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The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as 'free-floating' in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease.

Background: Previous studies showed that troponin blood levels may increase after exercise. In this study we assessed whether, among patients admitted with suspected unstable angina, the increase in high-sensitive troponin T (hs-TnT) levels after exercise stress test (EST) might help identify those with obstructive coronary artery disease (CAD) and predict symptom recurrence during short term follow-up. Methods: Maximal treadmill EST was performed in 69 consecutive patients admitted to the emergency room with a suspicion of unstable angina (acute chest pain but confirmed normal serum levels of cardiac troponins) was measured before and 4 hours after EST. Coronary angiography was performed in 22 patients (32.8%). Results: hs-TnT increased after EST compared to baseline in the whole population (from 0.84±0.65 to 1.17±0.87 ng/dL, p<0.001). The increase was similar in patients with positive (n = 14) and negative (n = 55) EST (p = 0.72), and was also similar in patients with (n = 12) and without (n = 10) obstructive CAD at angiography (p = 0.91). The achievement of a heart rate at peak EST ≥85% of that predicted for age was the variable mainly associated with the post-EST hs-TnT increase at multivariable linear regression analysis (p = 0.005). The change after EST of hs-TnT did not predict the recurrence of symptoms or readmission for chest pain at 6-month follow-up. Conclusions: Our data show that hs-TnT increased after EST in patients with suspected unstable angina, which seemed largely independent of most clinical and laboratory variables. Thus, hs-TnT assessed after EST does not seem to be helpful to identify patients with obstructive CAD in this kind of patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether exposure to hyperemesis gravidarum (hyperemesis) is associated with subsequent maternal cardiovascular morbidity. Design: Nationwide cohort study. Setting: Medical Birth Registry of Norway (1967–2002) linked to the nationwide Cardiovascular Disease in Norway project 1994–2009 (CVDNOR) and the Cause of Death Registry. Population: Women in Norway with singleton births from 1967 to 2002, with and without hyperemesis, were followed up with respect to cardiovascular outcomes from 1994 to 2009. Methods: Cox proportional hazards regression model was applied to estimate hazard ratios (HRs) with 95% confidence interval (CI). Main outcome measures: The first hospitalisation due to nonfatal stroke, myocardial infarction or angina pectoris, or cardiovascular death. Results: Among 989 473 women with singleton births, 13 212 (1.3%) suffered from hyperemesis. During follow-up, a total of 43 482 (4.4%) women experienced a cardiovascular event. No association was found between hyperemesis and the risk of a fatal or nonfatal cardiovascular event (adjusted HR 1.08; 95% CI 0.99–1.18). Women with hyperemesis had higher risk of hospitalisation due to angina pectoris (adjusted HR 1.28; 95% CI 1.15–1.44). The risk of cardiovascular death was lower among hyperemetic women in age-adjusted analysis (HR 0.73; 95% CI 0.59–0.91), but the association was no longer significant when adjusting for possible confounders. Conclusion: Women with a history of hyperemesis did not have increased risk of a cardiovascular event (nonfatal myocardial infarction or stroke, angina pectoris or cardiovascular death) compared to women without. [ABSTRACT FROM AUTHOR]

Background: A link between angina with no obstructive coronary artery disease (CAD) and heart failure with preserved left ventricular ejection fraction has been proposed, but evidence in support of this is lacking. In a cross-sectional study, we investigated whether left ventricular diastolic function in women with angina pectoris and no obstructive CAD differed from a reference population. Methods: We included 956 women with angina and <50% coronary artery stenosis at invasive coronary angiography. Women with cardiovascular risk factors, but no history of chest pain or cardiac disease served as controls (n = 214). Left ventricular diastolic function was assessed by transthoracic echocardiography. Results: The women with angina were slightly older, had higher body mass index, higher heart rate, and more had diabetes compared with controls while systolic blood pressure was lower. In age-adjusted analyses, angina patients had significantly lower E/A (Estimated difference -0.13, 95% CI: -0.17; -0.08), higher left ventricular mass index (5.73 g/m2, 95% CI: 3.71; 7.75), left atrial volume index (2.34 ml/m2, 95% CI: 1.23; 3.45) and E/e’ (0.68, 95% CI: 0.30; 1.05) and a larger proportion had higher estimated left ventricular filling pressure (17% versus 6%, p = 0.001). No between group differences were seen for e’ or deceleration time. After adjustment for known cardiovascular risk factors, between group differences for echocardiographic parameters remained statistically significant. Conclusions: Patients with angina and no obstructive CAD had a more impaired left ventricular diastolic function compared with an asymptomatic reference population. This suggests some common pathophysiological pathway between the two syndromes. [ABSTRACT FROM AUTHOR]

