Risk Of Several Cardiovascular Diseases Research Articles

The Role of Gut Microbiota and Associated Compounds in Cardiovascular Health and its Therapeutic Implications.

It is possible that gut bacteria may have a beneficial effect on cardiovascular health in humans. It may play a major role in the progression of a variety of cardiovascular diseases, including Heart Failure (HF), Atherosclerosis, Coronary Arterial Disease (CAD), Ischemic Heart Disease (IHD), and Others. Dysbiosis of the gut microbiota, along with its direct and indirect impact on gut health, may induce cardiovascular disorders. Although advanced studies have demonstrated the relationship of various metabolites to cardiovascular diseases (CVD) in animals, translating their functional capacity to humans remains a significant area of research. This paper simplifies the demonstration of some compounds, pathways, and components like Trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and butyrate production. It demonstrates how a change in eating habits causes TMAO and how the impact of different drugs on gut microbiota species and high consumption of Westernized food causes several heartrelated problems, such as atherosclerosis and inflammation that can even become the cause of heart failure. Modulation of the gut microbiome, on the other hand, is a novel therapeutic measure because it can be easily altered through diet and other lifestyle changes. It could then be used to lower the risk of several CVDs.

Constipation is associated with an increased risk of major adverse cardiac events in a UK population.

Traditional cardiovascular risk factors, including hypertension, only explain part of major adverse cardiac events (MACEs). Understanding what other risk factors contribute to MACE is essential for prevention. Constipation shares common risk factors with hypertension and is associated with an increased risk of several cardiovascular diseases. We hypothesized that constipation is an underappreciated risk factor for MACE. We used the population healthcare and genomic data in the UK Biobank (n = 408,354) to study the contribution of constipation (ICD10 K59.0) to the risk of MACE, defined by any episode of acute coronary syndrome (ACS), ischemic stroke, and heart failure (HF). Analyses were controlled for traditional cardiovascular risk factors. We also assessed genetic correlations (rg) between constipation and MACE. Constipation cases (n = 23,814) exhibited a significantly higher risk of MACE compared with those with normal bowel habits [odds ratio (OR) = 2.15, P < 1.00 × 10-300]. Constipation was also significantly associated with individual MACE subgroups, in order: HF (OR = 2.72, P < 1.00 × 10-300), ischemic stroke (OR = 2.36, P = 2.02 × 10-230), and ACS (OR = 1.62, P = 5.82 × 10-113). In comparison with patients with constipation-free hypertension, patients with hypertension with constipation showed significantly higher odds of MACE (OR = 1.68, P = 1.05 × 10-136) and a 34% increased risk of MACE occurrence (P = 2.3 × 10-50) after adjustment for medications that affect gut motility and other traditional cardiovascular risk factors. Finally, we detected positive genetic correlations between constipation and MACE subgroups ACS (rg = 0.27, P = 2.12 × 10-6), ischemic stroke (rg = 0.23, P = 0.011), and HF (rg = 0.21, P = 0.0062). We identified constipation as a potential risk factor independently associated with higher MACE prevalence. These findings warrant further studies on their causal relationship and identification of pathophysiological mechanisms.NEW & NOTEWORTHY Analyzing 408,354 participants of the UK Biobank, we show that constipation cases exhibited a significantly higher risk of major adverse cardiac events (MACEs) than those with regular bowel habits. In comparison with patients with constipation-free hypertension, patients with hypertension with constipation showed significantly higher odds of MACE and a 34% increased risk of subsequent MACE occurrence. Finally, we detected positive genetic correlations between constipation and MACE. This association holds potential for therapeutic exploitation and prevention based on individuals' risk assessment.

U-shaped association between serum Klotho and all-cause mortality in US cardiovascular patients: a prospective cohort study.

