Lipid-Lowering Treatment Gaps in Patients after Acute Myocardial Infarction: Using Global Database TriNetX.

Background and Objectives: Patients with previous acute myocardial infarction are at significantly higher risk of recurrent events. Early and intensive lipid-lowering therapy targeting low-density lipoprotein cholesterol is a key strategy for reducing cardiovascular risk in post-acute myocardial infarction patients worldwide. This study aimed to assess patients' real-life lipid-lowering treatment gaps after acute myocardial infarction using a global network, TriNetX, of anonymous, real-time patient data. The uniqueness of the study was the use of the novel, evolving, and constantly improving TriNetX platform and the evaluation of its feasibility for clinical research. Materials and Methods: A retrospective study was conducted on global repository patients in 2020, diagnosed with acute myocardial infarction, with a three-year follow-up. Results: After acute myocardial infarction, the prescribing rate of lipid-lowering medication (statins, ezetimibe and PCSK9I) was insufficient to reach target LDL-C values. The mean LDL-C level decreased from 2.7 mmol/L (103 mg/dL) as measured on the day of AMI to 1.97 mmol/L (76 mg/dL) between 31D and 3M. During the second and third years, the mean LDL-C value was stable (around 2.0 mmol/L (78 mg/dL)). LDL-C goals were not sufficiently reached, as only 7-12% of patients were reported to have LDL-C values < 55 mg/dL (1.4 mmol/L) and 13-20% of patients were reported to have LDL-C values < 70 mg/dL (1.8 mmol/L) during the follow-up periods. This means that a substantial number of patients remain at a very high risk for CV complications and mortality. Most cardiovascular complications happen within three months after acute myocardial infarction. Conclusions: Gaps remain between the recommendations for managing LDL-C in guidelines and what occurs in real life. The TriNetX platform is an innovative platform with significant potential and should be further developed for clinical research, as it enables the use of valuable interinstitutional data.

The Hypertension Excellence Centre programme of the European Society of Hypertension - current status, activities and reshaping for the future.

PURPOSE: To describe the history of the Excellence Centre (EC) programme of the European Society of Hypertension (ESH) since the beginning in 2006, its achievements, and its future developments. MATERIALS AND METHODS: We list the number of ECs per country, the research projects performed so far, and the organisational steps needed to reshape the EC programme for the future. RESULTS: In August 2023, the ESH EC programme includes 118 registered ECs in 21 European and 7 non-European countries. Updates about the formal steps for application, re-application, transfer of EC and retirement of EC heads are given. CONCLUSIONS: The EC programme of the ESH has been a success from the beginning. Further refinements will make it fit for the next decades.

The Impact of Marathons on the Recovery of Heart Rate and Blood Pressure in Non-Professional Male Marathoners' (≥45 Years).

Background and Objectives: Physical activity has a positive impact on health, and the participation in exercise and sports, including marathons, has increased in popularity. This kind of sport requires extreme endurance, which can cause different health problems and even lead to death. Participants without sufficient preparation and, in particular, men 45 years of age and older belong to a high risk group. The aim of this study was to determine the impact of marathons and cofactors associated with marathons on the recovery of heart rate (HR) and blood pressure (BP) of non-professional ≥ 45 years old male marathoners. Materials andMethods: A total of 136 ≥ 45 year old, non-professional (amateur marathoner), male participants were recruited. Data collection involved a questionnaire, body composition measures, and BP and HR results before and after finishing the marathon. Descriptive data, t-test, Mann-Whitney or χ2 test, and Pearson's correlation were applied. Results: Participants (skiing n = 81, cycling n = 29, running n = 26; mean age 51.7 ± 7.1 years old) had previously attended a median of 35 (IQR 17.5-66) marathons and travelled 2111.5 (IQR 920-4565) km. Recovery of HR and BP after finishing and recovery time was insufficient and not associated with marathon preparation. Running was the most burdensome for HR, and cycling was most taxing for BP. Chronic diseases did not influence participation in the marathon. Conclusions: The preparation for the marathon was mainly sufficient, but recovery after the marathon was worrisome. Marathons are demanding for ≥45 year old males and may be too strenuous an activity that has deleterious effects on health.

Hypertension and Reproduction.

