632 experienced an ASCVD event, defined as any myocardial infarction, any stroke, or death from a cardiovascular cause. more…

Differences in Statin Eligible Patients across Guidelines

29 Jun, 14 | by Alistair Lindsay

Recent ACC/AHA guidelines recommend consideration of statin therapy among patients with a 7.5% 10-year risk of atherosclerotic cardiovascular disease (CVD).  In this study, the authors examined implications of these new guidelines as compared with previous European Society of Cardiology (ESC) and Adult Treatment Panel III (ATP III) guidelines in a Dutch population-based prospective cohort of 4,854 healthy participants over 55 years of age. In this cohort,  96.4% men and 65.8% women would be recommended statinsunder the new ACC/AHA guidelines. In contrast, 66.1% of men and 39.1% of women would be recommended statins under ESC guidelines and 52.0% of men and 35.5% of women would be recommended statins by ATP III guidelines.  Subgroup analyses demonstrated under ACC/AHA guidelines nearly all women age 65 or older would be recommended statin therapy. more…

Validation of the Pooled Cohort Risk Equations from Recent ACC/AHA Guidelines

29 Jun, 14 | by Alistair Lindsay

Recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the assessment of cardiovascular risk recommend a new 10-year atherosclerotic cardiovascular disease (CVD) risk prediction tool called the Pooled Cohort risk equation. This new predictive model developed from cohorts of patients that were largely studied prior to the year 2000.  In light of the declining CVD incidence since 2000, the external validity of the Pooled Cohort risk equation has been questioned.  The present study sought to validate the Pooled Cohort equation in a contemporary cohort of 10,997 individuals aged 45-79 years without a prior history of atherosclerotic CVD for whom the guidelines would recommend consideration of a statin.  In 47,481 person-years of follow-up, 192 coronary heart disease events and 146 strokes were observed. Differences in observed and predicted risk were small in patients for whom a statin should be considered, consistent with good model calibration.  Further, the C-index was 0.72 (95% CI 0.70 – 0.75) consistent with moderate discrimination. more…

Glycemic measurements are not helpful in CVD risk prediction among non-diabetics

8 Jun, 14 | by Alistair Lindsay

Several clinical guidelines recommend measurement of glycated hemoglobin (HbA1c) to guide cardiovascular risk (CVD) risk assessment. In this study, the authors examined the utility of adding HbA1c measurements to conventional risk factors in prediction of CVD among non-diabetic patients. Data from 73 prospective studies with nearly 300,000 non-diabetic patients without known CVD at enrollment was analyzed. Mean age was 58 years, 49% were women and mean HbA1c was 5.4%. Over a median follow-up duration of nearly 10 years, there were 20,840 fatal and nonfatal incident CVD events. Addition of HbA1c levels to risk prediction models with conventional CVD risk factors of age, sex, smoking, blood pressure, HDL and total cholesterol led to small changes in C-index (0.7434 to 0.7452; change of 0.0018, 95% CI 0.0003-0.0033) and net reclassification 0.42 (-0.63 to 1.48). Use of other glycemic measurements such as fasting glucose, random glucose and postload glucose were no better for CVD risk prediction than HbA1c. more…

Coronary artery calcium density is inversely associated with coronary risk

13 Apr, 14 | by Alistair Lindsay


Coronary calcium is associated with cardiovascular disease risk.  However, it may not only be the volume, but the density of coronary calcium that influences risk as more dense calcium may reflect stable plaque at lower risk of inciting coronary events.  The traditional Agatson method of scoring coronary calcium burden does not consider coronary calcium volume and density independently. In this prospective cohort study of 3,398 adults without known cardiovascular disease, the authors examined the predictive value of adding coronary calcium density to Agatston volume scores for cardiovascular disease risk. Over a median follow-up of more than 7 years, there were 265 cardiovascular events in the study population and the Agatston volume score of coronary calcium was positively associated with cardiovascular disease risk. However, the density score was inversely associated with cardiovascular disease risk. Furthermore, the addition of the density score improved a risk prediction model for cardiovascular disease. more…