Increased levels of serum Klotho have been associated with a reduced risk of several cardiovascular diseases (CVD). However, limited studies exist on the association between serum Klotho and mortality in patients with CVD. We collected data from CVD patients in the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2016. We linked NHANES data with the National Death Index to determine the survival status of participants. Univariate and multivariable Cox regression models were used to investigate the relationship between serum Klotho levels and mortality in CVD patients. The relationship between serum Klotho quartiles and mortality in CVD patients was visualized using Kaplan-Meier (KM) curves and restricted cubic spine. Finally, subgroup analyses were used to examine the association between serum Klotho and all-cause mortality in different populations. 1905 patients with CVD were finally enrolled in our study with a mean follow-up of 7.1 years. The average age of the participants was 63.4 years, with 58.40% being male. KM showed that lower Klotho levels were associated with lower survival rates. After adjusting for potential confounders, patients with higher serum Klotho levels had lower all-cause mortality (Q1: 1.00, Q2: 0.58 (0.42-0.80), Q3: 0.69 (0.47-1.01), and Q4:0.64 (0.45-0.92). However, the relationship between serum Klotho levels and cardiovascular mortality was not statistically significant. Dose-response analysis shows a U-shaped relationship between serum Klotho levels and all-cause mortality in patients with CVD (Pnonlinear=0.002). Subgroup analysis indicated that participants with a history of hypertension had a higher risk of all-cause mortality in serum Klotho Q4 compared to Q1 (P trend <0.05). The relationship between serum Klotho levels and all-cause mortality in CVD patients exhibits a U-shaped association. The underlying mechanisms of this association need further investigation.

Clinical Management of Non-alcoholic Steatohepatitis and the Role of the Cardiologist

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of fat-associated liver conditions that increase risk of cardiovascular disease and mortality. The diagnosis and clinical management of NAFLD remain a challenge for cardiologists. Our group performed a systematic review in PubMed of the relationship between NAFLD and cardiovascular disease, identifying 35 relevant articles. NAFLD is likely to be the liver’s expression of metabolic syndrome and increases the risk of several cardiovascular diseases, including coronary artery disease, stroke, heart failure and electrical disorders, and chronic kidney disease. Echocardiography is a useful tool to check early subclinical abnormalities in heart structure and function linked to NAFLD progression, such as cardiac diastolic impairment or epicardial fat thickness. Currently, NAFLD is predominantly managed by lifestyle changes with the aim of weight loss, based on the Mediterranean diet and intense exercise training. Despite the lack of approved drugs for NAFLD, new potential treatments, mainly glucagon-like peptide-1 agonists or sodium–glucose cotransporter 2 inhibitors, could change cardiologists’ approach to this pathology.

Nuts and Cardiovascular Disease Outcomes: A Review of the Evidence and Future Directions.

Nuts are nutrient-rich foods that contain many bioactive compounds that are beneficial for cardiovascular health. Higher consumption of nuts has been associated with a reduced risk of several cardiovascular diseases (CVD) in prospective cohort studies, including a 19% and 25% lower risk of CVD incidence and mortality, respectively, and a 24% and 27% lower risk of coronary heart disease incidence and mortality, respectively. An 18% lower risk of stroke mortality, a 15% lower risk of atrial fibrillation, and a 19% lower risk of total mortality have also been observed. The role of nuts in stroke incidence, stroke subtypes, peripheral arterial disease and heart failure has been less consistent. This narrative review summarizes recommendations for nuts by clinical practice guidelines and governmental organizations, epidemiological evidence for nuts and CVD outcomes, nut-containing dietary patterns, potential mechanisms of nuts and CVD risk reduction, and future research directions, such as the use of biomarkers to help better assess nut intake. Although there are still some uncertainties around nuts and CVD prevention which require further research, as summarized in this review, there is a substantial amount of evidence that supports that consuming nuts will have a positive impact on primary and secondary prevention of CVD.

Telomere length and the risk of cardiovascular diseases: A Mendelian randomization study.

