Randomized Pilot Trial on Optimal Treatment Strategy, Myocardial Changes, and Prognosis of Patients with Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA).

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains an unresolved challenge. Many different diagnostic approaches are often required to diagnose, confirm, and evaluate MINOCA. The prevalence can be as high as 13% of all acute myocardial infarction patients, indicating that this condition is not rare. At this time, there have been no completed randomized clinical trials involving MINOCA patients, and a better understanding of the mechanisms and management of these patients is important. This exploratory analysis seeks to find possible etiologic factors, the value of novel biomarkers, and the effect of different treatment strategies in patients with MINOCA. METHODS: This prospective randomized pilot trial will include 150 patients with MINOCA. A thorough clinical, laboratory, and imaging evaluation will be performed, including novel biomarkers and modern imaging techniques (heart magnetic resonance imaging and noninvasive testing). The duration of the enrollment is 18 months, and duration of the follow-up is 12 months from the enrollment of the first patient. RESULTS: The trial is registered under www.clinicaltrials.gov: NCT04538924. The study is currently recruiting participants. CONCLUSIONS: Because MINOCA is not a benign disease, the results of the current investigation could inform future diagnostic and therapeutic strategies and enhance the understanding of MINOCA patients.

Trends in cardiovascular risk factor prevalence among Lithuanian middle-aged adults between 2009 and 2018.

BACKGROUND AND AIMS: The aim of the study was to estimate trends and differences in cardiovascular disease (CVD) risk factor prevalence among middle-aged men and women based on the data from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program between 2009 and 2018. METHODS: A community-based cross-sectional study included men aged 40-54 years and women aged 50-64 years without overt CVD. Nationally representative data comprised 110,370 Lithuanian adults (42.4% men and 57.6% women) examined in the period 2009-2018. Prevalences of major CVD risk factors, such as dyslipidaemia, arterial hypertension, diabetes mellitus, obesity, metabolic syndrome and smoking, were assessed. RESULTS: The study showed a significant drop in the prevalence of dyslipidaemia and TC levels among men (p = 0.030 and p < 0.001) and no significant change among women (p = 0.594 and p = 0.799). The prevalence of AH significantly decreased in both gender groups (p < 0.001 in women and p < 0.001 in men). Obesity rates declined among women while it remained constant among men (p < 0.001 and p = 0.100 respectively). There was a significant decline among women and a significant increase among men in the prevalence of metabolic syndrome (p < 0.001 and p = 0.016 respectively). The prevalence of diabetes increased until 2013, after which it started decreasing in the whole group (p = 0.005). The study showed a significant increase in the percentage of smoking women (p < 0.001), although the number of smoking men remained much higher (about 40%) (p < 0.001). CONCLUSIONS: In our observational study, we have documented a high prevalence of all CVD risk factors in 2009 with a slight decrease during the period in most prevalence rates, except in dyslipidaemia and smoking levels.

Autosomal recessive hypercholesterolemia: Case report.