Testosterone replacement associated with higher risk for adverse cardiovascular events

2 Feb, 14 | by Alistair Lindsay

Despite limited data on cardiovascular safety, rates of testosterone therapy are increasing dramatically. In a retrospective cohort study of 8,709 male Veterans with a low testosterone level, the authors sought to determine the association between use of testosterone therapy following coronary angiography and patient outcomes of all-cause mortality, myocardial infarction and stroke. more…

Influenza vaccine protects against adverse cardiovascular events

29 Dec, 13 | by Alistair Lindsay

Evidence supporting the use of influenza vaccine in patients at risk for coronary artery events largely comes from observational studies or small randomized trials (RCTs). In this study, the authors conducted a systematic review of 6 RCTs (5 published, 1 unpublished) comparing influenza vaccine to placebo on the rate of a composite of major adverse cardiovascular events (i.e. cardiovascular death or hospitalization for myocardial infarction, unstable angina, stroke, heart failure, or urgent coronary revascularization). The 5 published trials showed a pooled risk ratio (RR) of 0.64 (95% confidence interval [CI] 0.48 – 0.86; p<.003), translating to a number needed to treat of 58 to prevent 1 MACE. In these studies, the vaccine appeared more beneficial in patients with recent acute coronary syndromes (RR 0.45; 95% CI 0.32 – 0.63) compared to those with stable CAD (RR 0.94; 95% CI 0.55 – 1.61; p for interaction =.02). There was no association between receipt of influenza vaccine and cardiovascular mortality (pooled RR 0.81; 95% CI 0.3-1.83) or all-cause mortality (pooled RR 0.85; 95% CI 0.45-1.61). Addition of unpublished data did not change the results. more…

A Randomized Trial of the “Polypill” for Cardiovascular Risk Modification

22 Nov, 13 | by Alistair Lindsay

Long-term use of recommended cardiovascular (CV) risk modifying medications is low among patients at high-risk for CV events.  Fixed-dose drug combination (FDC) therapy may reduce treatment gaps by lowering non-adherence, cost, complexity and therapeutic inertia. However, FDC may also reduce tailoring of individual medications and thereby lead to suboptimal risk control. The UMPIRE (Use of Multidrug Pill in Reducing Cardiovascular Events) randomized, open-label trial compared FDC versus usual care among individuals with high risk (>15% risk over 5 years) for CV disease and clear indications for aspirin, statin, and blood pressure lowering medications. A total of 2004 participants were randomized to FDC or usual care. Primary outcomes included change in self-reported adherence to all medications and changes in LDL and systolic blood pressure (SBP) from baseline.  Overall, 88% of participants had established CAD. Median follow-up duration was 15 months. Patients treated with FDC has significantly improved adherence (RR 1.13, 95% CI 1.08 – 1.18) and change in SBP (-2.6 mm Hg, 95% CI -4.0 to -1.1 mmHg) and LDL (-4.2mg/dL, 95% CI -6.6 to -1.9 mg/dL). There were no significant differences in adverse events between the two groups. more…

Lipid-related markers improve cardiovascular disease prediction

2 Jul, 12 | by Alistair Lindsay

While the measurement and management of cholesterol forms an integral part of cardiovascular risk management, it has been suggested that risk assessment could be improved by the assessment of various additional lipid-related markers either to supplement or replace traditional cholesterol measurements.  The aim of this paper was to determine whether cardiovascular risk prediction could be improved by adding information on other lipid-related markers, including: apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2. more…

Coronary Artery Calcium Scanning Improves Risk Stratification

10 Sep, 11 | by Alistair Lindsay

In the JUPITER study, patients with low cholesterol levels but raised high-sensitivity C-reactive protein (hsCRP) levels were seen to benefit from treatment with rosuvastatin, although overall cardiovascular events were low.  In this study, the authors investigated whether the use of coronary artery calcium (CAC) scoring could further stratify risk in a population of patients from the Multi-Ethnic Study of Atherosclerosis (MESA) who all met criteria for entry into the JUPITER study. more…

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