Background: The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography. Methods: 1599 individuals (mean age 64 years [min-max 29–96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010–2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies. Results: Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p<0.0001) earlier need of revascularization in sex-adjusted models. Patients with and without familial CAD had similar mean values of CAD-GRS (unweighted scores 68.4 vs. 68.0, p = 0.10, weighted scores 67.7 vs. 67.5, p = 0.49) and LDL-C-GRS (unweighted scores 58.5 vs. 58.3, p = 0.34, weighted scores 63.3 vs. 61.1, p = 0.41). The correlation between the CAD-GRS and LDL-C-GRS was low (r = 0.14, p<0.001). In multivariable adjusted regression models, each 1 standard deviation higher values of LDL-C-GRS and CAD-GRS were associated with -0.70 years (95% confidence interval -1.25, -0.14, p = 0.014) and -0.51 years (-1.07, 0.04, p = 0.07) earlier need for revascularization, respectively. Conclusions: Young individuals presenting with CAD requiring surgical interventions had a higher genetic burden of SNPs relating to LDL-C and CAD (although the latter was statistically non-significant), compared with older individuals. However, the absolute difference was modest, suggesting that genetic screening can currently not be used as an effective prediction tool of when in life a person will develop CAD. Whether undiscovered genetic variants can still explain a “missing heritability” in early-onset CAD warrants more research. [ABSTRACT FROM AUTHOR]

