Cardiovascular disease, fibrinogen and the acute phase response: associations with lipids and blood pressure in patients with chronic renal disease.

BACKGROUND

Fibrinogen, an acute phase reactant and coagulation factor is a major independent risk factor for cardiovascular disease (CVD) in the general population and may interact with lipids to promote CVD risk.

METHODS

Plasma fibrinogen, lipids and interleukin-6 were measured in 126 patients with chronic renal disease (low proteinuria (LP) and high proteinuria (HP) groups) or on maintenance dialysis (haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD)) and 31 healthy controls (N).

RESULTS

Fibrinogen was increased in all patients, and by each treatment category, when compared with the control group (421+/-143 all, 361+/-72 HD, 429+/-91 CAPD, 395+/-102 LP, 490+/-220 HP vs. 268+/-54 (N) mg/dl; P=0.0001) and correlated with urinary protein concentration, diastolic blood pressure and inversely with albumin. Interleukin-6, the mediator of the acute phase response, was increased in the combined patient group (3.2 vs. 1.5, median, pg/ml, P=.0002) and correlated with fibrinogen (r=0.32, P=0.01) and inversely with HDL-cholesterol (r=0.39, P < 0.01), consistent with a persistent inflammatory response. Patients with CVD complications (CVD +, n=46) were older, had an increased total:HDL-cholesterol ratio (7.7+/-4.3 CVD + vs. 5.9+/-1.8 CVD -, P < 0.005), but fibrinogen did not significantly differ (450+/-172 CVD + vs. 404+/-121 CVD -, P=0.09). Multiple logistic regression analysis identified categorisation of patients by values of fibrinogen and the total:HDL-cholesterol ratio greater than 95%, of the values for the controls as the only significant independent predictor of CVD complications. (Odds ratio for CVD complications of 13.5 (95%, CI 3.5-52) fibrinogen > 374 and total:HDL-cholesterol > 6.9 versus fibrinogen < 374 and total:HDL-cholesterol < 6.9).

CONCLUSIONS

The significant increase in fibrinogen in all renal disease states was associated with evidence of an acute phase response, protein losing states and hypertension. Persistence of an acute phase response was also correlated with an adverse lipid profile. Fibrinogen alone was a weak discriminator of prevalent CVD disease but in conjunction with an increased total:HDL-cholesterol ratio, was associated with the prevalence of CVD complications. Hypertension and a persistent acute phase response in patients with renal disease could contribute to CVD risk by effects upon fibrinogen and lipids, but requires confirmation by prospective evaluation.