PURPOSE OF REVIEW: Many aspects of reproduction have been associated with increased blood pressure and impaired glucose metabolism that reveals a subsequent increased risk of cardiovascular disease. The aim of this review is to assess reproductive life factors associated with an increased risk of hypertension and cardiovascular disease, e.g., early life programming, sexual, and reproductive health in men and women. RECENT FINDINGS: Impaired fetal growth, with low birth weight adjusted for gestational age, has been found associated with hypertension in adulthood. Erectile dysfunction, currently considered an early diagnostic marker of cardiovascular disease preceding the manifestation of coronary artery disease by several years, frequently coexisting with hypertension, could also be exacerbated by some antihypertensive drugs. Male hypogonadism or subfertility are associated with increased cardiovascular risk. Hypertensive disorders in pregnancy including preeclampsia represent a major cause of maternal, fetal and neonatal morbidity, and mortality. The risk of developing preeclampsia can be substantially reduced in women at its high or moderate risk with a low dose of acetylsalicylic acid initiated from 12 weeks of gestation. An increased risk of hypertension in women following invasive-assisted reproductive technologies has been newly observed. Blood pressure elevation has been noticed following contraceptive pill use, around the menopause and in postmenopausal age. Furthermore, drug treatment of hypertension has to be considered as a factor with a potential impact on reproduction (e.g., due to teratogenic drug effects). In summary, a deeper understanding of reproductive life effects on hypertension and metabolic abnormalities may improve prediction of future cardiovascular disease.

Digital Health in Cardiology: The Estonian Perspective.

BACKGROUND: Digital health is rapidly entering clinical practice in cardiology. Estonia is one of the leading nations in implementing digital nationwide solutions. Recently, the European Society of Cardiology organized the 1st Summit on Digital Health in Tallinn, which provided the opportunity to discuss various aspects concerning the digitalization of cardiology. SUMMARY: The current review focuses on the advancements of Estonian digital health and digital cardiology as well as possible barriers and solutions for implementing digital innovations in cardiology. Key Messages: The authors have included aspects from the recent summit, personal communications, and literature reviews to express the current state and future possibilities of digital health in -cardiology from the Estonian perspective.

Rapid socio-economic changes, psychosocial factors and prevalence of hypertension among men and women aged 55 years at baseline in Estonia: a 13-year follow-up study.

BACKGROUND: Hypertension is an important public health problem which causes premature morbidity and mortality. Cardiovascular diseases are responsible for about 55% of deaths in Estonia. THE PURPOSE OF THE STUDY: was to assess, through a follow-up period, the prevalence of hypertension and to observe which risk factors of cardiovascular disease impact the occurrence of the disease. The second aim of the study was to evaluate the role of psychosocial factors and personality traits among individuals with a diagnosis of hypertension. MATERIALS AND METHODS: The 330 subjects from Estonia, aged 55 years at baseline, from among whom 219 participated at follow-up. A cross-sectional study based on a self-reported questionnaire was conducted. RESULTS: Over 13 years, the prevalence of hypertension increased from 4% to 53%. Obese (body mass index ≥30 kg/m2) individuals were four times more likely to belong to the hypertension group (p < .01). Among individuals with hypertension the depressed mood score was ≥4 points (max. 9 points) in 54.3% of participants. Depressed mood was linked with experiencing negative stressful life events (B = 0.047, 95% CI 0.016; 0.079; p < .01). Mastery had a protective impact on depressed mood. The self-rated quality of life score was lower among subjects with hypertension than among those who were not diagnosed with hypertension (p < .05). CONCLUSIONS: According to the 13-year follow-up study, rapid socio-economic changes in Estonia have affected psychosocial health factors among 55-year-old individuals with a diagnosis of hypertension. There is a significant relationship between obesity and the development of hypertension.

Non-invasive hemodynamic monitoring as a guide to drug treatment of uncontrolled hypertensive patients: effects on home blood pressure in the BEAUTY study.

