PECAM1, COL4A2, PHACTR1, and LMOD1 Gene Polymorphisms in Patients with Unstable Angina

Coronary artery disease (CAD) is a syndrome resulting from myocardial ischaemia of heterogeneous pathomechanism. Environmental and genetic factors contribute to its development. Atherosclerotic plaques that significantly narrow the lumen of coronary arteries cause symptoms of myocardial ischaemia. Acute coronary incidents are most often associated with plaque rupture or erosion accompanied by local activation of the coagulation system with thrombus formation. Plaque formation and stability are influenced by endothelial function and vascular smooth muscle cell function. In this study, we investigated the association between polymorphisms in genes affecting endothelial and vascular smooth muscle cell (VSMC) function and the occurrence of unstable angina pectoris. The aim of this study was to evaluate the association between the PECAM1 (rs1867624), COL4A2 (rs4773144), PHACTR1 (rs9349379) and LMOD1 (rs2820315) gene polymorphisms and the risk of unstable angina. The study included 232 patients with unstable angina diagnosed on the basis of clinical symptoms and coronary angiography and 144 healthy subjects with no significant coronary lumen stenosis at coronary angiography. There were no statistically significant differences in the distribution of COL4A2 rs4773144 and PECAM1 rs1867624 gene polymorphisms between patients with unstable angina and control subjects. In patients with unstable angina, there was an increased frequency of PHACTR1 rs9349379 G allele carriers (GG and AG genotypes) (GG+AG vs. AA, OR 1.71; 95% CI 1.10–2.66, p = 0.017) and carriers of the LMOD1 rs2820315 T allele (TT and CT genotypes) (TT+CT vs. CC, OR 1.65; 95% CI 1.09–2.51, p = 0.019) compared to the control group. The association between these alleles and unstable angina was confirmed by multivariate logistic regression analysis, in which the number of G (PHACTR1 rs9349379) and T (LMOD1 rs2820315) alleles was an independent risk factor for unstable angina. The results suggest an association between PHACTR1 rs9349379 and LMOD1 rs2820315 polymorphisms and the risk of unstable angina.

Cardiovascular computed tomography imaging for coronary artery disease risk: plaque, flow and fat

Cardiac imaging is central to the diagnosis and risk stratification of coronary artery disease, beyond symptoms and clinical risk factors, by providing objective evidence of myocardial ischaemia and characterisation of coronary artery plaque. CT coronary angiography can detect coronary plaque with high resolution, estimate the degree of functional stenosis and characterise plaque features. However, coronary artery disease risk is also driven by biological processes, such as inflammation, that are not fully reflected by severity of stenosis, myocardial ischaemia or by coronary plaque features. New cardiac CT techniques can assess coronary artery inflammation by imaging perivascular fat, and this may represent an important step forward in identifying the ‘residual risk’ that is not detected by plaque or ischaemia imaging. Coronary artery disease risk assessment that incorporates clinical factors, plaque characteristics and perivascular inflammation offers a more comprehensive individualised approach to quantify and stratify coronary artery disease risk, with potential healthcare benefits for prevention, diagnosis and treatment recommendations. Furthermore, identifying new biomarkers of cardiovascular risk has the potential to refine early-life prevention strategies, before atherosclerosis becomes established.

Clinico-pathophysiological considerations in coronary microvascular disorders

Around half of the patients undergoing an elective coronary angiogram to investigate typical stable angina symptoms are found to have non-obstructive coronary arteries (defined as < 50% stenosis). These patients are younger with a female predilection. While underlying mechanisms responsible for these presentations are heterogeneous, structural and functional abnormalities of the coronary microvasculature are highly prevalent. Thus, coronary microvascular dysfunction (CMD) is increasingly recognised as an important consideration in patients with non-obstructive coronary arteries. This review will focus on primary coronary microvascular disorders and summarise the four common clinical presentation pictures which can be considered as endotypes - Microvascular Ischaemia (formerly “Syndrome X”), Microvascular Angina, Microvascular Spasm, and Coronary Slow Flow. Furthermore, the pathophysiological mechanisms associated with CMD are also heterogenous. CMD may arise from an increased microvascular resistance, impaired microvascular dilation, and/or inducible microvascular spasm, ultimately causing myocardial ischaemia and angina. Alternatively, chest pain may arise from hypersensitivity of myocardial pain receptors rather than myocardial ischaemia. These two major abnormalities should be considered when assessing an individual clinical picture, and ultimately, the question arises whether to target the heart or the pain perception to treat the anginal symptoms.

Anaesthetic preconditioning and its role in protecting patients at risk of myocardial ischaemia

Ischaemic preconditioning is a phenomenon where prior minor ischaemic events allows organs to better withstand further episodes of ischaemia. Preconditioning downgrades the effects of ischaemia from necrosis to apoptosis to cell survival. It occurs in a wide variety of tissues, but it is most widely studied in the heart, and it occurs after a range of stimuli including hypoxia and the use of volatile anaesthetic agents. In this article, we look at the basic science, mechanisms, and potential uses of preconditioning.

