Association between plasma alkaline phosphatase and C-reactive protein in the United States National Health and Nutrition Examination Survey 2005-2006: Evidence for the use of ALP in the recommendation of pharmacological intervention in cardiovascular disease

Matthew Webber, Bernard Cheung, Aisling Krishnan. University of Birmingham, Birmingham, United Kingdom.

Background: Almost half of all cardiovascular events occur in people below the threshold recommended for prescription of statins. C-reactive protein (CRP) is a powerful indicator of cardiovascular events and may add to risk prediction. Results from the JUPITER trial have indicated that patients with normal low-density lipoprotein levels but with high plasma CRP could benefit from statin therapy. Alkaline phosphatase (ALP) is an inflammatory marker like CRP. Its level is also raised in atherosclerosis and peripheral vascular disease. We therefore set out to analyze the relationship between ALP and CRP in the United States National Health and Nutrition Examination Survey 2005-2006 (NHANES).

Methods: The analysis included 4155 men and non-pregnant women over the age of 20. The relationship between log-transformed plasma ALP, CRP and cardiovascular disease was analyzed using univariate and multivariate analysis.

Results: The ALP level was significantly correlated with age, waist circumference, body mass index, blood pressure, exercise, alcohol, triglycerides, and other liver enzymes after adjusting for age, gender and ethnicity (p<0.001). ALP level was associated with a higher frequency of cardiovascular disease (p=0.02), hypertension (p=0.01) hypercholesterolemia (p=0.04), and diabetes (p=0.02). Compared to the lowest quartile of ALP, the adjusted odds ratio associated with the highest quartile were 1.9 (95%CI 1.1-3.5), 1.6 (95%CI 1.0-2.5), 1.5 (95%CI 1.1-2.1) and 1.7 (95%CI 1.0-2.4) for cardiovascular disease, hypertension, hypercholesterolemia and diabetes respectively. In multivariate analysis, log ALP was an independent predictor of log CRP (p=1.0×10-6). A multivariate model that included log ALP, ethnicity, glycohemoglobin, waist circumference, albumin, apolipoprotein B, gamma glutamyl transferase and uric acid explained 40% of the variance in log CRP.

Conclusions: ALP is associated significantly with CRP and related cardiovascular variables. This may make it a useful marker in determining overall cardiovascular risk and informing decisions on pharmacological intervention. Our findings warrant further investigation in the form of prospective research and randomized drug intervention trials to assess the utility of ALP against a panel of other markers in large cohorts and in diverse ethnic populations.