Overview
Atherosclerosis and its complications are a global problem. There are several widely known and proven risk factors that promotes atherogenesis in the majority of patients. However, significant proportion of apparently healthy and young patients with cardiovascular disease but yet without recognized atherogenesis promoting risk factors can be observed in clinical practice. It highlights the need of new risk markers for early atherosclerosis diagnostics to prevent serious cardiovascular complications in these patients and in population in general. The interest in the negative impact of genetic variance, gene regulation on atherogenesis is growing. Therefore the purpose of this study is to analyze the impact of genetic variance and microRNA expression on early atherosclerosis development in the population of young, apparently healthy patients with coronary atherosclerosis. The primary hypothesis is that the group of patients with premature atherosclerosis have common genetic variations promoting early atherosclerosis development. The secondary hypothesis is that specific circulating microRNA expression (miR-126, miR-145 and miR-155) correlate with plaque lipid core by near infrared spectroscopy (NIRS) analysis.
Description
Patients with early atherosclerosis undergoing coronary angiography or percutaneous transluminal coronary angioplasty (PTCA) at Pauls Stradins Clinical University Hospital, Latvia will be included in the early atherosclerosis registry. Patients without explicit atherosclerosis risk factors undergoing coronary angiography or PTCA will undergo near-infrared spectroscopy imaging and blood samples for microRNA expression evaluation and genetic analysis will be obtained.
Exclusion criteria:
- Refusion to participate in the registry
- Men ≥55 years and women ≥65 years
- Coronary artery atherosclerosis < 50% or ≥50% without proven ischaemia and planned revascularization or no history of coronary artery revascularization
Exclusion criteria for additional genetic analysis and intravascular coronary imaging:
- Diabetes mellitus
- Serum total cholesterol ≥ 7 mmol/l and/or LDL ≥ 5 mmol/l
- Family hypercholesterolemia
- Positive family history of cardiovascular disease (myocardial infarction, sudden cardiac death or cardiovascular disease of first-degree relatives at a young age - men <55 years, women <65 years)
- ≥20 pack years of smoking
- Malignant or resistant hypertension ≥ 10 years
- Body mass index ≥40 kg/m2
At the time of recruitment demographic characteristics, medical and family history, anthropometric parameters, smoking status, history of other risk factors and daily used medications will be recorded and venous blood samples will be obtained.
In obtained venous blood samples study researchers will evaluate biochemistry analysis which includes high-density and low-density lipoprotein cholesterols, total cholesterol, triglycerides, alanine aminotransaminase, aspartate aminotransferase, bilirubin, creatine kinase, glucose and glycated haemoglobin levels. Genetic analysis will include sequencing of the four major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9 and LDLRAP1). microRNA (miR)-126, miR-145 and miR-155 expression will be evaluated in all venous blood samples.
Patients undergoing repeated coronary angiography or PTCA will undergo intravascular imaging
- near-infrared spectroscopy to determine coronary plaque lipidic tissue content.
Follow-up phone calls will be performed after 6, 12 and 24 months. In the follow-up study researchers will obtain additional information on study participants including smoking status, daily used medications and anthropometric parameters.
Eligibility
Inclusion criteria:
- Signed informed consent
- Early atherosclerosis defined as coronary atherosclerosis in men aged <55 years and women <65 years
- Coronary artery atherosclerosis with angiographically proven coronary vessel luminal stenosis ≥ 50% and ischaemia
- Coronary artery atherosclerosis with planned revascularization
- History of coronary artery revascularization (PTCA or coronary artery bypass surgery)
- Coronary vessel suitable for NIRS pullback
Exclusion criteria:
- Diabetes
- Total cholesterol ≥7 mmol/l and/or LDL ≥ 5 mmol/l
- family hypercholesterolemia
- positive family history of early cardiovascular disease (myocardial infarction, sudden cardiac death or cardiovascular disease of first degree relatives at young age - men <55 years, women <65 years)
- malignant or resistant hypertension ≥ 10 years
- body mass index ≥40 kg/m 2 )
- 20 or more pack years of smoking