Diabetes and Obesity

Obesity and Diabetes are leading causes of cardiovascular disease and mortality. They are closely linked because of insulin resistance. Hypertension and dyslipidaemia together with poor exercise drive atherosclerosis. Early treatment of blood sugar, dyslipidaemia and hypertension reverse the atherosclerosis process. Bariatric surgery and low calorie diets have in recent years been shown to reverse or improve blood sugars lipids and blood pressure. The risk of premature myocardial infarction and death should no longer be the desired outcome.

Pcsk9 is associated with severity of coronary artery lesions in male patients with premature myocardial infarction

Background Proprotein convertase subtilisin/kexin type 9 (Pcsk9) correlated with incidence and prognosis of coronary heart disease. However, it is unclear whether Pcsk9 contributed to coronary artery lesion severity in patients with premature myocardial infarction (PMI). The present study investigated associations between Pcsk9 and coronary artery lesion severity in PMI patients who underwent coronary angiography (CAG). Methods This prospective cohort study included young men (age ≤ 45 years, n = 332) with acute MI who underwent CAG between January 2017 and July 2019. Serum Pcsk9 levels and clinical characteristics were evaluated. SYNTAX scores (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) were calculated to quantify coronary artery lesions. Results Serum Pcsk9 levels were positively associated with SYNTAX scores (r = 0.173, P < 0.05). The diagnostic cutoff value of PSCK9 level was 122.9 ng/mL, yielding an area under the curve (AUC) of 0.63, sensitivity 81%, and specificity 40%. Serum Pcsk9, LDL-C, Apob, NT-proBnp, CK level, and diabetes history were independent predictors of high SYNTAX scores (P < 0.05). After stratifying by serum LDL-C level (cutoff = 2.6 mmol/L), medium-high Pcsk9 levels had increased risk of high SYNTAX scores in patients with high LDL-C (P < 0.05), and higher serum Pcsk9 levels had increased risk of major adverse cardiac events (MACE) after adjusting for confounding factors (P < 0.05). Conclusion Serum Pcsk9 levels correlates with severity of coronary artery lesion in PMI patients and may serve as a biomarker for severity of coronary artery stenosis in this patient population, which may contribute to risk stratification.

P721Shear stress induced unfolding of von willebrand factor may be involved in the premature development of myocardial infarction

Background Normally, von Willebrand factor (vWF) becomes highly reactive with platelets upon unfolding into a fibrillar conformation at critical shear rate (more than 5000 s–1), that may occur in stenotic arteries. At shear rates below critical value (1200–1300 s–1), which occur in intact coronary arteries, normally there is no conformational rearrangement of vWF. Pathologic unfolding of vWF at shear rates below critical value may increase a risk of the development of coronary thrombosis. There is little information on the role of shear stress induced conformational rearrangement of vWF in the development of myocardial infarction in young individuals. Purpose To investigate vWF-dependent platelet adhesion of patients with premature myocardial infarction at shear rates below critical value (1200–1300 s–1). Methods Using a microfluidic system, we measured platelet adhesion to a fibrinogen-coated optical surface at shear rates of 1200–1300 s–1 during 10 minutes. We assessed platelet-rich plasma of 8 male persons 40–52 years old, who had previous myocardial infarction at the age of 34–39. The control group comprised 6 healthy male volunteers 30–55 years old. We compared the intensity of scattered laser light measured in volts (V) at 10th minute. To study vWF-dependent platelet adhesion, we blocked GPIb receptor with monoclonal antibody to inhibit platelet interaction with vWF. To compare the intensity of vWF-dependent platelet adhesion with normally occurring adhesion to fibrinogen, we blocked GPIIb/IIIa receptor with monoclonal antibody. Results The inhibition of GPIb vWF-receptor decreased platelet adhesion to fibrinogen surface at shear rates of 1200–1300 s–1 by 17.8±4.7% in healthy volunteers and by 92±2.8% in persons with premature myocardial infarction (p<0.05). Inhibition of GPIIb/IIIa receptor decreased platelet adhesion by 91.5±3.8% in healthy volunteers and by 97.3±3.2% in persons with premature myocardial infarction. Conclusion Pathologic unfolding of vWF at shear rates below critical value may be involved in the development of premature myocardial infarction. Acknowledgement/Funding This work was supported by the grant of the Russian Science Foundation (project #16-15-10098)