Description:
<jats:sec xml:lang="en"><jats:title>Background</jats:title><jats:p xml:lang="en">Haptoglobin (Hp) is an abundant plasma protein with antioxidant properties. The Hp 2‐2 genotype has previously been linked to coronary heart disease risk in individuals with elevated glycosylated hemoglobin (HbA<jats:sub>1c</jats:sub>). We investigated the association of Hp and HbA<jats:sub>1c</jats:sub>with cardiovascular disease (<jats:styled-content style="fixed-case">CVD</jats:styled-content>) in the longitudinal, population‐based Bruneck Study.</jats:p></jats:sec><jats:sec xml:lang="en"><jats:title>Methods and Results</jats:title><jats:p xml:lang="en">Hp genotype was determined by polymerase chain reaction according to standard procedures and HbA<jats:sub>1c</jats:sub>concentration by a Diabetes Control and Complications Trial‐aligned assay. HbA<jats:sub>1c</jats:sub>was measured in 1995, 2000, and 2005. Occurrence of the combined<jats:styled-content style="fixed-case">CVD</jats:styled-content>endpoint of myocardial infarction or stroke was recorded between 1995 and 2010. Outcome analyses employed the Cox proportional hazards model with HbA<jats:sub>1c</jats:sub>category as time‐varying covariate. At baseline in 1995, 806 subjects (male sex, 49.3%; age, mean±standard deviation, 62.70±11.08 years) were included. During follow‐up, 123 subjects experienced at least 1<jats:styled-content style="fixed-case">CVD</jats:styled-content>event (48 suffered myocardial infarction, 68 stroke, and 7 both). Among subjects with HbA<jats:sub>1c</jats:sub>≥6.5% (≥48 mmol/mol), those with the Hp 2‐2 genotype did not show an elevated risk of incident<jats:styled-content style="fixed-case">CVD</jats:styled-content>compared with those with other genotypes (age‐ and sex‐adjusted hazard ratio [95%<jats:styled-content style="fixed-case">CI</jats:styled-content>], 0.47 [0.19, 1.13],<jats:italic>P</jats:italic>=0.092) and a null association was also observed in subjects with HbA<jats:sub>1c</jats:sub><6.5% (1.10 [0.75, 1.62],<jats:italic>P</jats:italic>=0.629) (<jats:italic>P</jats:italic>for interaction=0.082).</jats:p></jats:sec><jats:sec xml:lang="en"><jats:title>Conclusions</jats:title><jats:p xml:lang="en">Subjects with the Hp 2‐2 genotype and elevated HbA<jats:sub>1c</jats:sub>compared with subjects with other Hp genotypes and elevated HbA<jats:sub>1c</jats:sub>did not show increased<jats:styled-content style="fixed-case">CVD</jats:styled-content>risk.</jats:p></jats:sec>