BACKGROUND: In the BEAUTY study we investigated whether utilizing non-invasive monitoring of hemodynamic parameters combined with a drug selection algorithm (integrated hemodynamic management-IHM) compared to conventional drug selection may improve home BP in patients with uncontrolled hypertension. METHODS: Uncontrolled (office systolic blood pressure (SBP) > 140 mmHg and ambulatory daytime SBP >135 mmHg while taking ≥2 antihypertensive drugs) essential hypertensive patients were referred to 5 European Hypertension Excellence Centers and, if eligible, were randomized into IHM-guided vs conventional treatment adjustment. Home blood pressure (BP) was taken with 2 repeated readings at 1-2 min intervals in the morning and in the evening (before drug intake and eating) during the week preceding the visit at the outpatient clinic after 5 min rest using a validated semi-automatic oscillometric arm cuff device and with a correct cuff bladder placement. Home blood pressure was measured in a sub-group of patients (n = 84) not significantly different from the other patients. RESULTS: Home SBP changed from 152.1+/-15.8 and 149.8+/-11.8 mmHg to 131.0 +/-11.1 and 139.6+/-12.8 mmHg in IHM group (n = 46) and Control group (n = 38), respectively, showing significantly greater reduction in IHM than in Control group (d= -10.9 mmHg, 95% CI -17.77, -4.02), p = 0.002. The reduction remained significant after multiple adjustments, particularly for baseline home SBP, recruiting center, age, sex and BMI (SBPIHM-Control= -9,63 mmHg, 95% CI -14.28, -5.11) mmHg, p < 0.0001). CONCLUSION: Drug selection algorithm based on non-invasive hemodynamic monitoring induced larger reduction in home BP compared to conventional drug selection in uncontrolled hypertensive patients referred to European Hypertension Excellence Centers. Although the main BEAUTY study was negative, these home BP measurements taken by patients themselves may suggest that the integrated hemodynamic monitoring is useful in patients with uncontrolled hypertension. This finding might depend on specific features of home BP measurements which could make it recommended BP measurement method for drug trials.

Preclinical evaluation of a semi-automated and rapid commercial electrophoresis assay for von Willebrand factor multimers.

BACKGROUND: The von Willebrand factor (VWF) multimer test is required to correctly subtype qualitative type 2 von Willebrand disease (VWD). The current VWF multimer assays are difficult, nonstandardized, and time-consuming. The purpose of this study was to evaluate the clinical utility of the commercial VWF multimer kit by Sebia (Lisses, France), an electrophoresis technique yielding same-day results. METHODS: Ten healthy volunteer plasma samples, in-house reference plasma (IRP) and commercial normal plasma (CNP) samples, 10 plasma samples from patients with a known VWD type, 1 hemophilia A plasma sample, and 7 external quality assurance (EQA) samples were analyzed using the commercial VWF multimer kit. Additional coagulation testing included measurements of VWF antigen (VWF:Ag), VWF activity (VWF:Ac), and FVIII activity (FVIII:C). RESULTS: The CNP results revealed a relative loss of the highest molecular weight multimers; therefore, IRP was preferred as the reference sample. The interpretations of 10 patients with a known VWD type could be successfully reproduced and agreed with previous VWF multimer results. In all EQA surveys, the multimer results and final VWD diagnosis agreed with expert opinion. CONCLUSIONS: The VWF multimer assay by Sebia is easy to perform and can be successfully implemented in any clinical laboratory for second-stage evaluation of VWD. The resolution power of multimer distribution is adequate to correctly classify VWD types 1, 2A, 2B, and 3.

Prevalence of cardiovascular disease risk factors in Tallinn, Estonia.

BACKGROUND AND OBJECTIVE: Cardiovascular diseases are still a major public health concern in Estonia despite the decline in the mortality rate during the past decade. For better preventive strategies we aimed to investigate the prevalence of cardiovascular disease risk factors and their relations with age, gender and ethnicity. MATERIALS AND METHODS: The cross-sectional study was carried out in Tallinn, Estonia. Two hundred individuals from each of the sex and 10-year age group (range 20-65 years of age) were randomly selected and invited to participate. Final study sample consisted of 511 men and 600 women (mean age of 46 years). Physiological measurements were taken and blood samples were drawn for standard measurements of the following markers: total cholesterol, high- and low-density lipoprotein cholesterol, apolipoproteins, triglycerides, glucose and inflammatory markers. RESULTS: Overall, 31% of the study subjects had high blood pressure, 23% had metabolic syndrome, and 55% were overweight/obese. The prevalence of all risk factors increased with age amongst both genders. The proportion of individuals having increased cholesterol, apolipoprotein B-100, and homocysteine levels was very high amongst both genders (60-80%). More Russians and other ethnic minorities compared to ethnic Estonians had calculated 10-year CHD risk≥10%. CONCLUSIONS: The study established a high prevalence of cardiovascular disease risk factors in Estonian adults (20-65 years of age). Younger portion of the population and some extent ethnic considerations should be taken into account when designing future studies, health prevention activities and interventions.

