Using Coronary Artery Calcium to Guide Antihypertensive ...



Proposal Title: Using Coronary Artery Calcium to Guide Antihypertensive Treatment Decisions in Asymptomatic Persons with Elevated Blood Pressure: Results from MESA

Abbreviated Title: CAC and NNT of Antihypertensives

Authors: John W McEvoy, Lara Kovell, Seth S Martin, Michael D Miedema, Kiang Liu, Joseph Yeboah, Matthew J Budoff, David C Goff, Wendy S Post, Khurram Nasir, Roger S Blumenthal, Michael J Blaha, others welcome

Type of Manuscript: Main Study, Longitudinal, Events

Data Analysis location and timing: Local

Genetic Information: None

PI approval: Yes

Keywords: Hypertension, Coronary Artery Calcium, NNT

Introduction/Rationale:

Hypertension remains a major cause of heart disease and stroke, with approximately 1 in 3 U.S. adults currently diagnosed as hypertensive and an additional 6-10% of Americans estimated to have undiagnosed hypertension.[pic]1 While effective anti-hypertensive therapies are widely available,[pic]2 there has been recent controversy regarding the optimal blood pressure (BP) cut-off to initiate therapy, particularly in persons over the age of 60 years. Specifically, a recent report by the eight panel appointed to the Joint National Committee (JNC) on Detection, Evaluation, and Treatment of High Blood Pressure recommended against initiating antihypertensive therapy until a systolic BP of 150 mmHg or higher in adults, without diabetes or chronic kidney disease, who are older than 60.[pic]3 This recommendation has been controversial4 and differs from that of other guidelines and advisories, the majority of which recommend a therapeutic systolic threshold of 140 mmHg or higher for persons younger than 80 years.[pic]5-7

Based on this new treatment threshold for persons over 60 years, it is estimated that over 13 million adults in the U.S. previously deemed eligible for therapy (by JNC-7) would no longer require treatment according to a report by panel members appointed to JNC-8.8 However, many of these individuals are at high cardiovascular disease risk (CVD) and estimates derived from observational and post-hoc randomized data suggest that the higher BP threshold in this group may lead to adverse clinical consequences due to under-treatment.[pic]9,10

In this context, there has also been a recent wave of interest in the incorporation of global CVD risk estimates into treatment decisions for hypertension. In a combined analysis from the Framingham and ARIC cohorts, Karmali et al. found that the majority of excess CVD events in these studies occurred in persons with BP levels in the range that would not typically warrant antihypertensive therapy based on JNC-8 (Karmali ACC abstract 2014). Further, the vast majority of these individuals had 10-year predicted atherosclerotic CVD (ASCVD) risk estimates of >5% (using the recent pooled cohort equation [PCE]11), suggesting that estimation of global CVD risk may facilitate more targeted allocation of antihypertensive therapies to those that would benefit the most, even with BP levels in the pre-hypertensive range. While this strategy remains to be tested, it is worth emphasizing that the use of global CVD risk is already applied to the treatment of high cholesterol, another major CVD risk-factor.12

Coronary Artery Calcium (CAC), measured by non-contrast cardiac CT, is a powerful subclinical marker of absolute and relative CVD risk and has been demonstrated to add incremental prognostic information to CVD risk estimates derived from traditional risk factors, such as the PCE.[pic]13-15 In addition, a number of analyses have suggested that CAC may facilitate allocation of other preventive therapies such as aspirin or a statin by identifying groups of individuals who are unlikely to receive substantial benefit, due to a high estimated number-needed-to-treat (NNT) in the absence of CAC, as well as those who are highly likely to receive a net benefit (typically demonstrating a low NNT in those with CAC>100).[pic]16-18

Therefore, we sought to determine whether CAC can also identify MESA subjects who are most likely to benefit from initiation and titration of anti-hypertensive therapies.

Hypotheses:

1. In persons less than 80 years of age who are not on antihypertensive therapy at the baseline MESA visit (2000-2002), and who have systolic BP (SBP) 120 mmHg but 80 mmHg but 140 mmHg but 90 mmHg but 100 mmHg and persons with both SBP ................
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