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Published on: June 2, 2022
Serum Calcification Propensity Is Increased in Myocardial Infarction and Hints at a Pathophysiological Role
Rik Mencke1, Lawien Al Ali2, Marie-Sophie L Y de Koning2
1Department of Pathology and Medical Biology, Division of Pathology (R.M., H.v.G., J.L.H.), University Medical Center Groningen, the Netherlands.
Insights
Patients with ST-segment-elevated myocardial infarction show increased serum calcification propensity, measured by calciprotein particle maturation time (T50). This propensity is higher in women and linked to lipid profiles, not traditional risk factors.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Nephrology
Background:
- Vascular calcification is a significant predictor of mortality in cardiovascular disease patients.
- Calciprotein particles are implicated in vascular calcification, with their maturation time (T50) reflecting serum calcification propensity.
- Understanding T50's role in ST-segment-elevated myocardial infarction (STEMI) is crucial for cardiovascular risk assessment.
Purpose of the Study:
- To compare T50 between STEMI patients and controls.
- To investigate the association of T50 with cardiovascular risk factors and outcomes in STEMI patients.
- To explore the relationship between T50, endothelial function markers (nitrite), and lipid profiles.
Main Methods:
- T50 was measured using nephelometry in STEMI patients (GIPS-III trial) and general population controls (PREVEND).
- Associations between T50 and left ventricular ejection fraction, infarct size, reintervention rates, and serum nitrite were assessed.
- Follow-up for ischemia-driven reintervention was conducted over 5 years.
Main Results:
- STEMI patients exhibited significantly lower T50 (higher calcification propensity) than controls (289±63 vs. 338±56 minutes, P<0.001).
- In STEMI patients, lower T50 correlated with female sex, lower blood pressure, and a more favorable lipid profile (lower LDL, higher HDL).
- Ischemia-driven reintervention showed interaction with T50 and sex, with correlations differing between men and women.
Conclusions:
- STEMI patients have increased serum calcification propensity compared to the general population, with a greater impact in women.
- T50 is largely independent of traditional risk factors like blood pressure and nitrite levels.
- The association of lower T50 with a favorable lipid profile suggests distinct pathophysiological pathways in myocardial infarction involving calcification and lipid stress.
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 (T50) of calciprotein particles provides a measure of serum calcification propensity. We compared T50 between patients with ST-segment-elevated myocardial infarction and control subjects and studied the association of T50 with cardiovascular risk factors and outcome.
Methods:
T50 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 T50 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 T50 (ie, higher serum calcification propensity) compared with controls (T50: 289±63 versus 338±56 minutes; P<0.001). In patients with ST-segment-elevated myocardial infarction, lower T50 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 T50 and sex (P=0.005), indicating a correlation between ischemia-driven reintervention and T50 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 T50 to be orthogonal to traditional cardiovascular disease risk factors. Lower T50 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.
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