Pharmacogenetics of Cardiovascular Disease: Genetic Variation and Statin Intolerance

Statins are very effective for lowering low-density lipoprotein cholesterol for primary and secondary cardiovascular disease prevention. While statins are usually well tolerated, individual response to statin therapy varies and intolerance, predominantly muscle symptoms, may appear in a significant proportion of patients. Besides clinical factors, variation in genes coding for proteins with drug transporting, immune or enzymatic function have been implicated in the pathogenesis of statin intolerance. In this review, we will characterise the candidate gene variants for development of statin intolerance, describe their population distribution and summarise current knowledge on their biological plausibility. Clinical relevance and current guidelines/recommendations will be also discussed

Quarterly vs. yearly clinical follow-up of remotely monitored recipients of prophylactic implantable cardioverter-defibrillators: results of the REFORM trial

Aims The rapidly increasing number of patients with implantable cardioverter-defibrillators (ICD) places a large burden on follow-up providers. This study investigated the possibility of longer in-office follow-up intervals in primary prevention ICD patients under remote monitoring with automatic daily data transmissions from the implant memory. Methods and results Conducted in 155 ICD recipients with MADIT II indications, the study compared the burden of scheduled and unscheduled ICD follow-up visits, quality of life (SF-36), and clinical outcomes in patients randomized to either 3- or 12-month follow-up intervals in the period between 3 and 27 months after implantation. Remote monitoring (Biotronik Home Monitoring) was used equally in all patients. In contrast to previous clinical studies, no calendar-based remote data checks were performed between scheduled in-office visits. Compared with the 3-month follow-up interval, the 12-month interval resulted in a minor increase in the number of unscheduled follow-ups (0.64 vs. 0.27 per patient-year; P = 0.03) and in a major reduction in the total number of in-office ICD follow-ups (1.60 vs. 3.85 per patient-year; P < 0.001). No significant difference was found in mortality, hospitalization rate, or hospitalization length during the 2-year observation period, but more patients were lost to follow-up in the 12-month group (10 vs. 3; P = 0.04). The SF-36 scores favoured the 12-month intervals in the domains ‘social functioning' and ‘mental health'. Conclusion In prophylactic ICD recipients under automatic daily remote monitoring, the extension of the 3-month in-office follow-up interval to 12 months appeared to safely reduce the ICD follow-up burden during 27 months after implantation. ClinicalTrials.gov Identifier NCT00401466 (http://www.clinicaltrials.gov/ct2/show/NCT00401466

Catheter-based renal denervation versus intensified medical treatment in patients with resistant hypertension: Rationale and design of a multicenter randomized study—PRAGUE-15

AbstractCatheter-based renal denervation (RDN) was considered as a promising method for treatment of resistant hypertension and was increasingly being used worldwide. However, there are equivocal results from only two randomized trials studying the effect of such intervention. Thus, additional data from properly designed long-term comparative trials are needed. The PRAGUE-15 trial is designed as an open, prospective, randomized multicenter trial comparing RDN versus intensified medical treatment in patients with resistant hypertension. Patients randomized to the medical treatment group will receive spironolactone in the absence of contraindications. The primary endpoint will be changes in systolic and diastolic pressure during ambulatory blood pressure monitoring (ABPM) from baseline to 6 months. Herein, we describe the trial design and methodology. The strengths of the trial include ABPM (as the objective endpoint), independent outcomes assessment, and therapeutic use of spironolactone

CCL5/RANTES Gene Polymorphisms in Slavonic Patients with Myocardial Infarction

Coronary artery inflammation is a critical process in the pathogenesis of myocardial infarction (MI). The chemokine CCL5/RANTES (regulated upon activation, normal T cells expressed and secreted) is expressed in advanced atherosclerotic lesions. Functional polymorphisms of the RANTES gene can, therefore, be involved in the pathogenesis of coronary artery disease. We examined the association of polymorphisms in the RANTES gene with myocardial infarction in Slavonic populations of Czech and Russian origin. A total of 467 post-MI patients and 337 control subjects were genotyped for RANTES promoter G-403A (rs2107538) and intron 1.1 T/C (rs2280789) variants by PCR-SSP. Both RANTES genotypes and allele frequencies did not differ between case and control groups. Haplotype-based analysis also failed to reveal an association between MI and investigated markers. Strong linkage disequilibrium was detected between particular RANTES alleles. The data do not support an association between RANTES G-403A polymorphism and MI, as reported previously