INTRODUCTION: Autosomal recessive hypercholesterolemia (ARH; OMIM #603813) is a very rare monogenic disorder affecting less than 1 in 1000,000 people and is characterized by very high levels of low-density lipoprotein cholesterol (LDL-C), leading to aggressive and premature atherosclerotic cardiovascular disease if left untreated. Lowering of LDL-C is the main target of the treatment. We report on a 29-year-old male patient born in nonconsanguineous Lithuanian family homo(hemi-)zygous for LDLRAP1 gene variant causing ARH. This variant is not present in population databases and, to our knowledge, has not been reported in scientific literature before. METHODS AND RESULTS: The earliest clinical sign, noticed at the age of 5 years, was painful and enlarging nodules on Achilles tendons. At the age of 10 years, xanthomas of the metacarpal joint area on both hands emerged. The first lipid panel was performed at the age of 12 years. In accordance with Dutch Lipid Clinic Network diagnostic criteria for familial hypercholesterolemia (FH), definite FH (type IIA hyperlipoproteinemia) was diagnosed and the treatment with cholestyramine 4 grams per day was initiated. As the patient was 15 years old, direct adsorption of low-density lipoprotein apheresis was started and repeated monthly. At the age of 20 years, along with lipoprotein apheresis, 10 mg of rosuvastatin daily intake was prescribed. At the age of 28 years, the dose of rosuvastatin was increased to 40 mg per day, and 10 mg of ezetimibe daily intake was added. At the age of 28 years, homozygous LDLRAP1 gene variant NM_015627.2:c.488A>C, NP_056442.2:p.(Gln163Pro) causing autosomal recessive hypercholesterolemia was determined by genetic testing. CONCLUSIONS: This case report implies that ARH, being an extremely rare disorder, is a severe disease. As there is limited routine testing, including genetic testing, patients suffering from both this disease and FH may remain undiagnosed. Cascade screening and genetic counseling differ for ARH as compared with FH, as the carrier of a pathogenic variant in the LDLRAP1 gene does not have marked total cholesterol and LDL-C elevations. However, genetic testing of the proband and their relatives is essential to evaluate the risk of development of FH and to provide prognosis as well as adequate, timely treatment. To improve the quality of life of patients with FH and prolong their life expectancy, national registries of FH and wider laboratory and genetic testing are undoubtedly necessary. A national FH screening program was set up in Lithuania, which helps to identify, monitor, and treat subjects with FH.

Lower than average HDL cholesterol efflux capacity in Lithuanian population.

BACKGROUND: The aim of our study was to evaluate high-density lipoprotein cholesterol (HDL-C) efflux capacity in healthy controls and patients with severe dyslipidemia. Evaluation of HDL function may be beneficial for better understanding of cardiovascular diseases, as well as for taking actions to minimize residual cardiovascular risk. METHODS: During 2016-2017 a total of 93 participants - 48 (51.6%) women and 45 (48.4%) men - were included in this cross-sectional study. Data of 45 (48.4%) participants with severe dyslipidemia (SD) and 48 (51.6%) controls without dyslipidemia was used for statistical analysis. Total lipid panel, concentration of lipoprotein (a) and apolipoproteins were measured, data about cardiovascular risk factors were collected and detailed evaluation of HDL-C quality was performed for all patients. RESULTS: Increased HDL-C concentration was associated with higher ApoA1 (r = 0.866 in controls, r = 0.63 in SD group), ApoA2 (r = 0.41 in controls, r = 0.418 in SD group) and LDL-C concentrations (r = - 0.412 in SD group), lower ApoE (r = - 0.314 in SD group) and TG concentrations (r = - 0.38 in controls, r = - 0.608 in SD group), lower ApoB/ApoA1 ratio (r = - 0.567 in control group), below average HDL-C efflux capacity (r = - 0.335 in SD group), lower BMI (r = - 0.327 in controls, r = - 0.531 in SD group) and abdominal circumference (r = - 0.309 in women with SD). Below-average HDL-C efflux capacity was found in 67.7% (N = 63) of participants. It was more often found among patients with normal weight or BMI 30-31 kg/m2. HDL-C efflux capacity was inversely associated with HDL-C concentration (r = - 0.228). CONCLUSION: Abnormal HDL function may be associated with residual cardiovascular risk in Lithuanian population.

Is the coronary artery calcium score the first-line tool for investigating patients with severe hypercholesterolemia?

BACKGROUND: Coronary artery calcium (CAC) is known as a reliable tool for estimating risk of myocardial infarction, coronary death, all-cause mortality and is even used to evaluate suitable asymptomatic patients. We therefore aimed to evaluate whether CAC scoring can be applied in the algorithm for clinical examination of patients with severe hypercholesterolemia (SH). METHODS: During the period of 2016-2017 a total of 213 asymptomatic adults, underwent computed tomography angiography to evaluate their CAC scoring. The sample consisted of 110 patients with SH and 103 age and sex matched controls without dyslipidemia and established cardiovascular disease. RESULTS: In total there were 79 (37.2%) subjects with elevated (≥25th) CAC percentiles. Out of them 47 (59.5%) had SH and 32 (40.5%) did not. CAC score did not differ between groups (SH (+) 140.30 ± 185.72 vs SH (-) 87.84 ± 140.65, p = 0.146), however there was a comparable difference in how the participants of these groups distributed among different percentile groups (p = 0.044). Gender, blood pressure, tabaco use, physical activity, family history of coronary artery disease and diabetes mellitus were not associated with CAC score (p > 0.05). There were no significant correlations between biochemical parameters and CAC percentiles except for increase in lipoprotein(a) (p = 0.038). Achilles tendon pathology, visceral obesity, body mass index and increased waist-hip ratio were not associated with CAC percentiles either (p > 0.05). CONCLUSIONS: CAC score is not associated with presence of SH. CAC score is not an appropriate diagnostic tool in the algorithm for clinical examination of patients with SH. Further larger studies are needed to support our findings.

