Lipoprotein-associated phospholipase A2 activity and risk of heart failure: The Rotterdam study.

AIMS: Evidence is accumulating that inflammation plays a role in the pathophysiology of heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has pro-inflammatory properties. We investigated whether Lp-PLA2 activity is associated with heart failure. METHODS AND RESULTS: Lp-PLA2 activity was determined in a random sample of 1820 subjects from the Rotterdam Study, a population-based cohort study among persons aged 55 years and over. During a mean follow-up of 6.7 years, 94 heart failure cases occurred. We excluded participants with heart failure or coronary heart disease at baseline and we accounted for incident coronary heart disease during follow-up. We used Cox proportional hazard models to compute hazard ratios adjusted for age, sex, non-HDL cholesterol, HDL cholesterol, body mass index, systolic blood pressure, diastolic blood pressure, hypertension, diabetes mellitus, smoking, and C-reactive protein. The hazard ratio per unit increase of Lp-PLA2 activity was 1.03 [95% confidence interval (95% CI 1.01-1.05]; P for trend was 0.011. Hazard ratios for the second, third, and fourth quartiles were 1.06 (95% CI 0.55-2.04), 1.43 (95% CI 0.73-2.81), and 2.33 (95% CI 1.21-4.49), respectively, using the lowest quartile of Lp-PLA2 activity as the reference category. CONCLUSION: This study suggests that Lp-PLA2 activity is independently associated with incident heart failure.

C-reactive protein and risk of heart failure. The Rotterdam Study.

BACKGROUND: Experimental studies have shown that the known biologic effects of proinflammatory cytokines could explain many aspects of the syndrome of heart failure. The inflammatory marker that presently seems most suitable to assess inflammation is C-reactive protein (CRP). This study was designed to investigate the association between serum CRP levels, as determined by high-sensitivity assay, and the occurrence of heart failure. METHODS: Serum CRP levels were available from 6437 men and women without heart failure, aged > or = 55 years, from the prospective population-based Rotterdam Study. Cox proportional hazards analysis was used to determine risk of heart failure for sex-specific quartiles of CRP. RESULTS: C-reactive protein levels in the highest versus the lowest quartile showed increased hazard ratios of incident heart failure. The age- and sex-adjusted hazard ratio was 2.64 (95% CI 2.04-3.43) for all participants. For men, the age adjusted hazard ratio was 4.37 (2.87-6.66), and for women, 1.86 (1.32-2.62). The interaction term of CRP with sex was highly significant. After additional adjustment for established cardiovascular risk factors, the association attenuated slightly in men and substantially in women, becoming 3.73 (2.40-5.78) and 1.42 (0.99-2.03), respectively. Excluding participants with prevalent coronary heart disease and accounting for incident coronary heart disease resulted in a further attenuation of the hazard ratios, which was proportionately larger in men than in women. CONCLUSIONS: C-reactive protein is strongly and independently associated with occurrence of heart failure in men. In women, the association is weaker and does not persist after accounting for established cardiovascular risk factors.

Arterial stiffness as the candidate underlying mechanism for postural blood pressure changes and orthostatic hypotension in older adults: the Rotterdam Study.

OBJECTIVE: To investigate whether arterial stiffening, one of the characteristics of the aging vascular system, is associated with orthostatic hypotension. DESIGN: Cross-sectional data of a cohort study in elderly men and women. PARTICIPANTS: We investigated the relationship between arterial stiffness and orthostatic hypotension within the framework of the Rotterdam Study, a population-based study in individuals aged 55 and older. The present study included 3362 subjects participating in the third examination phase. The carotid-femoral pulse wave velocity was used as measure of arterial stiffness. Orthostatic hypotension was assessed with blood pressure measurements in supine and standing position. RESULTS: Odds ratios for orthostatic hypotension increased through quartiles of pulse wave velocity; the age, gender and mean arterial pressure adjusted odds ratio in the last quartile of pulse wave velocity was 1.45 (95% confidence interval, 1.09-1.93) when compared with the first quartile (reference). In fully adjusted models estimates remained statistically significant. In subjects with higher stiffness we observed a higher drop in blood pressure but no significant change of heart rate. CONCLUSIONS: Arterial stiffness is independently associated with orthostatic hypotension. The drop in blood pressure levels and the contemporary attenuated response of heart rate to orthostatic challenge in subjects with stiffer arteries support the hypothesis that arterial stiffness may explain, at least in part, the reduced baroreflex observed in older adults.

Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study.

AIMS: To determine the prevalence, incidence rate, lifetime risk and prognosis of heart failure. METHODS AND RESULTS: The Rotterdam Study is a prospective population-based cohort study in 7983 participants aged > or =55. Heart failure was defined according to criteria of the European Society of Cardiology. Prevalence was higher in men and increased with age from 0.9% in subjects aged 55-64 to 17.4% in those aged > or =85. Incidence rate of heart failure was 14.4/1000 person-years (95% CI 13.4-15.5) and was higher in men (17.6/1000 man-years, 95% CI 15.8-19.5) than in women (12.5/1000 woman-years, 95% CI 11.3-13.8). Incidence rate increased with age from 1.4/1000 person-years in those aged 55-59 to 47.4/1000 person-years in those aged > or =90. Lifetime risk was 33% for men and 29% for women at the age of 55. Survival after incident heart failure was 86% at 30 days, 63% at 1 year, 51% at 2 years and 35% at 5 years of follow-up. CONCLUSION: Prevalence and incidence rates of heart failure are high. In individuals aged 55, almost 1 in 3 will develop heart failure during their remaining lifespan. Heart failure continues to be a fatal disease, with only 35% surviving 5 years after the first diagnosis.