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C-reactive protein elevation is associated with systolic hypertension in boys.

Question

  • In children and adolescents, is CRP elevation versus normal levels of systemic inflammation associated with elevated blood pressure?

Clinical Bottom Lines
1. Systolic blood pressure greater than or equal to 95th percentile is significantly associated with elevated C-reactive protein in boys. Subset analysis reveals perhaps a more significant association in the subset of African American boys only.
2. Obesity, low HDL, and Hispanic ethnicity are independently associated with elevated CRP.
3. CRP is an independent, additive risk factor for cardiovascular events in adults2,3,4, however its utility in the pediatric setting requires further investigation.


Summary of Key Evidence
1. Cross-section study
2. 6112 NHANES (National Health and Nutrition Examination Survey) participants, ages 8 to 17 years, surveyed in 1999-2004.
3. Exclusion criteria included CRP>10, and those receiving corticosteroids, stimulants, or estrogens.
4. BP was measured 3 times on 1 occasion via auscultation, with the first reading discarded, and the average of the last 2 readings taken.
5. CRP was measured with high sensitivity using latex enhanced nephelometry.
6. Patients were divided into groups with CRP>3 or less than or equal to 3.
7. Bivariate Analysis showed patients in the elevated CRP group had significant differences in older age, minority ethnicity, higher BMI, higher SBP, and low HDL.
8. Multivariate regression analysis was therefore adjusted for age, race/minority, BMI percentile, SBP, and low HDL level.
9. In the adjusted analysis, boys with SBP values greater than or equal to 95th percentile had significantly higher CRP (beta=0.38, p=0.018).
10. In the analysis repeated separately according to race/ethnicity, SBP >95th percentile and CRP was significantly associated only in African American boys (beta 0.46; P= 0.01). 11. Regardless of gender, BMI percentile, Hispanic ethnicity, and low HDL were independently associated with CRP levels.
12. SBP and CRP were not independently associated when SBP was defined as 90th percentile or less.

Additional Comments

  • • Inflammation and hypertension are thought to act together in the promotion of clinically symptomatic atherosclerotic plaque, resulting in angina, MI and stroke. 2, 3 • Adults with CRP>3 are considered at 1 to 2-fold increased risk of cardiovascular disease, relative to those with CRP<1.4
    • In prospective studies, hypertension and CRP in adults are considered independent risk factors for cardiovascular disease: Women’s Health Study participants with elevated CRP and BP, for example, demonstrate the lowest event-free survival rate.5, 6
    • Given the nature of this study, is not possible to determine causality between CRP and hypertension, nor are we able to determine long-term cardiovascular outcomes.
    • Study results would be more robust if CRP and BP were measured on at least 2 occasions.7
    • Ethnicity/race was self-defined in this study, and did not adjust for socioeconomic differences.
    • Subset analysis as described for African-American boys took into account so many potential variables simultaneously that it raises the possibility of statistical confounding – either finding a false association or losing some observations from the analysis altogether.10 • Measurement of inflammatory markers in obese youth would not currently lead to changes in treatment plan.
    • Further study of the pathogenesis of atherosclerosis in obese youth and the possible differences in atherosclerosis formation among ethnic groups is warranted.8,9
    • Further longitudinal study on children with elevated CRP and hypertension may elucidate the long term cardiovascular outcomes of at risk groups, and lead to focused treatment plans for those in high risk categories.

Citation

1. Land MB, Pearson TA, Vermilion RP, Auinger P, Fernandez ID. Elevated blood pressure, Race/Ethnicity, and C-reactive protein levels in Children and Adolescents. Pediatrics 2008; 122: 125-1257.
2. Tracey RP. Inflammation in cardiovascular disease. Circulation 1998; 9: 2000-2002.
3. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999; 340: 115-126.
4. Pearson TA, Mensah GA, Hong Y, Smith SC Jr. CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: overview. Circulation. 2004; 110(25):e543-3544.
5. Blake GJ, Rifai N, Buring J, Manson JE, Ridker PM. Blood pressure, C-reactive protein, and the risk of future cardiovascular events. Circulation. 2003; 108 (24): 2993-2999.
6. Campbell P, Blake GJ. C-reactive protein and hypertension. In: Ridker PM, Rifai N, eds. C-Reactive Protein and Cardiovascular Disease. St Laurent, Canada: MediEdition; 2006: 141-152.
7. Sorof JM, Poffenbarger T, Franco K, Portman R. Evaluation of white coat hypertension in children: importance of definitions of normal ambulatory blood pressure and the severity of casual hypertension. Am J Hypertension. 2001; 14(9): 855-860.
8. Kurian AK, Cardarelli KKM. Racial and ethnic differences in cardiovascular disease risk factors: a systemic review. Ethn Dis. 2007; 17(1): 143-152.
9. Mensah GA, Mokdad AH, Ford ES, Greenlund KJ, Croft JB. State of disparities in cardiovascular health in the United States. Circulation. 2005; 111(10): 1233-1241.
10. Koepsell, TD, Weiss NS. Epidemiologic Methods: Studying the Occurrence of Illness. Oxford University Press, USA; 2003.
CAT Author: Cathy Bonham, MD

CAT Appraisers: Beth Tarini, MD

Date appraised: February 4, 2009

Last updated June 15, 2009
Department of Pediatrics and Communicable Diseases
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