Trends in Cigarette Smoking among Middle-Aged Lithuanian Subjects Participating in the Primary Prevention Program between 2009 and 2016.

Background and Objectives: The aim of the study was to evaluate trends in smoking among middle-aged men and women based on the data from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program between 2009 and 2016. Materials and Methods: A community-based cross-sectional study comprised 92373 Lithuanian adults (41.6% men and 58.4% women). We compared the prevalence of smoking, smoking cessation activity and smoking intensity by gender and age groups. Results: There was a statistically significant upward trend in the number of smoking subjects (average annual percent change (AAPC) 2.99%, p < 0.001). The number of smoking male subjects remained much higher than the number of smoking female subjects during the 2009-2016 period. The study showed a significant increase in the percentage of smoking quitters in the whole group (AAPC 7.22%, p < 0.001) and among men and women separately. There was no significant change in smoking intensity in groups of male and female smokers separately. Conclusions: The analysis showed that the prevalence of smoking in Lithuania is still increasing due to women smoking despite all the governmental tobacco control efforts to reduce it.

Achilles tendon ultrasonography - A useful screening tool for cardiovascular risk estimation in patients with severe hypercholesterolemia.

BACKGROUND AND AIMS: Achilles tendon lesions have long been associated with genetic defects in lipid metabolism and increased risk of cardiovascular diseases (CVD). With this study we aimed to evaluate the usefulness of Achilles tendon ultrasonography in identifying people at greater risk among subjects with severe hypercholesterolemia (SH) in a high-risk population. METHODS: During the period of 2016-2017 a total of 213 participants were enrolled in this case-control study. Data of 110 patients with SH and 103 age and sex matched controls without dyslipidaeplemia and established CVD was collected. RESULTS: Achilles tendinopathy (AT) was present in 42.7% of subjects with SH and in 29.1% of controls (p = 0.039). Stronger association between SH and AT was seen in women - 24.1% vs 2.0% (p = 0.001). SH increased odds of AT by 1.815 (95% CI, 1.028-3.206). Prevalence of AT was higher in males despite presence (SH+) or absence (SH-) of severe hypercholesterolemia (SH+ 60.7% vs 24.1%, SH- 55.8% vs 2.0%, p < 0.001). AT was associated with higher proportion of subjects exceeding normal mean values of TC (80.5% vs 52.9%, p = 0.001), LDL-C (76.6% vs 52.2%), TG (54.5% vs. 22.1%), ApoB (57.1% vs 22.2%), ApoE (44.0% vs 22.4%) levels and ApoB/ApoA ratio (46.1% vs 21.5%) (p = 0.001) and family history of premature coronary heart disease (CHD). CONCLUSIONS: AT is more prevalent among subjects with SH and is associated with higher levels of TC, TG, LDL-C, ApoB, ApoE, ApoB/ApoA ratio, family history of premature CHD. SH increases the odds of developing AT.

