C-reactive protein among community-dwelling hypertensives on single-agent antihypertensive treatment

Abstract

C-reactive protein (CRP) is a predictor of adverse cardiovascular outcomes. The effect of antihypertensive therapy on CRP levels is largely unknown. We undertook a cross-sectional study of CRP levels among participants with primary hypertension on single-agent antihypertensive therapy in the community-based biracial Genetic Epidemiology Network of Arteriopathy cohort. Linear regression models were used to assess the association of antihypertensive medication class with log-transformed CRP after adjustment for age, gender, ethnicity, body mass index, smoking, diabetes, hydroxymethylglutaryl CoA reductase inhibitor use, achieved blood pressure control (<140/90 mm Hg), serum creatinine and urine albumin-to-creatinine ratios. There were 662 participants in the cohort taking single-agent therapy for hypertension. Median CRP levels differed across participants: 0.40 mg/dL for those on diuretics, 0.34 mg/dL on calcium-channel blockers, 0.25 mg/dL on beta-blockers and 0.27 mg/dL on renin-angiotensin-aldosterone system (RAAS) inhibitors (P < .001). With multivariable adjustment, the group on RAAS inhibitors had a 20% lower mean CRP on average than the group on diuretics (P = .044), differences between other medication classes were not apparent. Heart rate had a strong association with CRP (P < .001). Antihypertensive medication class may influence inflammation, particularly in patients on RAAS inhibitors.

Introduction

Increasing evidence supports a relationship between C-reactive protein (CRP) levels and cardiovascular disease (CVD) and mortality,1, 2, 3 sudden cardiac death² and stroke.⁴ CRP is an acute phase protein that conveniently serves as an in vivo bioassay to gauge the overall degree of inflammation. Elevated CRP has also emerged as a non-traditional risk factor for adverse cardiovascular outcomes, though its contribution to predicting CVD outcomes is less impressive after traditional risk factors have been considered.5, 6 Hypertension is associated with elevated CRP,⁷ and among normotensive subjects, elevated CRP predicts future risk of hypertension.⁸ CRP is correlating more with systolic and pulse pressure, rather than with diastolic blood pressure (DBP), even in treatment naive patients. This relationship may reflect underlying atherosclerosis⁹ as elevated CRP also correlates with measures of arterial wave reflection and stiffness.¹⁰ Low CRP values, along with normal brain natriuretic peptide (BNP) levels, predict the absence of left ventricular hypertrophy (LVH) among hypertensive individuals.¹¹ Nevertheless, the effect of antihypertensive agents from different classes on low-grade inflammation measured by CRP has received relatively little attention so far.

The available data on the effect of antihypertensives from different classes on CRP is limited to mostly small trials. Some12, 13 but not all14, 15 studies report lower CRP values with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. To date, there is only one large, community-based study reporting on the relationship between antihypertensive medication class and CRP. Recently, Palmas et al reported an association of beta-blocker use with lower CRP values, based on the baseline cohort exam from the Multi-Ethnic Study of Atherosclerosis (MESA).¹⁶ This relationship was observed in both monotherapy (P < .001) and combination therapy groups (P = .021).

The Genetic Epidemiology Network of Arteriopathy (GENOA) is a National Heart Lung and Blood Institute (NHLBI) supported bi-racial cohort study of hypertensive sibships in the community. The primary goal of our study was to determine if there is an association between antihypertensive medication class and CRP among community-dwelling hypertensives on single-agent therapy.