The causal direction and magnitude of the associations between telomere length (TL) and cardiovascular diseases (CVDs) remain uncertain due to susceptibility of reverse causation and confounding. This study aimed to investigate the associations between TL and CVDs using Mendelian randomization (MR). In this two-sample MR study, we identified 154 independent TL-associated genetic variants from a genome-wide association study (GWAS) consisting of 472,174 individuals (aged 40-69) in the UK Biobank. Summary level data of CVDs were obtained from different GWASs datasets. Methods of inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), Mendelian Randomization robust adjusted profile score (MR-RAPS), maximum likelihood estimation, weighted mode, penalized weighted mode methods, and Mendelian randomization pleiotropy residual sum and outlier test (MR-PRESSO) were conducted to investigate the associations between TL and CVDs. Our findings indicated that longer TL was significantly associated with decreased risk of coronary atherosclerosis [odds ratio (OR), 0.85; 95% confidence interval (CI), 0.75-0.95; P = 4.36E-03], myocardial infarction (OR, 0.72; 95% CI, 0.63-0.83; P = 2.31E-06), ischemic heart disease (OR, 0.87; 95% CI, 0.78-0.97; P = 1.01E-02), stroke (OR, 0.87; 95% CI, 0.79-0.95; P = 1.60E-03), but an increased risk of hypertension (OR, 1.12; 95% CI, 1.02-1.23; P = 2.00E-02). However, there was no significant association between TL and heart failure (OR, 0.94; 95% CI, 0.87-1.01; P = 1.10E-01), atrial fibrillation (OR, 1.01; 95% CI, 0.93-1.11; P = 7.50E-01), or cardiac death (OR, 0.95; 95% CI, 0.82-1.10; P = 4.80E-01). Both raw and outlier corrected estimates from MR-PRESSO were consistent with those of IVW results. The sensitivity analyses showed no evidence of pleiotropy (MR-Egger intercept, P > 0.05), while Cochran's Q test and MR-Egger suggested different degrees of heterogeneity. Our MR study suggested that longer telomeres were associated with decreased risk of several CVDs, including coronary atherosclerosis, myocardial infarction, ischemic heart disease, and stroke, as well as an increased risk of hypertension. Future studies are still warranted to validate the results and investigate the mechanisms underlying these associations.

Self-reported symptoms of sleep-disordered breathing and risk of cardiovascular diseases: Observational and Mendelian randomization findings.

Sleep-disordered breathing may increase the risk of cardiovascular diseases, but observational findings are inconclusive. We investigated whether sleep-disordered breathing-related symptoms are associated with risk of several cardiovascular diseases using data from a cohort study and by performing Mendelian randomization analyses. The cohort study included 43,624 adults (56-94 years old) who completed questionnaires regarding symptoms of snoring and cessation of breathing, lifestyle habits and health characteristics. Participants were followed up for incident cardiovascular diseases and death over 8 years through linkage to the Swedish National Patient and Death Registers. The Mendelian randomization analyses were conducted using single-nucleotide polymorphisms robustly associated with sleep apnea in a recent genome-wide association study and summary-level data for major cardiovascular diseases from large-scale consortia. In the cohort study, an increased risk of atrial fibrillation was observed in participants who reported both snoring and cessation of breathing (hazard ratio [95% confidence interval]=1.16 [1.03-1.30]) compared with those without sleep-disordered breathing symptoms. There was no association between sleep-disordered breathing symptoms and risk of myocardial infarction, heart failure, aortic valve stenosis or abdominal aortic aneurysm in multivariable analyses. Mendelian randomization analyses showed no association of genetic liability to sleep apnea with myocardial infarction, heart failure or atrial fibrillation, but revealed a suggestive association with coronary artery disease (odds ratio [95% confidence interval]=1.24 [1.02-1.52]).

Hypertension and Cardiovascular Diseases among Electronic and Combustible Cigarette Users

IntroductionCombustible cigarette use is associated with an increased risk of several cardiovascular diseases; however, less is known about associations between these cardiovascular conditions and electronic cigarette use.MethodsThis study investigated relationships between electronic and/or combustible cigarette use and diagnoses of cardiovascular diseases using the National Health Interview Survey from 2014, 2016, 2017, and 2018.ResultsCompared to non-users, dual users of electronic and combustible cigarettes had increased likelihood of having prior diagnoses of hypertension (OR 1.660, 95% CI = 1.519–1.814), stroke (OR 2.396, 95% CI = 2.011–2.855), diabetes mellitus (OR 1.219, 95% CI = 1.108–1.341), coronary artery disease (OR 2.211, 95% CI = 1.837–2.660), and myocardial infarction (OR 3.839, 95% CI = 3.232–4.560). Exclusive use of electronic cigarettes was associated with an increased likelihood of having hypertension compared to non-users (OR 1.244, 95% CI = 1.048–1.477).ConclusionsThere were no differences in diagnoses of stroke, diabetes mellitus, coronary artery disease, or myocardial infarction among exclusive electronic cigarette users compared to non-users; however, these associations could change as young electronic cigarette users with hypertension age, indicating the need for continued research.