Current practice in identifying and treating cardiovascular risk, with a focus on residual risk associated with atherogenic dyslipidaemia.

A panel of European experts on lipids and cardiovascular disease discussed clinical approaches to managing cardiovascular risk in clinical practice, including residual cardiovascular risk associated with lipid abnormalities, such as atherogenic dyslipidaemia (AD). A simplified definition of AD was proposed to enhance understanding of this condition, its prevalence, and its impact on cardiovascular risk. Atherogenic dyslipidaemia can be defined by high fasting triglyceride levels (≥2.3 mmol/L) and low high-density lipoprotein cholesterol (HDL-c) levels (≤1.0 and ≤1.3 mmol/L in men and women, respectively) in statin-treated patients at high cardiovascular risk. The use of a single marker for the diagnosis and treatment of AD, such as non-HDL-c, was advocated. Interventions including lifestyle optimization and low-density lipoprotein (LDL)-lowering therapy with statins (±ezetimibe) are implemented by all experts. Treatment of residual AD can be performed with the addition of fenofibrate, since it can improve the complete lipoprotein profile and reduce the risk of cardiovascular events in patients with AD. Specific clinical scenarios in which fenofibrate may be prescribed are discussed, and include patients with very high triglycerides (≥5.6 mmol/L), patients who are intolerant or resistant to statins, and patients with AD and at high cardiovascular risk. The fenofibrate-statin combination was considered by the experts to benefit from a favourable benefit-risk profile. Cardiovascular experts adopt a multifaceted approach to the prevention of atherosclerotic cardiovascular disease, with lifestyle optimization, LDL-lowering therapy, and treatment of AD with fenofibrate routinely used to help reduce a patient's overall cardiovascular risk.

The initiation of free radical peroxidation of low-density lipoproteins by glucose and its metabolite methylglyoxal: a common molecular mechanism of vascular wall injure in atherosclerosis and diabetes.

It was found that glucose in the range of concentrations 12.5-100 mM stimulated Cu(2+)-mediated free radical peroxidation of low-density lipoproteins (LDL) from human blood plasma. Considering the kinetic parameters of LDL peroxidation we proposed that intensification of this process may be caused by formation of free radical intermediates of glucose auto-oxidation. Addition of SOD to the medium inhibited LDL oxidation, indicating the formation of superoxide anion-radicals under autoxidation of glucose. Similarly, SOD inhibited free radical peroxidation of liposomes from egg lecithin in the presence of glucose that confirms the generation of superoxide radicals under co-oxidation of unsaturated lipids and glucose. Normalization of glucose level in the blood of patients with type 2 diabetes mellitus during therapy was accompanied by a significant decrease in LDL oxidation in vivo (the decrease in primary and secondary lipoperoxidation products). The formation of superoxide anion-radicals was observed during interaction of aminoacid L-lysine with a product of glucose oxidative metabolism-methylglyoxal, but not with a product of lipoperoxidation malonyldialdehyde. In accordance with the foregoing the administration of sugar-lowering drug metformin, which binds and utilizes methylglyoxal, caused a stronger inhibition of LDL peroxidation in the blood of patients with diabetes mellitus, probably due to decrease in methylglyoxal-dependent generation of superoxide anion-radicals. Based on the results we set out the hypothesis about autocatalytic mechanism of free radical reactions involving natural dicarbonyls and suppose the common molecular mechanism of vascular wall injury in atherosclerosis and diabetes.

Prevalence and determinants of hypertension in Estonian adults.

