Heart rate and other risk factors in outpatients with stable coronary artery disease in Latvia
The aim of the study was to characterise coronary artery disease (CAD) outpatients in Latvia by risk factors (RF) including heart rate (HR), physical examination data, clinical data and treatment. Twelve practitioners had each examined and questioned 6 to 12 patients with established CAD (n = 120). The most frequent cardiovascular (CV) RF and co-morbidity were dyslipidemia (94.2%) and hypertension (78.3%), respectively. Prevalence of increased resting HR (≥70 bpm) was 35.9% and 33.6%, when measured by pulse palpation and electrocardiography, respectively. Regarding other RFs, prevalence of treated but insufficiently controlled blood pressure 140/90 mmHg, total cholesterol 1 > 5 mmol/l and triglycerides > 1.7 mmol/l was 25.8%, 30.1% and 33.3%, respectively. Aspirin, statins and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers were used in 96.7%, 94.2% and 85.0% of cases, respectively. Beta blockers were used in 81.7% of cases. Average daily doses of most frequently used β blockers (metoprolol and bisoprolol) were 32% and 53% from target doses, respectively. In three cases β blockers were combined with ivabradin. Our results suggest that practitioners follow guidelines and consider CV prevention by treating CAD patients. Our data identified, however, unused potential for better control of increased HR by higher doses and combinations of HR-reducing agents.
Current state of angina treatment in the outpatient population and heart rate monitoring survey in Latvia (RELITY LATVIA)
The aim of the REALITY Latvia survey was to accumulate information about treated stable angina outpatients regarding their characteristics, heart rate (HR), treatment, and quality of life. Thirty cardiologists were involved with 1-15 patients each. In total, data about 300 patients were obtained. Patients were examined and questioned during one visit. A high HR was defined above 70 beats per minute (bpm), in accordance to recent evidence. Mean HR was 70.3 ± 11.3 bpm and 45% of patients had HR above 70 bpm. The opinion of practitioners regarding HR differed. For example, a HR level within the range 70-80 bpm was perceived by cardiologists as "normal", "borderline high" and "high". The mean target HR that physicians wanted to achieve was 60.1 ± 4.7 bpm. Beta blockers were used in 91% of cases. The more widely used beta blockers were metoprolol (47%) and bisoprolol (35%) in mean daily doses 69.7 ± 30.1 mg and 5.3 ± 2.0 mg, respectively. REALITY Latvia data suggest that, despite wide use of beta blockers, HR control in stable angina patients is insufficient. This is caused by insufficient understanding of HR as a treatment target by physicians and use of beta blockers in suboptimal dosages.
Relation of the Leu40Arg variant of glycoprotein IIIA to personal and family history of myocardial infarction
GPIIb/IIIa fibrinogen receptor is a key element of the thrombotic pathway. In this study, we investigated the possible relation of PlA1/A2 polymorphism (1565T>C; Leu33Pro) and a rare 1586T>G (Leu40Arg) variation of GPIIIa gene to personal and family history of myocardial infarction (MI) among 601 patients with angiographically confirmed coronary heart disease. Four hundred and fifteen patients had MI and 94 of individuals reported family history of premature MI. The Arg40 (1586G) variant (n = 4) was present exclusively in MI-patients and significantly correlated with a family history of premature MI (P = 0.013), whereas the Pro33 (1565C; PlA2) allele (n = 204) was similarly prevalent among different groups of patients. These data indicate the importance of the Arg40 variant but do not support a significant role of Pro33 allele in susceptibility to MI.
The aim of the study was to evaluate control of heart rate (HR) and other risk factors (RF) over athree-year period in coronary artery disease (CAD) outpatients in Latvia. Patients (n = 120) were examined and questioned at baseline time and annually (four times in total). Increased resting HR (≥70 bpm) when measured by palpation was present in 35.8% of cases at baseline time, 35.6%, 29.8% and 35.1% of cases at Y1, Y2 and Y3, respectively; when measured by electrocardiography: in 33.6% (baseline), 36.8% (Y1), 26.7% (Y2), 33.7% (Y3) of cases. The proportion of patients with increased HR did not significantly change in Y1–Y3 vs baseline. Systolic blood pressure was lower in Y1 and Y3 vs baseline (P = 0.005 and P = 0.003, respectively). The proportion of patients with increased blood pressure (≥140/90 mmHg) was lower in Y1, Y2 and Y3 than at baseline (P = 0.018, P = 0.030 and P = 0.017, respectively). The proportion of patients with a decreased level of high density lipoprotein cholesterol (<1.2 mmol/l for women and <1.0 mmol/l fom men) was lower in Y1–Y3 compared to baseline (P < 0.001). A substantial (about one-third) and stable proportion of patients with increased HR≥70 bpm over the three-year period in the examined sample of treated CAD patients indicates that there is a need for better control of this RF.