Glucagon-Like Peptide 1 Receptor Agonists: A Medication for Obesity Management.

The burden of obesity worldwide is high and projected to rise. Obesity increases the risk of several cardiovascular diseases and cardiometabolic risk factors; hence, utilizing effective long-term therapies for obesity is of utmost importance. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as effective therapies that achieve substantial weight loss and improve cardiometabolic risk. The purpose of this review is to discuss the role of GLP-1RAs in obesity management. Two subcutaneous GLP-1RAs, liraglutide and semaglutide, have been evaluated in several clinical trials for weight loss. Liraglutide achieves a mean weight loss of 4-7kg, and more than 50% of treated individuals achieve 5% or more weight loss. Semaglutide has a greater impact on weight loss, with a mean weight loss of 9-16kg, and more than 50% of treated individuals achieve 10-15% or more weight loss. These results led to regulatory approval of these agents for weight loss in individuals with obesity, regardless of diabetes status. In addition to weight loss, the benefits of GLP-1RAs extend to other risk factors, such as glycemic control and blood pressure. Gastrointestinal symptoms are the most frequently encountered adverse events with incidences between 5 and 30%. Finally, the cost remains one of the most critical challenges that limit GLP-1RAs use. GLP-1RAs have robust weight loss benefits and are expected to have a critical role in the management of obesity in the coming years. Upcoming studies will evaluate the durability of weight loss achieved with GLP-1RAs and the impact on cardiovascular outcomes.

Cardiovascular risk prediction: from classical statistical methods to machine learning approaches.

Nowadays, cardiovascular risk prediction scores are commonly used in primary prevention settings. Estimating the cardiovascular individual risk is of crucial importance for effective patient management and optimal therapy identification, with relevant consequences on secondary prevention settings. To reach this goal, a plethora of risk scores have been developed in the past, most of them assuming that each cardiovascular risk factor is linearly dependent on the outcome. However, the overall accuracy of these methods often remains insufficient to solve the problem at hand. In this scenario, machine learning techniques have repeatedly proved successful in improving cardiovascular risk predictions, being able to capture the non-linearity present in the data. In this concern, we present a detailed discussion concerning the application of classical versus machine learning-based cardiovascular risk scores in the clinical setting. This review aimed to give an overview of the current risk scores based on classical statistical approaches and machine learning techniques applied to predict the risk of several cardiovascular diseases, comparing them, discussing their similarities and differences, and highlighting their main drawbacks to aid the physician having a more critical understanding of these tools.

Aperçu sur les facteurs cardiométaboliques associés chez les patients atteints de la COVID-19 : une revue narrative

Coronavirus disease 2019 (COVID-19) increases the risk of several cardiovascular diseases (CVDs) such as acute myocardial injury. Vascular dysfunctions are important drivers of CVDs. A variety of risk factors promotes the development and progression of CVDs including, overweight and obesity, arterial hypertension, physical inactivity, smoking, unhealthy diet, overconsumption of alcohol, dyslipidemia, atherosclerosis and diabetes mellitus. However, nearly all of these risk factors are modifiable by antihypertensive, antidiabetic, or lipid-lowering medication and lifestyle changes. Other factors such as age or genetic factors cannot be modified. Moreover, infection and inflammation have been shown to increase the risk of CVDs. The COVID-19 pandemic yielded a new perspective to this field. Cardiometabolic events, diseases, risk factors and COVID-19 are strongly intertwined. An increased CVDs risk through multifactorial mechanisms has been observed in COVID-19 patients. Furthermore, a higher rate of infection with COVID-19, severe COVID-19, and bad outcome has been demonstrated in patients with established cardiometabolic disorders and vascular risk factors. Summary at present, we suggest that regular interactions between healthcare professionals and patients should include education on COVID-19 and on primary and secondary vascular prevention in order to minimize the burden of the virus in our susceptible populations. Keywords: Cardiometabolic disorders, cardiovascular diseases, inflammation, atherosclerosis, COVID-19.

Constipation and risk of cardiovascular diseases: a Danish population-based matched cohort study.

