Background and objectives: High lipoprotein a [Lp(a)] and fibrinogen levels are suggested risk factors for coronary heart disease (CHD) and stroke morbidity and mortality. Experimental data strongly suggest that the mechanisms of atherothrombosis include an interaction between fibrinogen and Lp(a), but little clinical evidence of a synergism between these two parameters has been reported.
Design and methods: Within the frame of a prospective population study conducted in the area of Cremona (Lombardy, Italy), 343 women and 216 men aged > or =65 years were evaluated for clinical and biochemical cardiovascular risk factors. Lp(a) levels > or =30 mg/dL were observed in 22.7% and 23.9% of men and women, respectively. Fibrinogen levels were higher in women (p<0.0001). After a median follow-up of 6.3 years 107 deaths were recorded, of which 33 were due to CHD or ischemic stroke.
Results: The combined incidence rate of CHD and stroke mortality increased from 10.8 (per 1000 person-years) for subjects with either Lp(a) > or =30 mg/dL or fibrinogen within the 5th quintile of the gender-specific distribution to 38.4 for subjects with both Lp(a) > or =30 mg/dL and fibrinogen within the 5th quintile. Age (p<0.0001), insulin (p<0.0002) and the combination of high Lp(a) and fibrinogen (hazard ratio=3.11, p=0.014), but not fibrinogen or Lp(a) levels in isolation, were independent predictors of CHD and stroke mortality. In a subgroup of 447 subjects in whom C-reactive protein (CRP) was measured, CRP levels were not predictive of combined CHD and stroke mortality.
Interpretations and conclusions: Based on these results obtained in a relatively small population of elderly subjects, the association of high Lp(a) and fibrinogen levels appears to carry an increased risk of pooled CHD and stroke mortality.