C-Reactive Protein Gene Variant and the Human Left Ventricular Growth Response to Exercise: Data From the LARGE Heart Study

Objective: increased levels of C-reactive protein (CRP) are associated with left ventricular (LV) hypertrophy. This association may be causal (either directly or indirectly) or simply a confounder resulting from the recognized relationship between CRP and vascular disease. We attempted to clarify this issue, by assessing the association of a variant of the CRP gene with exercise-induced left ventricular hypertrophy in young healthy males: homozygosity for the T (rather than C) allele of the CRP +1444C>T gene variant is associated with serum CRP levels which are 0.68 mg/L higher than carriers of the C allele. Methods and Results: LV mass was measured using cardiovascular magnetic resonance in 301 army recruits before and after all identical 12-week physical training program. Subjects were genotyped for the CRP +1444C>T gene variant. LV mass was 164.25 +/- 24.52 g at entry and increased with training (+3.77 +/- 10.77 g). This increase was greatest among those homozygous for the rare T allele (+8.17 +/- 12.09 vs. +3.37 +/- 10.58 for TT genotype vs. C-allele carriers respectively.. P = 0.033). Conclusions: CRP genotype is associated with a greater LV growth to exercise, supporting a causal association between CRP and LV growth. Whether such an association might be directly mediated or results from alterations in phenotypes which themselves drive LV growth (for instance, altered arterial compliance) is not clear.