Journal
HYPERTENSION
Volume 51, Issue 6, Pages 1651-1657Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.107.105668
Keywords
tonometry; inflammation; epidemiology; polymorphism; single nucleotide; genetics
Categories
Funding
- NCRR NIH HHS [M01 RR001066, M01 RR001066-26, M01-RR-01066] Funding Source: Medline
- NHLBI NIH HHS [R01 HL060040-04, N01HC25195, R01 HL071039-02, R01 HL076784-05, K24 HL004334-08, R01 HL077447, K24 HL004334, K23 HL080025, R01 HL077447-05, HL080025, R01 HL071039, U01 HL066582, HL70139, R01 HL076784, HL077447, R01 HL080124-05, R01 HL060040, N01 HC025195, R01 HL064753-04, HL04334, U01-HL66582, N01-HC-25195, K23 HL080025-05, R01 HL080124, HL076784, HL064753, U01 HL066582-04S1, HL60040, HL080124] Funding Source: Medline
- NIA NIH HHS [R01 AG028321, AG028321, R01 AG028321-04] Funding Source: Medline
- NIDDK NIH HHS [K24 DK080140-01] Funding Source: Medline
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Inflammation causes vascular dysfunction and perpetuates proatherosclerotic processes. We hypothesized that a broad panel of inflammatory biomarkers and single nucleotide polymorphisms in inflammatory genes is associated with vascular stiffness. We assessed 12 circulating inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor-II) in relation to tonometry variables (central pulse pressure, mean arterial pressure, forward pressure wave, reflected pressure wave, carotid-femoral pulse wave velocity, and augmentation index) measured in 2409 Framingham Heart Study participants (mean age: 60 years; 55% women; 13% ethnic/racial minorities). Single nucleotide polymorphisms (n=2195) in 240 inflammatory candidate genes were related to tonometry measures in 1036 white individuals. In multivariable analyses, biomarkers explained < 1% of any tonometry measure variance. Applying backward elimination, markers related to tonometry (P < 0.01) were as follows: tumor necrosis factor receptor-II ( inversely) with mean arterial pressure; C-reactive protein (positively) and lipoprotein-associated phospholipase-A2 (inversely) with reflected pressure wave; and interleukin-6 and osteoprotegerin (positively) with carotid-femoral pulse wave velocity. In genetic association analyses, lowest P values (false discovery rate < 0.50) were observed for rs10509561 (FAS), P=6.6x10(-5) for central pulse pressure and rs11559271 (ITGB2), P=1.1x10(-4) for mean arterial pressure. These data demonstrate that, in a community-based sample, circulating inflammatory markers tumor necrosis factor receptor-II (mean arterial pressure), C-reactive protein, lipoprotein-associated phospholipase-A2 activity (reflected pressure wave), interleukin-6, and osteoprotegerin (carotid-femoral pulse wave velocity) were significantly but modestly associated with measures of arterial stiffness and wave reflection. Additional studies are needed to determine whether variation in inflammatory marker genes is associated with tonometry measures.
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