ObjectivesTo assess the risks of myocardial infarction, stroke, peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter and heart failure in patients with constipation compared with a general population cohort.DesignPopulation-based matched cohort study.SettingAll Danish hospitals and hospital outpatient clinics from 2004 to 2013.ParticipantsPatients with a constipation diagnosis matched on age, sex and calendar year to 10 individuals without constipation from the general population.Main outcomes measuresComorbidity-adjusted and medication-adjusted hazard ratios (aHRs) for cardiovascular outcomes based on Cox regression analysis.Results83 239 patients with constipation were matched to 832 384 individuals without constipation. The median age at constipation diagnosis was 46.5% and 41% were men. Constipation was strongly associated with venous thromboembolism (aHR 2.04, 95% CI 1.89 to 2.20), especially splanchnic venous thrombosis (4.23, 95% CI 2.45 to 7.31). Constipation was also associated with arterial events, including myocardial infarction (1.24, 95% CI 1.14 to 1.35), ischaemic stroke (1.50, 95% CI 1.41 to 1.60), haemorrhagic stroke (1.46, 95% CI 1.26 to 1.69), peripheral artery disease (1.34, 95% CI 1.20 to 1.50), atrial fibrillation or atrial flutter (1.27, 95% CI 1.20 to 1.34) and heart failure (1.52, 95% CI 1.42 to 1.62). The associations were strongest during the first year after the constipation diagnosis and strengthened with an increased number of laxative prescriptions.ConclusionsConstipation was associated with an increased risk of several cardiovascular diseases, in particular venous thromboembolism.

SUN-618 Decision Analysis for Glucagon-Like Peptide Receptor Agonists vs. Sodium-Glucose cotransporter2 Inhibitors in Type 2 Diabetes Mellitus

Background: Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD), and renal outcomes (RO). Objective. Evaluation of data to assist in the prescribing decision with regard to severity of illness and risk for adverse events. Study Design: Systemic review of the major CVOT and previous meta-analyses. Main Outcome Measures: Analysis of six trials on GLP-1 RA and 4 trials on SGLT2i, showed both drug classes reduced MACE and CVD compared to controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: (relative rate, rr MACE= 1.09, 95%CI;0.98,1.22, p= 0.129; rr, CVD =1.04, CI;0.87,1.24, p=0.657). Hospitalization for heart failure (HHF) improved with SGLT2i (rr=0.68, CI; 0.61,0.76, p<0.001) but not with GLP-1 RA, (rr = 0.94, CI; 0.86,1.03, p=0.17). Both GLP-1 RA and SGLT2i showed significant reduction in RO (GLP-1RA, rr=0.83, CI; 0.75,0.912, p=<0.001, SGLT2i, rr=0.0.67, CI; 0.57,0.79, p=0.001) without a preferential difference between the classes (GLP-1 RA vs SGLT2i, relative difference (rd) =0.005, CI;-0.011,0.021, p=0.532, number needed to treat (NNT)=200). Serious adverse events (SAE) for SGLT2i were predominantly mycotic genital infections in women (number needed to harm (NNH) =13 and diabetic ketoacidosis NNH=595. Gastrointestinal intolerance was the major SAE in the GLP1-RA class (NNH=35). Conclusion: Both GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and RO. SGLT2i have advantages over GLP-1 RA in reduction in HHF especially in those with more severe cardiovascular disease risk.

Relationship between urinary bisphenol a levels and cardiovascular diseases in the U.S. adult population, 2003-2014.

Emerging evidence has identified cardiovascular system as a potential target of Bisphenol A (BPA). Although a few studies have revealed the relationship between BPA and the risk of several cardiovascular diseases (CVD) outcomes and CVD risk factors, no published studies have investigated the link between urinary BPA and the risk of stroke. Data were derived from the United States National Health and Nutrition Examination Surveys (NHANES), with a representative sample aged ≥20 years (n=9139) from 2003 to 2014. We performed multivariable logistic regression model to estimate associations between quartiles and natural logarithm transformed urinary BPA concentrations and five specific CVD outcomes and total CVD. In quartile analysis, highest level of urinary BPA was associated with increased prevalence of myocardial infarction (MI) (OR=1.73, 95% CI=1.11-2.69) and stroke (OR=1.61, 95% CI=1.09-2.36), when compared with those at the lowest quartile. Per unit (μg/g creatinine) increment in ln-transformed BPA concentration was shown to be significantly associated with 19%, 19%, 25%, 29%, 20%, and 16% increased odds ratios of prevalence of congestive heart failure, coronary heart disease (CHD), angina pectoris, MI, stroke and total CVD among total participants, respectively. Similar associations were found in males rather than in females. We provided the premier evidence of positive relationship between urinary BPA concentration and stroke in U.S. Urinary BPA levels were also positively correlated with congestive heart failure, CHD, angina pectoris, MI, as well as total CVD. These associations were more evident in males. Well-coordinated and prospective studies are warranted to gain the human effects of BPA on CVD.

