Coronary Atherosclerosis Across the Continuum of Blood Pressure

In this issue of the American Journal of Hypertension, Yoon et al. examine the cross-sectional association between a classification of stage 1 hypertension, adapted from the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults, and coronary atherosclerosis among 4,666 adults who underwent coronary computed tomography angiography as part of a general health checkup.1,2 While this cross-sectional report did not provide an opportunity to examine the association between blood pressure (BP) and cardiovascular disease (CVD) outcomes, the subclinical coronary atherosclerosis findings do strengthen our understanding of the risk relationship between BP and CVD. The 2 primary observations in the Yoon et al. report were a 37% higher odds of coronary plaque for participants with stage 1 hypertension compared with those classified as having a normal BP and the presence of a linear relationship between progressively higher BP values and the presence of coronary artery plaque. The authors also reported that stage 1 hypertension was associated with a 36% higher odds for coronary stenosis <50%, but that there was no significant association for coronary stenosis ≥50%. Although this study primarily focused on the association of stage 1 hypertension with coronary atherosclerosis, perhaps the most important finding was the observation of a linear relationship between both systolic BP (SBP) and diastolic BP (DBP) with the presence of coronary plaque. The observed linear relationship among generally healthy middle-aged adults starting from an SBP of approximately 80 mm Hg and a DBP of just above 40 mm Hg is consistent with recent findings from the Multi-Ethnic Study of Atherosclerosis (MESA) in which there was a graded relationship for SBP values of 90–129 mm Hg with the presence of coronary artery calcium (CAC) and atherosclerotic cardiovascular disease (ASCVD) among healthy adults without traditional ASCVD risk factors.3 A J-shaped relationship between DBP and CVD has been reported from a number of studies.4–6 However, the linear relationship between DBP and coronary atherosclerosis observed in this study of relatively healthy adults adds support to the DBP J-curve phenomenon existing only as a result of confounding or reverse causation, and is in keeping with other reports, including a recent Mendelian randomization study that also showed a linear relationship between DBP and CVD.7 An important and novel feature of the current report is that all of the study participants had coronary computed tomography angiography performed as part of their general health checkup. This allowed for the investigation of whether different plaque subtypes or severity of stenosis occurred more or less frequently among patients with stage 1 hypertension compared with those with normal BP. A higher percentage of patients with stage 1 hypertension had calcified plaques compared with noncalcified or mixed plaques. However, there was a significant association between stage 1 hypertension with noncalcified and mixed plaques, but not calcified plaques. In addition, there was a significant association between stage 1 hypertension and the odds of stenosis <50%, but not with a stenosis ≥50%. While these differences between calcified and noncalcified plaques subtypes along with stenosis severity are thought-provoking, their pathophysiologic significance is less clear. Hypertension propagates atherosclerosis primarily via endothelial damage and arterial stiffening. The beginning stages of atherosclerosis are characterized by aggregation of macrophage foam cells and lipid deposition in the intima. Calcification of coronary plaques does not occur until later in the pathophysiological process. In this study, there was a higher prevalence of calcified plaques, defined as those plaques with a calcified area >50%, compared with noncalcified or mixed plaques among patients with stage 1 hypertension. Although the amount of calcified plaque as measured by the CAC score is strongly associated with a higher ASCVD risk, densely calcified plaques are thought to be more stable and less likely to rupture while mixed or spotty calcification plaques are thought to be associated with a higher risk of ASCVD events.8,9 Similarly, while significant stenosis may elicit angina it is not necessarily more likely to be the source of a plaque rupture event.10 Accordingly, recent advances in our understanding of plaque morphology, rupture, and CVD risk suggest that the number of plaques and/or the total atherosclerotic burden is the most important predictor of future ASCVD events rather than plaque morphology or severity of stenosis.10,11 Noninvasive measurement of an individual’s atherosclerotic burden via CAC scoring significantly improves ASCVD risk stratification beyond traditional ASCVD risk factors and is a guideline recommended test to refine ASCVD risk.12,13 In this study, the prevalence of coronary plaque and CAC was progressively higher for each successive increment in BP group. While there is a growing body of evidence to support coronary computed tomography angiography as the test of choice to detect and evaluate obstructive coronary artery disease among symptomatic patients it is not recommended for CVD risk stratification among asymptomatic persons, due a lack of improvement in risk prediction compared with CAC.11,14,15 CVD risk stratification was incorporated into the most recent ACC/AHA BP guideline as part of the decision-making process for starting antihypertensive medication in patients with stage 1 hypertension.1 While the guideline recommends calculation of a patient’s 10-year ASCVD risk based on traditional ASCVD risk factors, the measurement of CAC has been shown to improve the selection of patients most likely to benefit from antihypertensive medication.16 Overall, this study supports the importance of higher BP as a predictor of ASCVD risk across the continuum of SBP and DBP values and increases our awareness that a large proportion of middle-aged adults with stage 1 hypertension already have coronary atherosclerosis. These results not only highlight the linear association between BP and coronary atherosclerosis among a group of relatively healthy middle-aged adults, but also provide added support for the most recent ACC/AHA definition of hypertension as a BP of ≥130/≥80 mm Hg. Accordingly, while the decision to start antihypertensive medication for stage 1 hypertension should be determined as part of a clinician–patient discussion these results demonstrate that the noninvasive evaluation of coronary atherosclerosis provides a high yield test in this group of adults that may provide important information for clinicians and patients to consider in their decision-making process. The authors declared no conflict of interest.