Nephrological Aspects of Metabolic Syndrome in Patients with Chronic Kidney Disease on Peritoneal Dialysis with Different Clinical Variants of Coronary Heart Disease

The purpose of the study was to identify the components of the metabolic syndrome most characteristic of different clinical variants of ischemic heart disease in patients with chronic kidney disease on peritoneal dialysis. Materials and methods. 114 patients took part in the study. The average duration of peritoneal dialysis therapy was 53 months. Clinical variants of ischemic heart disease were determined by angina attacks, by painless myocardial ischemia detected by ECG-load cycle ergometer test, by increasing phenomena of ischemic dilated cardiomyopathy (diastolic dysfunction, calcification and atheromatosis of aorta and heart valves) by echocardiographic study in dynamics and by the previous myocardial infarction episodes. All patients were accordingly divided into 5 clinical groups, one of which was patients with no evidence of coronary heart disease (comparison group). The data were processed using the SPSS 19.0 for Windows statistical software package. Results and discussion. Considering different components of metabolic syndrome: body weight, arterial hypertension, dyslipidemia, the highest body mass index in patients on peritoneal dialysis was found in the group of patients suffering from ischemic dilated cardiomyopathy. High-density lipoproteins were lowest in the group of patients who underwent myocardial infarction. Hypertriglyceridemia was most pronounced in the group of patients with painless myocardial ischaemia. Low-density lipoproteins were highest in the group of patients with stable angina pectoris. Mean arterial pressure was highest in the group of patients with stable angina and in the group of patients with painless myocardial ischaemia. Conclusion. The highest number of patients with metabolic syndrome was found in the groups of patients with non-painful myocardial ischemia and ischemic dilated cardiomyopathy (67% and 51% respectively). In the group of patients with non-painful myocardial ischaemia (high acute coronary risk group), metabolic syndrome was diagnosed by four features: visceral obesity, raised blood sugar, arterial hypertension, raised very low density of lipoproteins and triglycerides. In the group of patients with ICDMP (group of patients with severe diastolic heart failure), metabolic syndrome was diagnosed by three features: visceral obesity, elevated blood sugar and low density lipoproteins. Thus, a vector for further research may be to investigate the effect of complexly corrected components of the metabolic syndrome on the occurrence of acute coronary risks or progression of chronic heart failure in patients with chronic kidney disease on peritoneal dialysis

259 Incidence, predictors, and prognostic role of complications occurring during intracoronary provocative test with acetylcholine in patients with myocardial ischaemia and non-obstructive coronary arteries

Aims Coronary provocative test with acetylcholine (ACh) is of utmost importance and increasingly used in patients with myocardial ischaemia and non-obstructive coronary arteries. However, data on safety, predictors, and prognostic role of complications during intracoronary provocative testing are scarce. We aimed at assessing the safety of ACh provocative test in patients with myocardial ischaemia and non-obstructive coronary arteries. Moreover, we evaluated the predictors and the prognostic implications of complications occurring during the provocative test. Methods and results We prospectively enrolled consecutive patients undergoing intracoronary ACh provocative test for suspected myocardial ischaemia with angiographic evidence of non-obstructive coronary arteries. Complications during the ACh test were collected. Occurrence of major adverse cardiac events (MACE), arrhythmic events at 24-h ECG dynamic Holter monitoring and angina status were assessed at follow-up. We enrolled 310 patients [mean age 60.6 ± 11.9; 169 (54.5%) chronic coronary syndromes (CCS) and 141 (45.5%) with myocardial infarction and non-obstructive coronary arteries (MINOCA)]. The overall incidence of complications was low (9%) with a similar incidence in MINOCA and CCS [10 (7.1%) vs. 18 (10.7%), P = 0.276, respectively]. At multivariate logistic regression analysis, a previous history of paroxysmal atrial fibrillation [odds ratio (OR): 12.324, confidence interval (CI): 95% (4.641–32.722), P = 0.015] and moderate/severe diastolic dysfunction [OR: 3.827, 95% CI (1.296–11.304), P = 0.015] were independent predictors for occurrence of complications. The occurrence of complications was not associated with a worse clinical outcome at follow-up (median follow-up 22 months) in terms of both MACE, arrhythmic events and angina burden. Conclusions Intracoronary provocative testing with ACh test is safe in patients with myocardial ischaemia and non-obstructive coronary arteries (including MINOCA patients). History of paroxysmal atrial fibrillation and moderate/severe diastolic dysfunction predicted the occurrence of complications during ACh test. However, occurrence of complications did not portend a worse prognosis at follow-up in terms of MACE, arrhythmic events, and angina burden.