The Role of Renal Vascular Reactivity in the Development of Renal Dysfunction in Compensated and Decompensated Congestive Heart Failure

Background/Aims: Reduction of renal blood flow (RBF) is commonly thought to be a causative factor of renal dysfunction in congestive heart failure (CHF), but the exact mechanism of the renal hypoperfusion is not clear. Apart from the activation of neurohormonal systems controlling intrarenal vascular tone, the cause might be altered reactivity of the renal vasculature to endogenous vasoactive agents. Methods: To evaluate the role of this mechanism, we assessed by an ultrasonic transient-time flow probe maximum RBF responses to renal artery infusion of angiotensin II (ANG II), norepinephrine (NE) and acetylcholine (Ach) in healthy male rats and animals with compensated and decompensated CHF. CHF was induced by volume overload achieved by the creation of the aorto-caval fistula (ACF) in Hannover Sprague-Dawley rats. Results: Maximum responses in RBF to ANG II were similar in rats studied five weeks (compensated phase) and 20 weeks (decompensated phase) after ACF creation when compared to sham-operated rats. On the other hand, NE elicited larger maximum decreases in RBF in rats with CHF (five and 20 weeks post-ACF) than in sham-operated controls. We observed greater maximum vasodilatory responses to Ach only in rats with a compensated stage of CHF (five weeks post-ACF). Conclusion: Greater renal vasoconstrictor responsiveness to ANG II or reduced renal vasodilatation in response to Ach do not play a decisive role in the development of renal dysfunction in ACF rats with compensated and decompensated CHF. On the other hand, exaggerated renal vascular responsiveness to NE may be here a contributing causative factor, active in either CHF phase

European Society of Cardiology: Cardiovascular Disease Statistics 2019

Aims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets. Methods and results In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index ≥30 kg/m2) and diabetes has increased two- to three-fold during the last 30 years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20 years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5–23.1%] vs. 15.7% (IQR 14.5–21.1%)}, diabetes [7.7% (IQR 7.1–10.1%) vs. 5.6% (IQR 4.8–7.0%)], and among males smoking [43.8% (IQR 37.4–48.0%) vs. 26.0% (IQR 20.9–31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0–10.8) vs. 16.7% (IQR 13.9–19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655–8115)] compared with high-income [2235 (IQR 1896–3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures. Conclusion A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest

Let It Beat: How Lifestyle and Psychosocial Factors Affect the Risk of Sudden Cardiac Death&mdash;A 10-Year Follow-Up Study

(1) Background: The aim of this study was to evaluate the lifestyle and occurrence of psychosocial factors in patients with a high risk of sudden cardiac death (SCD) and to explore their effect on the occurrence of the adequate therapy of an Implantable Cardioverter Defibrillator (ICD). (2) Methods: In this retro-prospective single-centre study, a group of patients aged 18&ndash;65 years old, who underwent the first ICD implantation for primary (PP) or secondary (SP) prevention between 2010&ndash;2014, was studied. The control group consisted of pair-matched (age &plusmn; 5 years, gender) respondents without a high risk of SCD. Information was obtained using a self-reported questionnaire and hospital electronic health records. The adequacy of ICD therapy was evaluated regularly until 31 January 2020. Multivariate logistic regression models were employed to assess the risk of SCD. (3) Results: A family history of SCD, coronary artery disease, diabetes mellitus and depression significantly aggravated the odds of being at a high risk of SCD. The occurrence of an appropriate ICD therapy was significantly associated with being in the SP group, BMI, education level and TV/PC screen time. (4) Conclusions: Lifestyle and psychosocial factors have been confirmed to affect the risk of SCD. Early identification and treatment of coronary artery disease and its risk factors remain the cornerstones of preventive effort. Further research is needed to evaluate the complex nature of psychosocial determinants of cardiac health

Clinical utility of intracardiac echocardiography in transvenous lead extraction

The epidemics of heart failure and an aging population resulted in an exponential rise in the use of cardiac implantable devices (CIEDs) in developed countries. This is paralleled by the increased rate of complications such as system infection or malfunction. The higher number of complications, and longer patient life expectancies, are followed by an increase in the need for lead extractions.&nbsp

DNA damage and arterial hypertension. A systematic review and meta-analysis

Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P&lt;0.05 and="" 8ohdg="" 13="" 1="" 4="" 12="" vs="" 6="" 97="" 2="" 67="" ng="" mg="" creatinine="" i=""&gt; P&lt;0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P&lt;0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P&lt;0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P&lt;0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls