Plasma levels of complement C3 is associated with development of hypertension: a longitudinal cohort study

Abstract

Hypertension has been associated with raised plasma levels of complement factor 3 and 4 (C3 and C4). The nature of this association is unclear. This populationbased longitudinal study explored whether C3 or C4 is associated with development of hypertension. Blood pressure and plasma levels of C3 and C4 were determined in 2178 healthy men, aged 35-50 years, initially without treatment for hypertension. Incidence of hypertension and blood pressure increase over 15.7 (72.2) years follow-up was studied in relation to C3 and C4 at baseline. Among men with initially normal blood pressure (o160/95 mm Hg), incidence of hypertension (X160/95 mm Hg or treatment) was 32, 42, 37 and 47%, respectively, for men with C3 in the first, second, third and fourth quartile (trend: P ¼ 0.001). This relationship remained significant after adjustment for confounding factors. Among men without blood pressure treatment, systolic BP increase (mean þ standard error, adjusted for age, initial blood pressure and follow-up time) was 17.5 þ 0.8, 19.6 þ 0.9, 19.8 þ 0.8 and 20.8 þ 0.8 mm Hg, respectively, in the C3 quartiles (trend: P ¼ 0.004). C3 was not associated diastolic blood pressure at followup. Although C4 was associated with blood pressure at the baseline examination, there was no relationship between C4 and development of hypertension or future blood pressure increase. It is concluded that C3 in plasma is associated with future blood pressure increase and development of hypertension.

New insights into complement C3 and inflammation in hypertension

“…Associations implied from cross-sectional studies do not imply causation. However, the present study by Engstrom et al 27 points to a more causative role of inflammation in the development of hypertension. A reduction of blood pressure by antihypertensive agents also leads to a decrease in the levels of the inflammatory markers.…”

“…26 Does the complement system have a role in hypertension? In this issue of the Journal of Human Hypertension, Engstrom et al 27 studied more thanthem up for a mean of 15 years. They found that those subjects with a high baseline complement C3 levels were at a higher risk of developing hypertension in later life, which was independent of other risk factors.…”

“…This is consistent with their previous report that baseline C3 levels predict the future development of diabetes mellitus, 28 as well as other studies that have demonstrated high baseline CRP levels predicting the subsequent development of hypertension. 29 The study by Engstrom et al 27 further emphasises the role of inflammation in the development of hypertension. What is not clear from this study is the role of coexisting cardiovascular risk factors, such as diabetes and whether high baseline C3 and C4 levels also predict the development of atherosclerotic vascular disease, both asymptomatic (subclinical) and clinically manifest.…”

Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

“…A number of observational series in non-renal populations have reported positive associations between the circulating levels of components of the complement system, such as C3 and the terminal complement complex SC5b-9, and both prevalent [1,2,3,4,5] and incident [6,7,8,9,10] cardiovascular (CV) disease. Enhanced complement activation, particularly via the alternative complement activation pathway, occurs in haemodialysis (HD) patients largely as a consequence of blood-membrane interactions and is partially attenuated by the use of newer, biocompatible membranes [11,12,13,14].…”

Inflammation, obesity and risk of hypertension: shared pathways or independent risk factors?

“…In population-based studies, hypertension is usually associated with raised levels of various markers of inflammation. 1 Longitudinal studies over the last years have shown that markers of inflammation, such as white blood cells, 2 complement factor C3, 3 C-reactive protein (CRP), 4 fibrinogen 5 and a score of five acute-phase proteins, 6 are associated with incidence of hypertension or increasing blood pressure levels. These studies show that inflammation predicts the development of hypertension, and suggest that inflammation could have a function in this process.…”