Lipid profile evaluation and severe hypercholesterolaemia screening in the middle-aged population according to nationwide primary prevention programme in Lithuania.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is a major cause of premature death in Lithuania where abnormal lipid levels are very common among middle-aged adults. The aim of this study was to evaluate lipid profile in middle-aged Lithuanians and perform population-based severe hypercholesterolaemia (SH) screening. METHODS: This study included men aged 40-54 and women aged 50-64 years without overt CVD, participating in the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention programme during the period 2009-2016. Lipidograms of 92,373 adults (58.4% women and 41.6% men) included in the database were analysed and screening for SH was performed. RESULTS: The mean levels of total cholesterol, LDL cholesterol (LDL-C) and triglycerides (TG) among participants were 6.08 mmol/l, 3.87 mmol/l, and 1.59 mmol/l, respectively. Any type of dyslipidaemia was present in 89.7%, and severe dyslipidaemia in 13.4% of the study population. 80.2% of adults without overt CVD had LDL-C ≥3 mmol/l. SH (LDL-C ≥6 mmol/l) was detected in 3.2% of study participants. Prevalence of SH decreased from 2.91% to 2.82% during the period 2009-2016 (p for trend = 0.003). LDL-C ≥6.5 mmol/l was observed in 1.5% of subjects while both LDL-C ≥6.5 mmol/l, and TG ≤ 1.7 mmol/l was found in 0.6% of subjects. CONCLUSIONS: SH was present in 3.2% of the middle-aged population without overt CVD. Slightly decreasing prevalence of SH was observed during the period 2009-2016 in Lithuania. Likely phenotypic familial hypercholesterolaemia was observed in 1.5% of middle-aged Lithuanians. Further clinical and genetic evaluation of people with SH is needed to detect familial forms of SH.

Establishing a national screening programme for familial hypercholesterolaemia in Lithuania.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is a widely underdiagnosed genetic disorder characterized by severely elevated levels of serum cholesterol and associated with premature mortality. Screening programmes and registries have been established worldwide to find and monitor patients with FH. The aim of this paper was to describe the approaches currently applied to identify patients with possible FH in Lithuania. METHODS: An electronic extraction tool was applied to the medical records of 92,373 subjects evaluated in primary care settings from 2009 to 2016, 1714 secondary prevention patients with early onset (<50 years) coronary heart disease (CHD) treated in tertiary care hospital from 2005 to 2016 and high-risk subjects in specialized cardiovascular prevention units. The electronic databases were screened for likely FH phenotype, which was described simply as LDL-C ≥6.5 mmol/l. RESULTS: Likely FH phenotype was observed in 1385 (1.5%) middle-aged Lithuanians, 290 (16.9%) people with premature CHD and 330 adults from high-risk subjects referred to specialized cardiovascular prevention units. A total of 2005 patients with likely phenotypic FH were included in the Lithuanian FH screening programme, covering about 15% of estimated FH cases in Lithuania. CONCLUSIONS: Screening for extremely elevated LDL-C levels in primary prevention database and additional enrolment of patients with premature CVD as well as high-risk subjects may be a valid way to set up a national FH screening programme. It is crucially important to identify and initiate the treatment of FH patients as early as possible to reduce high cardiovascular mortality in these patients.

Cardiovascular risk assessment of dyslipidemic middle-aged adults without overt cardiovascular disease over the period of 2009-2016 in Lithuania.

BACKGROUND: Cardiovascular mortality in Lithuania is extremely high and abnormal lipid levels are very common among Lithuanian adults. Dyslipidemia is one of the main independent risk factors for cardiovascular diseases (CVD) leading to high absolute CVD risk. The aim of this study was to assess CVD risk in dyslipidemic middle-aged subjects. METHODS: During the period of 2009-2016 a total of 92,373 people (58.4% women and 41.6% men) were evaluated. This study included men aged 40-54 and women aged 50-64 without overt CVD. RESULTS: Any type of dyslipidemia was present in 89.7% of all study population. 7.5% of dyslipidemic patients did not have any other conventional risk factors. Three and more risk factors were detected in 60.1% of dyslipidemic subjects. All analyzed risk factors, except smoking, were more common in dyslipidemic adults compared to subjects without dyslipidemia: arterial hypertension (55.8% vs. 43.3%, p < 0.001), diabetes (11.1% vs. 7.3%, p < 0.001), abdominal obesity (45.3% vs. 30.2%, p < 0.001), BMI ≥30 kg/m2 (35.8% vs. 23.7%, p < 0.001), metabolic syndrome (34.0% vs. 9.2%, p < 0.001), family history of coronary heart disease (26.3% vs. 23.1%, p < 0.001), unbalanced diet (62.5% vs. 52.9%, p < 0.001) and insufficient physical activity (52.0% vs. 44.2%, p < 0.001). The prevalence of all evaluated risk factors, except smoking, increased with age. Average SCORE index was 1.87 in all study population, while dyslipidemic subjects had higher SCORE compared to control group (1.95 vs 1.20, p < 0.001). CONCLUSIONS: Almost two thirds of dyslipidemic middle-aged Lithuanian adults without overt cardiovascular disease had three or more other CVD risk factors, which synergistically increase absolute risk of CVD. The average 10-year risk of CVD death in patients with dyslipidemia was 1.95%. The importance of managing dyslipidemia as well as other risk factors in order to reduce burden of cardiovascular disease in Lithuania is evident.

