The Contribution of Inflammation to the Development of Hypertension Mediated by Increased Arterial Stiffness

Abstract

Background: The mechanisms underlying the possible contribution of chronic inflammation to the development of hypertension remain unclear. We examined the longitudinal association of inflammation with the progression of vascular and/or renal abnormalities in the development of hypertension.

Methods and results: In 3274 middle-aged Japanese men without hypertension at the study baseline, brachial-ankle pulse wave velocity, blood pressure, estimated glomerular filtration rate, and serum CRP (C reactive protein) levels were measured annually during a 9-year period. During this study period, 474 participants (14.5%) developed hypertension. Analysis of the repeated-measures data revealed that sustained elevation of serum CRP levels was associated with a longitudinal increase of the brachial-ankle pulse wave velocity. A linear mixed model analysis revealed that higher log-transformed serum CRP values (log CRP) at each measurement were associated with a higher annual increase of the brachial-ankle pulse wave velocity (estimate=32.553±11.635 cm/s per log CRP, P=0.018), and that higher values of the brachial-ankle pulse wave velocity at each measurement were associated with a higher annual elevation of blood pressure (estimate=0.025±0.002 mm Hg per log CRP, P<0.001).

Conclusions: In middle-aged Japanese men without hypertension at study baseline, long-term active inflammation appears to be associated with a longitudinal increase of arterial stiffness. In turn, this longitudinal increase of arterial stiffness appears to be associated with longitudinal elevation of blood pressure to the hypertensive range. Thus, systemic inflammation may play a role in the pathogenesis of hypertension by the progression of arterial stiffness.

Keywords: C‐reactive protein; arterial stiffness; hypertension; inflammation.

Figure 1

Flow diagram of the participants enrolled in the study.

Figure 2

A, Annually measured values of the brachial‐ankle pulse wave velocity (baPWV), radial augmentation index (rAI), and estimated glomerular filtration rate during the observation period in participants with the log‐transformed serum C‐reactive protein levels in the lowest or intermediate tertile at the start of the study (open circles) and in those with levels in the highest tertile (closed circles). Because the measurements could not be conducted entirely continuously during the observation period, the annual changes of the data are plotted discontinuously for each of the participants. *=P<0.05 vs start; †=P<0.05 vs patients with log‐transformed serum C‐reactive protein levels in the lowest or intermediate tertile at the start of the study. B, Annually measured values of the systolic and diastolic blood pressure during the observation period in the participants with the log‐transformed serum C‐reactive protein levels in the lowest or intermediate tertile at the start of the study and those with the levels in the highest tertile. AN indicates annual observation; Annual observation ≥5 times, participants who underwent annual examinations more than 5 times; DBP, diastolic blood pressure; eGFRckep, estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration study equation; SBP, systolic blood pressure; Start, start of the study period.

Figure 3

A, Annually measured values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) during the observation period in participants with brachial‐ankle pulse wave velocity values in the lowest or intermediate tertile at the start of the study (open triangles) and in those with values in the highest tertile (closed triangles). †=P<0.05 vs patients with brachial‐ankle pulse wave velocity in the lowest/intermediate tertile at the start of the study. B, Annually measured values of SBP and DBP during the observation period in participants with radial augmentation index values in the lowest or intermediate tertile at the start of the study (open squares) and in those with values in the highest tertile (closed squares). AN indicates annual observation; Start, start of the study period. †=P<0.05 vs patients with radial augmentation index values in the lowest/intermediate tertile at the start of the study.

Figure 4

Mediation analyses to determine the association between log‐transformed serum C‐reactive protein levels and blood pressure. The mediation analyses describe the mediation of the relationship between the log‐transformed serum C‐reactive protein levels and blood pressure by the brachial‐ankle pulse wave velocity. baPWV indicates brachial‐ankle pulse wave velocity; DBP, diastolic blood pressure; log (CRP×10), log‐transformed serum C‐reactive protein level×10; SBP, systolic blood pressure.