There is conflicting evidence for the clinical benefit of statin therapy in patients with vasospastic angina (VSA). We investigated the association of statin therapy with clinical outcomes in relatively large populations with clinically suspected VSA from a nationwide population-based database. Data were collected from the Health Insurance Review and Assessment database records of 4,099 patients that were in an intensive care unit with VSA between January 1, 2008 and May 31, 2015. We divided the patients into a statin group (n = 1,795) and a non-statin group (n = 2,304). The primary outcome was a composite of cardiac arrest and acute myocardial infarction (AMI). The median follow-up duration was 3.8 years (interquartile range: 2.2 to 5.8 years). Cardiac arrest or AMI occurred in 120 patients (5.2%) in the statin group, and 97 patients (5.4%) in the non-statin group (P = 0.976). With inverse probability of treatment weighting, there was no significant difference in the rate of cardiac arrest or AMI between the two groups (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.76–1.30; P = 0.937), or even between the non-statin group and high-intensity statin group (adjusted HR, 1.08; 95% CI, 0.69–1.70; P = 0.75). The beneficial association of statin use with the primary outcome was consistently lacking across the various comorbidity types. Statin therapy was not associated with reduced cardiac arrest or AMI in patients with VSA, regardless of statin intensity. Prospective, randomized trials will be needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Objectives: Despite an obvious improvement in the treatment of coronary artery disease (CAD) and survival rate of patients with CAD during recent decades, diabetes mellitus (DM) is still considered a risk factor of adverse clinical outcomes in these patients. Therefore, we sought to evaluate the clinical implications of DM in patients with CAD who underwent contemporary percutaneous coronary intervention (PCI). Methods: Based on the National Health Insurance claims data in South Korea, patients aged 18 years or older who had undergone PCI for the diagnosis of CAD between 2011 and 2015 were analyzed. Patients were classified into the DM (n = 26,872) and non-DM (n = 54,243) groups. The primary endpoint was all-cause mortality, and it was compared between the two groups via a propensity score matching analysis. Results: The study population was categorized as patients with angina (n = 49,228) or acute myocardial infarction (AMI, n = 31,887). The study population had a median follow-up of 2.1 years (interquartile range, 1.1–3.2). After the propensity score matching analysis, 8,157 and 4,266 pairs of patients with angina and AMI were identified, respectively. In the matched angina group, the incidence of all-cause death was significantly higher in patients with DM (adjusted hazard ratio [aHR]: 1.30; 95% confidence interval [CI]: 1.16–1.47; p<0.001) than in those without DM. Moreover, in the matched AMI group, the incidence of all-cause death was significantly higher in patients with DM (aHR: 1.35; 95% CI: 1.19–1.53; p<0.001) than in those without DM. Conclusions: In patients undergoing contemporary PCI in Korea, the presence of DM was associated with poorer clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: It is unclear whether high-intensity statin therapy provides incremental clinical benefits over moderate-intensity statin therapy in Asian patients with angina. This study sought to compare the clinical outcomes of moderate- and high-intensity statin therapies in patients undergoing percutaneous coronary intervention (PCI) for angina in Korean patients. Methods: Based on the national health insurance claims data in South Korea, patients aged 18 years or older without a known history of coronary artery disease, who underwent PCI with drug-eluting stents due to angina between 2011 and 2015, were enrolled. According to the intensity of statin therapy, patients were categorized into moderate-intensity statin therapy (n = 23,863) and high-intensity statin therapy (n = 9,073) groups. The primary endpoint, defined as a composite of all-cause death and myocardial infarction, was compared between the two groups using a propensity-score matching analysis. Results: During the follow-up period (median, 2.0 years; interquartile range, 1.1–3.1), 1,572 patients had 1,367 deaths and 242 myocardial infarctions. After propensity-score matching, there were 8,939 matched pairs. There was no significant difference in the incidence of the primary endpoint between the two groups (adjusted hazard ratio of high-intensity statin therapy, 1.093; 95% confidence interval: 0.950–1.259; p = 0.212). Conclusions: In Korean patients undergoing PCI with drug-eluting stents for angina, the high-intensity statin therapy did not provide additional clinical benefits over the moderate-intensity statin therapy. [ABSTRACT FROM AUTHOR]

Background: We evaluated optimal duration of dual antiplatelet therapy (DAPT) after second-generation drug-eluting stent (DES) implantation in acute coronary syndrome (ACS). Material and methods: From pooled analysis of three randomized clinical trials (EXCELLENT, IVUS-XPL, RESET), a total of 2,216 patient with ACS undergoing second-generation DES implantation were selected. Each study randomized patients to a short-duration DAPT arm (n = 1119; ≤6 months) or a standard-duration DAPT arm (n = 1097; ≥12 months). Two-thirds of patients were male, and their mean age was 63 years. Mean DAPT durations were 164 ±76 and 359 ±68 days, respectively. The primary endpoint was composite of cardiac death, myocardial infarction, stent thrombosis, stroke or major bleeding during the first 12 months after implantation, analyzed according to the intention-to-treat population. Results: Demographic characteristics were balanced between groups. Mean DAPT duration was 164 and 359 days, respectively. Primary endpoint occurred in 22 patients with short-DAPT and 21 patients with standard-DAPT (2.0% versus 1.9%; hazard ratio [HR] 1.03; 95% confidence interval [CI] 0.56–1.86; p = 0.94). Landmark analysis after six-months, no significant difference in primary endpoint between short and standard duration DAPT (1.0% versus 0.8%; HR 1.22; 95% CI 0.51–2.95; p = 0.66). Conclusions: Short-duration DAPT (≤6 months) demonstrated a similar incidence of net adverse cardiovascular and clinical events at 12 months after second-generation DES in ACS compared with standard duration DAPT (≥12 months). Clinical trial registration: EXCELLENT (ClinicalTrials.gov, ), RESET (ClinicalTrials.gov, ), IVUS-XPL (ClinicalTrials.gov, ) [ABSTRACT FROM AUTHOR]