Associations of air pollution with hypertension, heart attack and stroke morbidity in a large national health survey

Introduction: Exposure to air pollution has been associated with an increased risk of several cardiovascular diseases. Most studies so far focused on associations with mortality, less is known abou...

Effects of ethanol on red blood cell rheological behavior

Consumption of red wine is associated with a decreased risk of several cardiovascular diseases (e.g., coronary artery disease, stroke), but unfortunately literature reports regarding ethanol's effects on hemorheological parameters are not concordant. In the present study, red blood cell (RBC) deformability was tested via laser ektacytometry (LORCA, 0.3-30 Pa) using two approaches: 1) addition of ethanol to whole blood at 0.25%-2% followed by incubation and testing in ethanol-free LORCA medium; 2) addition of ethanol to the LORCA medium at 0.25%-6% then testing untreated native RBC in these media. The effects of ethanol on deformability for oxidatively stressed RBC were investigated as were changes of RBC aggregation (Myrenne Aggregometer) for cells in autologous plasma or 3% 70 kDa dextran. Significant dose-related increases of RBC deformability were observed at 0.25% (p < 0.05) and higher concentrations only if ethanol was in the LORCA medium; no changes occurred for cells previously incubated with ethanol then tested in ethanol-free medium. The impaired deformability of cells pre-exposed to oxidative stress was improved only if ethanol was in the LORCA medium. RBC aggregation decreased with concentration at 0.25% and higher for cells in both autologous plasma and dextran 70. Our results indicate that ethanol reversibly improves erythrocyte deformability and irreversibly decreases erythrocyte aggregation; the relevance of these results to the health benefits of moderate wine consumption require further investigation.

Contribution of arginase activation to vascular dysfunction in cigarette smoking

BackgroundCigarette smoke increases the risk of several cardiovascular diseases and has synergistic detrimental effects when present with other risks that contribute to its pathogenesis. Oxidative injury to the endothelium via reactive oxygen species (ROS) and nitric oxide (NO) dysregulation is a common denominator of smoking-induced alterations in vascular function. However, the mechanisms underlying ROS and NO dysregulation due to smoking remain unclear. We tested if arginase (Arg) activation/upregulation contributes to this phenomenon by constraining nitric oxide synthase (NOS) activity. MethodsArg2 knockout (Arg2−/−) and control C57BL/6J mice were either exposed to cigarette smoke, 6 h/day/2 weeks (Second Hand Smoking; SHS) or housed in normal environment (Non Smoking; NS). Arg activity, NO and ROS levels were determined by measuring urea production, fluorescent dye (DAF), and dihydroethedium (DHE) respectively in isolated mouse aorta. ResultsArg activity and ROS levels were higher NO lower in SHS compared to NS mice. SHS failed to lower NO levels in Arg2−/− mice. Endothelial dependent vasodilation (EDV) was attenuated in SHS mice as compared to controls (78.80% ± 8 vs 46.58% ± 5). This impaired EDV was abolished in Arg2−/− mice (67.48% ± 7 in SHS vs. 78.80% ± 8 in NS). Vascular stiffness was increased in SHS mice as compared to NS controls but remained unchanged in Arg2−/− mice. ConclusionEndothelial NOS is uncoupled by smoking exposure, leading to endothelial dysfunction and vascular stiffness, a process that is prevented by Arg2 deletion. Hence, we identify Arg2 upregulation as a critical pathogenic factor and target for therapy in oxidative injury following smoking exposure through reciprocal regulation of endothelial NOS.