Cardiovascular risk profile of patients with atherogenic dyslipidemia in middle age Lithuanian population.

BACKGROUND: Atherogenic dyslipidemia (AD) is a blood serum lipid profile abnormality characterized by elevation of triglycerides and reduced levels of high density lipoprotein cholesterol (HDL-C). It is associated with residual cardiovascular risk. This study evaluated and compared the risk profiles of patients with hypertriglyceridemia, low-HDL-C levels or AD, in order to understand, which lipid profile is associated with greater risk. METHODS: During the period of 2009-2016 a population of 92,373 Lithuanian adults (men 40-54 years old and women 50-64 years old) without overt cardiovascular disease were analyzed. Data of 25,746 patients (68.6% women and 31.4% men) with hypertriglyceridemia and/or low HDL-C low levels were collected and used for further statistical analysis. RESULTS: Participants with AD tend to have more unfavorable risk profile than participants with hypertriglyceridemia or low-HDL-C. AD tends to cluster with other atherogenic risk factors, such as arterial hypertension [odds ratio (OR) 1.96, 95% confidence intervals (CI) 1.87-2.01], smoking [OR 1.20, 95% CI 1.14-1.27], diabetes mellitus [OR 2.74, 95% CI 2.58-2.90], obesity [OR 2.92, 95% CI 2.78-3.10], metabolic syndrome [OR 22.27, 95% CI 20.69-23.97], unbalanced diet [OR 1,59, 95% CI 1.51-1.68], low physical activity [OR 1.80, 95% CI 1.71-1,89], CHD history in first degree relatives [OR 1.18, 95% CI 1.12-1.25] and total number of risk factors [OR 1.47, 95% CI 1.38-1.57]. CONCLUSION: AD is associated with more unfavorable cardiovascular risk profile than hypertriglyceridemia or low-HDL cholesterol levels. Once identified AD should require additional medical attention since it is an important factor of residual cardiovascular risk.

Impact of renal sympathetic denervation on cardiac sympathetic nerve activity evaluated by cardiac MIBG imaging.

AIMS: The objective of the present study was to investigate an effect of renal artery sympathetic denervation (RASD) on patients with resistant hypertension and RASD effect on cardiac sympathetic nerve activity. It is known that an abnormally activated sympathetic tone is associated with progression of heart failure (HF). METHODS AND RESULTS: We investigated 16 patients with resistant arterial hypertension (mean age 54.88±7.89 years, mean 24-hr ambulatory blood pressure [BP] systolic 161.07±20.12 mmHg, diastolic 97.6±16.25 mmHg, using 6.44±0.96 antihypertensive drugs), who underwent bilateral RASD. Echocardiography, 24-hr ambulatory BP and 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy were performed before and six months after RASD. There were no significant changes in 24-hr ambulatory systolic and diastolic BP before RASD and six months after it: systolic BP before RASD was 161.07±20.12 mmHg and 144.93±17.27 mmHg after (p=0.050); diastolic BP before RASD was 97.6±16.25 mmHg and 89.87±12.33 mmHg after (p=0.182). We observed a significant change in cardiac sympathetic nerve activity assessed by 123I-MIBG scintigraphy, as an increase of late heart-to-mediastinum (H/M) ratio, varying from 2.21±0.47 to 2.35±0.52 m/s (p=0.02). CONCLUSIONS: Selective RASD significantly reduces cardiac sympathetic overdrive assessed by 123I-MIBG scintigraphy. Presumably, this positively affects HF progression in patients with resistant arterial hypertension.