Analysis of Polymorphisms at the Adiponectin Gene Locus in Association with Type 2 Diabetes, Body Mass Index and Cardiovascular Traits in Latvian Population
Despite the number of recently conducted studies seeking to determine the association between genetic variants of adiponectin gene and susceptibility to type 2 diabetes (T2D) and increased body mass index (BMI), the results obtained are often inconsistent. To determine the impact of common polymorphisms in promoter and coding regions of adiponectin gene on these conditions in Latvian population, we selected ten SNPs (rs2241767, rs1501299, rs3777261, rs16861210, rs2241766, rs822396, rs182052, rs17300539, rs16861194, rs266729) based on haploblock structure and previously reported association studies. The selected SNPs were screened in a study group of 835 participants from the Genome Data Base of Latvian Population and mainly consisted of patients with T2D and coronary heart disease. None of the individual polymorphisms were significantly associated with T2D status or BMI when analysed using logistic or linear regression and adjusted for gender, age and other significant covariates. Frequency of rs2241766 T allele homozygotes however was significantly increased in T2D patients compared to controls (uncorrected P = 0.007). When analysed with other traits, the rs182052 G allele was found to be less frequent in patients suffering from myocardial infarction (P = 0.02; OR = 0.76, CI95% [0.61-0.92]) compared to others. Haplotype analysis revealed significant association of one haplotype with atrial fibrillation (uncorrected P = 0.01). In summary, we conclude that SNPs in adiponectin gene are unlikely to represent the risk for T2D, but may be involved in pathogenesis of CHD in the Latvian population.
Long-term Clinical Results for Randomised Comparison of Paclitaxel-eluting versus Bare-metal Stents in Unprotected Left Main Coronary Artery Disease
To optimise percutaneous coronary intervention (PCI) strategy for unprotected left main (ULMCA) disease we performed a randomised study: IVUS-guided bare metal stent (BMS) versus paclitaxel-eluting stent (PES) implantation after lesion pre-treatment with cutting balloon (CB) for unprotected LM lesions. The purpose of this randomized study was to evaluate six-month and three-year clinical results. Several recent publications have demonstrated good short- and midterm outcomes in patients with left main artery disease after stent implantation. However, data on long-term comparison of BMS and PES for LM lesions are limited. Patients with left main coronary artery disease enrolled at Latvian Centre of Cardiology were randomly assigned to either BMS (n = 50) or PES implantation (n = 53). All interventions were IVUS-guided and CB pre-treatment before stenting was performed in all patients. All patients were scheduled for six-month and three-year follow-up. The primary endpoint was major adverse cardiac events (MACE) defined as death, Q wave myocardial infarction or target lesion revascularisation (TLR). Baseline clinical and procedural characteristics were comparable in both groups. At six months, the MACE-free survival rate was 70% in BMS and 87% in PES patients (P < 0.05). At three years, MACE occurred in 18 patients (36.0%) in the BMS and seven patients (13.2%) in the PES group (P < 0.05). The current study demonstrates the benefit of IVUS guided paclitaxel-eluting stent implantation after cutting balloon pre-treatment in left main coronary artery disease over bare metal stent implantation at six months and three years.
Comparison of Intravascular Imaging and Quantitative Coronary Angiography to Evaluate Neointimal Proliferation after Complex Lesion Stenting
Unlike quantitative coronary angiography (QCA), intravascular imaging methods allow direct visualisation of the arterial wall. Our goal was to determine several intravascular ultrasound (IVUS) and optical coherence tomography (OCT) parameters of neointimal proliferation and stent endothelisation after complex lesion intervention compared to QCA. We examined 261 patients who had underwent percutaneous intervention with bare metal (BMS) or drug eluting stent (DES) implantation for complex coronary lesions and had IVUS or OCT images at six-month follow-up. Percent diameter stenosis (QCA) was 25.2 ± 16.0 in BMS vs 21.7 ± 17.4 in DES (P < 0.05). Percent neointimal volume obstruction (IVUS) was 19.5 ± 14.4 in BMS vs. 5.8 ± 7.7 in DES (P < 0.001). A moderate correlation was observed between QCA and IVUS with an r value of 0.384 overall, 0.472 for BMS and 0.416 for DES (P < 0.001 for all). In patients with chronic total occlusions (n = 161) QCA was similar in BMS and DES patients (P > 0.05) while IVUS showed less neointima in DES (P < 0.05). Total number of uncovered stent struts per OCT image was 0.4 ± 0.8 while per IVUS image 1.2 ± 1.5 (P < 0.001). In conclusion, angiographic indexes correlate with volumetric intravascular parameters. Although IVUS was more sensitive than QCA to assess neointimal proliferation, the assessment of stent endothelisation was more precise using OCT.
Familial hypercholesterolemia (FH) is one of the most common single gene disorders, which is mostly inherited as an autosomal dominant trait. The physical signs of FH are elevated low density lipoprotein cholesterol (LDL-C), elevated total cholesterol (TC) levels and tendon xantomas. Identification and early treatment of affected individuals is desirable and in lack of physical symptoms DNA-based diagnosis provides confirmation of diagnosis and enables early patient management. The majority of FH cases are caused by mutations in four genes (APOB, LADLR, PCSK9, and LDLRAP1). There are commercial kits available for testing of the 20 most common FH causing mutations, but the spectrum of disease-causing mutations is quite diverse in various populations and these tests cover only a minority of disease-causing genetic variants. There is therefore a need to determine the full spectrum of mutations in LDLR, APOB, PCSK9, and LDLRAP1 genes in each population. Here we report mutations found in 16 patients with suspected FH in a sample from the Genome Database of the Latvian population enrolled at the Latvian Centre of Cardiology. We used the next generation sequencing approach to determine the full spectrum of mutations in coding regions of LDLR, APOB, PCSK9, and LDLRAP1. In total we found 22 missense mutations, from which only rs5742904 (Arg3527Gln) in APOB gene had been previously described as a FH-causing mutation confirming FH in one patient. Possible FH-causing mutations however, were identified in the majority of patients. The conclusion is that the most commonly employed commercial mutation panel is not sufficient for diagnosis of FH patients and NGS can help to identify FH-causing mutations in the Latvian population.