Serum Calcification Propensity Is Increased in Myocardial Infarction and Hints at a Pathophysiological Role Independent of Classical Cardiovascular Risk Factors
Rik Mencke, Lawien Al Ali, Marie-Sophie L.Y. de Koning, Andreas Pasch, Magdalena Minnion, Martin Feelisch, Dirk J. van Veldhuisen, Iwan C.C. van der Horst, Ron T. Gansevoort, Stephan J. L. Bakker, Martin H. de Borst, Harry van Goor, Pim van der Harst, Erik Lipšic, Jan‐Luuk Hillebrands
Abstract
BACKGROUND: Vascular calcification is associated with increased mortality in patients with cardiovascular disease. Secondary calciprotein particles are believed to play a causal role in the pathophysiology of vascular calcification. The maturation time (T 50 ) of calciprotein particles provides a measure of serum calcification propensity. We compared T 50 between patients with ST-segment–elevated myocardial infarction and control subjects and studied the association of T 50 with cardiovascular risk factors and outcome. METHODS: T 50 was measured by nephelometry in 347 patients from the GIPS-III trial (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction: a Randomized Controlled Trial) and in 254 matched general population controls from PREVEND (Prevention of Renal and Vascular End-Stage Disease). We also assessed the association between T 50 and left ventricular ejection fraction, as well as infarct size, the incidence of ischemia-driven reintervention during 5 years of follow-up, and serum nitrite as a marker of endothelial dysfunction. RESULTS: Patients with ST-segment–elevated myocardial infarction had a significantly lower T 50 (ie, higher serum calcification propensity) compared with controls (T 50 : 289±63 versus 338±56 minutes; P <0.001). In patients with ST-segment–elevated myocardial infarction, lower T 50 was associated with female sex, lower systolic blood pressure, lower total cholesterol, lower LDL (low-density lipoprotein) cholesterol, lower triglycerides, and higher HDL (high-density lipoprotein) cholesterol but not with circulating nitrite or nitrate. Ischemia-driven reintervention was associated with higher LDL ( P =0.03) and had a significant interaction term for T 50 and sex ( P =0.005), indicating a correlation between ischemia-driven reintervention and T 50 above the median in men and below the median in women, between 150 days and 5 years of follow-up. CONCLUSIONS: Serum calcification propensity is increased in patients with ST-segment–elevated myocardial infarction compared with the general population, and its contribution is more pronounced in women than in men. Its lack of/inverse association with nitrite and blood pressure confirms T 50 to be orthogonal to traditional cardiovascular disease risk factors. Lower T 50 was associated with a more favorable serum lipid profile, suggesting the involvement of divergent pathways of calcification stress and lipid stress in the pathophysiology of myocardial infarction.