BACKGROUND: Although Eastern Europe, including Estonia, has one of the highest morbidity and mortality rates associated with hypertension, there is little information in the literature concerning the biochemical risk factor profile or its association with hypertension in Estonia. This study examined the cross-sectional gender-stratified association between biochemical risk markers and hypertension in a population-based sample of adults in Estonia. METHODS: The study was carried out in Tallinn, Estonia and consisted of 511 men and 600 women with a mean age of 46 years. Physiological measurements were taken and blood samples drawn to measure the following markers: cholesterol, high- and low-density lipoprotein cholesterol, apolipoproteins A-1 and B, lipoprotein(a), triglycerides, glucose, fibrinogen, high-sensitivity C-reactive protein and homocysteine. RESULTS: Overall, 36% of participants had hypertension, with approximately 80% being aware of their condition. A total of 40% of participants reported taking antihypertensive medication. Multivariate binary logistic regression analysis showed that a decrease in high-density lipoprotein cholesterol and increases in age, body mass index, apolipoprotein B, triglyceride and homocysteine levels were associated with an increased probability of hypertension. CONCLUSIONS: Elevations in biochemical markers and cardiovascular risk factors are associated with hypertension. Increasing body mass index, triglyceride, apolipoprotein B and homocysteine levels with decreasing high-density lipoprotein cholesterol level should be investigated and monitored in Estonian adults.

Impact of smoking: all-cause and cardiovascular mortality in a cohort of 55-year-old Swedes and Estonians.

AIM: In the 1990s, several studies noted a large gap in life expectancy between Western and Eastern European countries. It was speculated that this could be explained by environmental pollution, socioeconomic factors, lifestyle and psychosocial stress. A weakness in addressing the issue has been the lack of prospective studies with mortality as end point. METHODS: We used the national population registries (between 1996 and 1998) to screen a cohort of 269 55-year-old subjects in Sweden and Estonia. We assessed conventional risk factors, lifestyle and socio-economic factors. A 13-year follow-up regarding all-cause and cardiovascular mortality was done. RESULTS: Smoking and, to a lesser extent, plasma levels of interleukin-6 were significant predictors for CVD and non-CVD mortality in men, but none of the other conventional risk factors reached statistical significance. During the follow-up period, 22 of the 52 male smokers died compared to 8 of the 85 male non-smokers (p<0.01). Ten of the smokers died of CVD compared to three of the non-smokers (p<0.002). In total, only two women died. CONCLUSIONS: These data emphasize that smoking prevention is extremely important in preventing premature death. Although smoking prevalence is diminishing, it is still the most important risk factor to treat.

Prevalence of dyslipidemia in statin-treated patients in the Baltic states (Estonia, Latvia, and Lithuania): results of the Dyslipidemia International Study (DYSIS).

BACKGROUND AND OBJECTIVE: The Baltic nations (Estonia, Latvia, and Lithuania) are profoundly affected by cardiovascular disease (CVD). Studies have indicated that patients may experience persistent dyslipidemia despite chronic statin treatment. Therefore, the aim of this study was to analyze the risk factors for dyslipidemia despite statin-treatment in a large dataset from the Baltic nations. MATERIAL AND METHODS: Patients in primary care centers across the Baltic nations were enrolled into the cross-sectional, observational Dyslipidemia International Study (DYSIS). Patients were ≥ 45 years old and had been treated with statins for at least three months. Patient characteristics and lipid measurements were used to determine variables contributing to dyslipidemia (abnormal low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], or total triglyceride [TG] values). RESULTS: We enrolled 1797 patients with a mean age of 66.1 years and 59.1% being female. Overall 63.4% had cardiovascular disease, 30.1% were diabetic and 77.8% at high risk for cardiovascular complications. LDL-C was not at target level for 80.7%; low HDL-C levels were observed for 26.0%, and elevated TG levels were found in 35.0% of all patients. Multivariate analyses indicated that a BMI ≥ 30 kg/m(2) (OR, 2.12; 95% CI, 1.45-3.08) and hypertension (OR, 2.43; 95% CI, 1.1 6-5.10) were strongly associated with dyslipidemia (involving all three lipids) during statin therapy while age ≥ 70 years (OR, 0.63; 95% CI, 0.42-0.94) and female gender (OR, 0.48; 95% CI, 0.33-0.68) conferred reduced risk. CONCLUSIONS: Our findings indicate many statin-treated patients in Estonia, Latvia, and Lithuania did not meet target lipid levels and had a very high risk of CVD. Combating other well-known CVD risk factors such as obesity and hypertension is vital to reduce the exceptionally high risk for CVD mortality seen in the Baltic nations.

