Progressive Atherosclerosis and Incident Cardiovascular Disease Heme Oxygenase-1 Gene Promoter Microsatellite Polymorphism Is Associated With

[2.39, 12.42]; P <0.0001), enhanced atherosclerosis progression (median difference in atherosclerosis score [interquartile range], 2.1 [0.8, 5.6] versus 0.0 [0.0, 2.2] mm; P =0.0012), and a trend toward higher levels of oxidized phospholipids on apolipoprotein B-100 (median oxidized phospholipids/apolipoprotein B level [interquartile range], 11364 [4160, 18330] versus 4844 [3174, 12284] relative light units; P =0.0554). Increased cardiovascular disease risk in those homozygous for ≥ 32 repeats was also detected in a pooled analysis of 7848 participants of the Bruneck, SAPHIR, and KORA prospective studies (hazard ratio [95% confidence interval], 3.26 [1.50, 7.33]; P =0.0043). Conclusions — This study found a strong association between the HO-1 variable number tandem repeat polymorphism and cardiovascular disease risk confined to subjects with a high number of repeats on both HO-1 alleles and provides evidence for accelerated atherogenesis and decreased antioxidant defense in this vascular high-risk group. ( Arterioscler Thromb Vasc Biol . 2015;35:00-00.) Heme oxygenase-1 is a key antioxidant and cytoprotective enzyme, and a repeat length polymorphism in its gene promoter region impacts its expression. We found that this polymorphism is associated with cardiovascular risk such that subjects with high repeat lengths on both heme oxygenase-1 alleles suffer a substantially elevated risk. Moreover, we found evidence that oxidative stress and atherosclerosis at least partly mediate this risk elevation. The prospective population-based framework of the Bruneck Study with its high-quality data assessment allowed, for the first time, an investigation of this association both longitudinally and in the general population. This work may delimit a previously underappreciated cardiovascular high-risk group that merits particular preventive attention.