Risk of cardiovascular disease in family members of young sudden cardiac death victims

Descriptive and genetic studies suggest that relatives of sudden cardiac death (SCD) victims have an increased risk of several cardiovascular diseases (CVDs). Given the severe consequences of undiagnosed CVD and the availability of effective treatment, the potential for prevention in this group is enormous if they do have an increased CVD risk. This nationwide prospective population-based cohort study described the risk of CVDs in relatives of young SCD victims, compared with the general population. All SCD victims aged 1-35 years in Denmark, 2000-2006, were identified (n = 470), along with their first- and second-degree relatives (n = 3073). We compared the incidence of CVD in those relatives with that in the background population using standardized incidence ratios (SIRs). The observed number of CVDs over 11 years of follow-up was 292, compared with 219 expected based on national rates [SIR 1.33, 95% confidence interval (CI) 1.19-1.50]. Risks varied significantly with age; the SIR for those <35 years was 3.53 (95% CI 2.65-4.69), compared with SIRs of 1.59 (95% CI 1.35-1.89) and 0.91 (95% CI 0.75-1.10) for those aged 35-60 years or >60 years, respectively (P(homogeneity) < 0.0001). For first-degree relatives <35 years, SIRs for ischaemic heart disease, cardiomyopathy, and ventricular arrhythmia were 5.99 (95% CI 1.95-0.13.98), 17.91 (95% CI 4.88-45.87), and 19.15 (95% CI 7.70-39.45), respectively. CVDs co-aggregated significantly with SCD in families, with young first-degree relatives at greatest risk. Results clearly indicate that family members of young SCD victims should be offered comprehensive and systematic screening, with focus on the youngest relatives.

Ambulatory blood pressure monitoring in Australia

Although most national guidelines for the diagnosis and management of hypertension emphasize that the initiation and modification of blood pressure (BP)-lowering treatment should be related to absolute cardiovascular disease (CVD) risk, there is only limited information on how to incorporate ambulatory BP (ABP) monitoring into this framework. The objective of this initiative is to provide ABP equivalents for BP cut-points for treatment initiation and targets to be included into guidelines. A critical analysis of the best available evidence from clinical trials and observational studies was undertaken to develop a new consensus statement for ABP monitoring. ABP monitoring has an important place in defining abnormal patterns of BP, particularly white-coat hypertension (including in pregnancy), episodic hypertension, masked hypertension, labile BP and nocturnal or morning hypertension. This consensus statement provides a framework for appropriate inclusion of ABP equivalents for low, moderate and high CVD risk patients. The wider use of ABP monitoring, although justified, is limited by its availability and cost due to the lack of medical subsidy in Australia. However, cost-benefit analysis does suggest a cost-saving in reduced numbers of inappropriate antihypertensive treatments. Although clinic measurement of BP will continue to be useful for screening and management of suspected and true hypertension, ABP monitoring provides considerable added value toward accurate diagnosis and the provision of optimal care in uncomplicated hypertension, as well as for patients with moderate or severe CVD risk.

Physio-pathological effects of alcohol on the cardiovascular system: its role in hypertension and cardiovascular disease

Alcohol has complex effects on the cardiovascular system. The purpose of this article is to review physio-pathological effects of alcohol on cardiovascular and related systems and to describe its role in hypertension and cardiovascular disease. The relationship between alcohol and hypertension is well known, and a reduction in the alcohol intake is widely recommended in the management of hypertension. Moreover, alcohol has both pressor and depressor actions. The latter actions are clear in Oriental subjects, especially in those who show alcohol flush because of the genetic variation in aldehyde dehydrogenase activity. Repeated alcohol intake in the evening causes an elevation in daytime and a reduction in nighttime blood pressure (BP), with little change in the average 24-h BP in Japanese men. Thus, the hypertensive effect of alcohol seems to be overestimated by the measurement of casual BP during the day. Heavy alcohol intake seems to increase the risk of several cardiovascular diseases, such as hemorrhagic stroke, arrhythmia and heart failure. On the other hand, alcohol may act to prevent atherosclerosis and to decrease the risk of ischemic heart disease, mainly by increasing HDL cholesterol and inhibiting thrombus formation. A J- or U-shaped relationship has been observed between the level of alcohol intake and risk of cardiovascular mortality and total mortality. It is reasonable to reduce the alcohol intake to less than 30 ml per day for men and 15 ml per day for women in the management of hypertension. As a small amount of alcohol seems to be beneficial, abstinence from alcohol is not recommended to prevent cardiovascular disease.