2024 Recommendations on the Optimal Use of Lipid-Lowering Therapy in Established Atherosclerotic Cardiovascular Disease and Following Acute Coronary Syndromes: A Position Paper of the International Lipid Expert Panel (ILEP).

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease's burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), "lower is better for longer", and recent data have strongly emphasised the need for also "the earlier the better". In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of "extremely high-risk" individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy's effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries.

New photoplethysmographic signal analysis algorithm for arterial stiffness estimation.

The ability to identify premature arterial stiffening is of considerable value in the prevention of cardiovascular diseases. The "ageing index" (AGI), which is calculated from the second derivative photoplethysmographic (SDPPG) waveform, has been used as one method for arterial stiffness estimation and the evaluation of cardiovascular ageing. In this study, the new SDPPG analysis algorithm is proposed with optimal filtering and signal normalization in time. The filter parameters were optimized in order to achieve the minimal standard deviation of AGI, which gives more effective differentiation between the levels of arterial stiffness. As a result, the optimal low-pass filter edge frequency of 6 Hz and transitionband of 1 Hz were found, which facilitates AGI calculation with a standard deviation of 0.06. The study was carried out on 21 healthy subjects and 20 diabetes patients. The linear relationship (r = 0.91) between each subject's age and AGI was found, and a linear model with regression line was constructed. For diabetes patients, the mean AGI value difference from the proposed model y AGI was found to be 0.359. The difference was found between healthy and diabetes patients groups with significance level of P < 0.0005.

Blood pressure control and cardiovascular risk profile in hypertensive patients from central and eastern European countries: results of the BP-CARE study.

AIMS: Limited information is available on office and ambulatory blood pressure (BP) control as well as on cardiovascular (CV) risk profile in treated hypertensive patients living in central and eastern European countries. METHODS AND RESULTS: In 2008, a survey on 7860 treated hypertensive patients followed by non-specialist or specialist physicians was carried out in nine central and eastern European countries (Albania, Belarus, Bosnia, Czech Republic, Latvia, Romania, Serbia, Slovakia, and Ukraine). Cardiovascular risk assessment was based on personal history, clinic BP values, as well as target organ damage evaluation. Patients had a mean (±SD) age of 60.1 ± 11 years, and the majority of them (83.5%) were followed by specialists. Average clinic BP was 149.3 ± 17/88.8 ± 11 mmHg. About 70% of patients displayed a very high-risk profile. Electrocardiogram was performed in 99% of patients, echocardiography in 65%, carotid ultrasound in 24%, fundoscopy in 68%, and search for microalbuminuria in 10%. Ambulatory BP monitoring was performed in about one-fifth of the recruited patients. Despite the widespread use of combination treatment (87% of the patients), office BP control (<140/90 mmHg) was achieved in 27.1% only, the corresponding control rate for ambulatory BP (<130/80 mmHg) being 35.7%. Blood pressure control was (i) variable among different countries, (ii) worse for systolic than for diastolic BP, (iii) slightly better in patients followed by specialists than by non-specialists, (iv) unrelated to patients' age, and (v) more unsatisfactory in high-risk hypertensives and in patients with coronary heart disease, stroke, or renal failure. CONCLUSION: These data provide evidence that in central and eastern European countries office and ambulatory BP control are unsatisfactory, particularly in patients at very high CV risk, and not differ from that seen in Western Europe. They also show that assessment of subclinical organ damage is quite common, except for microalbuminuria, and that combination drug treatment is frequently used.

Effectiveness and feasibility of cardiovascular disease personalized prevention on high polygenic risk score subjects: a randomized controlled pilot study.

Aims: The aim of this study was to evaluate the effect of the intervention by proactively sharing a patient's high polygenic risk score (PRS) for coronary artery disease (CAD). Outcomes included: (i) reduction in cardiovascular disease (CVD) risk factors over 12 months; (ii) difference in purchased prescriptions of lipid-lowering and anti-hypertensive drugs between intervention group and control group subjects; and (iii) opinion of the participating physicians and subjects on PRS usefulness. Methods and results: This randomized controlled trial was conducted among middle-aged subjects with a top 20% CAD PRS in a family medicine setting. Participants were selected from 26 953 Estonian Biobank cohort participants. Subjects were informed and counselled about their PRS score and CAD risk using the visual tool at baseline (Visit I), counselling session (Visit II), and on the final Visit III at 12 months. The primary endpoint was not significantly different. However, the intervention group participants had a significantly higher probability of initiating statin treatment compared with the controls. Their levels of LDL-cholesterol (LDL-C) were significantly decreased compared with baseline on Visit III and significantly lower than in the control group. The vast majority of participating family physicians believe that finding out about genetic risks will affect the subject's lifestyle and medication compliance. Conclusion: Most of our outcome measures were in favour of this intervention. Participants achieved larger changes in cholesterol and blood pressure values. The vast majority (98.4%) of family physicians are interested in continuing to use genetic risk assessment in practice.

Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans.

Mutations in WNK1 and WNK4 cause familial hypertension, the Gordon syndrome. WNK1 and WNK4 conserved noncoding regions were targeted to polymorphism screening using DHPLC and DGGE. The scan identified an undescribed polymorphic AluYb8 insertion in WNK1 intron 10. Screening in primates revealed that this Alu-insertion has probably occurred in human lineage. Genotyping in 18 populations from Europe, Asia, and Africa (n = 854) indicated an expansion of the WNK1 AluYb8 bearing chromosomes out of Africa. The allele frequency in Sub-Saharan Africa was ~3.3 times lower than in other populations (4.8 vs. 15.8%; P = 9.7 × 10(-9) ). Meta-analysis across three European sample sets (n = 3,494; HYPEST, Estonians; BRIGHT, the British; CADCZ, Czech) detected significant association of the WNK1 AluYb8 insertion with blood pressure (BP; systolic BP, P = 4.03 × 10(-3) , effect 1.12; diastolic BP, P = 1.21 × 10(-2) , effect 0.67). Gender-stratified analysis revealed that this effect might be female-specific (n = 2,088; SBP, P = 1.99 × 10(-3) , effect 1.59; DBP P = 3.64 × 10(-4) , effect 1.23; resistant to Bonferroni correction), whereas no statistical support was identified for the association with male BP (n = 1,406). In leucocytes, the expressional proportions of the full-length WNK1 transcript and the splice-form skipping exon 11 were significantly shifted in AluYb8 carriers compared to noncarriers. The WNK1 AluYb8 insertion might affect human BP via altering the profile of alternatively spliced transcripts.

Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations.

Hypertension is a complex disease that affects a large proportion of adult population. Although approximately half of the inter-individual variance in blood pressure (BP) level is heritable, identification of genes responsible for its regulation has remained challenging. Genome-wide association study (GWAS) is a novel approach to search for genetic variants contributing to complex diseases. We conducted GWAS for three BP traits [systolic and diastolic blood pressure (SBP and DBP); hypertension (HYP)] in the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) S3 cohort (n = 1644) recruited from general population in Southern Germany. GWAS with 395,912 single nucleotide polymorphisms (SNPs) identified an association between BP traits and a common variant rs11646213 (T/A) upstream of the CDH13 gene at 16q23.3. The initial associations with HYP and DBP were confirmed in two other European population-based cohorts: KORA S4 (Germans) and HYPEST (Estonians). The associations between rs11646213 and three BP traits were replicated in combined analyses (dominant model: DBP, P = 5.55 x 10(-5), effect -1.40 mmHg; SBP, P = 0.007, effect -1.56 mmHg; HYP, P = 5.30 x 10(-8), OR = 0.67). Carriers of the minor allele A had a decreased risk of hypertension. A non-significant trend for association was also detected with severe family based hypertension in the BRIGHT sample (British). The novel susceptibility locus, CDH13, encodes for an adhesion glycoprotein T-cadherin, a regulator of vascular wall remodeling and angiogenesis. Its function is compatible with the BP biology and may improve the understanding of the pathogenesis of hypertension.