Introduction: In patients with psoriatic arthritis (PsA) an increased cardiovascular (CV) risk has been observed. Recently, a EULAR taskforce suggested to use a multiplication by the factor of 1.5 of CV risk algorithms in patients with inflammatory arthritis. This study aims to evaluate the performance of five original and adapted according to EULAR recommendations CV risk algorithms in PsA: SCORE, CUORE, Framingham Risk Score (FRS), QRISK2, and Reynold’s Risk Score (RRS). Methods: Prospectively collected data from two Italian cohorts were used. Discriminatory ability for CV risk prediction was evaluated by the area under the ROC curves. Calibration between predicted and observed events was assessed by Hosmer-Lemeshow (HL) tests. Sensibility and specificity were calculated for low-to-intermediate and intermediate-to-high risk cut-offs. Results: One hundred fifty-five patients were enrolled with an observation of 1550 patient/years. Area under the ROC were 0.7679 (95% CI 0.64768 to 0.88812), 0.864 (95% CI 0.79675 to 0.93278), 0.7575 (95% CI 0.65784 to 0.85708), 0.8660 (95% CI 0.79428 to 0.93772), and 0.7183 (95% CI 0.57795 to 0.85862) for SCORE, CUORE, FRS, QRSIK2, and RRS, respectively. HL tests demonstrated poor model fit (p<0.05) for SCORE, CUORE, and RRS. Discriminative ability and calibration were not improved by adaption of the algorithms according to EULAR recommendations. Up to 80% of CV events occurred in patients at “low risk” and up to 93% of CV events in patients at “low-intermediate risk”. Conclusions: Adaption of the CV risk algorithms according to EULAR indications did not provide improvement in discriminative ability and calibration in patients with PsA. [ABSTRACT FROM AUTHOR]

Background: In systemic lupus erythematosus (SLE), cardiac manifestations, e.g. coronary artery disease (CAD) and myocarditis are leading causes of morbidity and mortality. The prevalence of subclinical heart disease in SLE is unknown. We studied whether a comprehensive cardiovascular magnetic resonance (CMR) protocol may be useful for early diagnosis of heart disease in SLE patients without known CAD. Methods: In this prospective, observational, cross-sectional study CMR including cine, late gadolinium enhancement (LGE) and stress perfusion sequences, ECG, and blood sampling were performed in 30 consecutive SLE patients without known CAD. All patients fulfilled at least 4/11 American College of Rheumatology (ACR) Criteria for the classification of SLE. Results: 30 patients (83% female) were enrolled, mean age was 45±14 years and mean SLE disease duration was 10±8 years. 80% had low to moderate disease activity. All had a low SLE damage index. CMR was abnormal in 13/30 (43%), showing LGE in 9/13, stress perfusion deficits in 5/13 and pericardial effusion (PE) in 7/13. Patients with non-ischemic LGE had more often microalbuminuria while patients with stress perfusion deficits a history of hypertension, renal disorder as ACR criterion, repolarisation abnormalities on ECG and larger LV enddiastolic volume index. There was no correlation between clinical symptoms and CMR results. Conclusion: Our study shows that cardiac involvement as observed by CMR is frequent in SLE and not necessarily associated with typical symptoms. CMR may thus help to detect subclinical cardiac involvement, which could lead to earlier treatment. Additionally we identify possible risk factors associated with cardiac involvement. [ABSTRACT FROM AUTHOR]

Prognostic modelling is important in clinical practice and epidemiology for patient management and research. Electronic health records (EHR) provide large quantities of data for such models, but conventional epidemiological approaches require significant researcher time to implement. Expert selection of variables, fine-tuning of variable transformations and interactions, and imputing missing values are time-consuming and could bias subsequent analysis, particularly given that missingness in EHR is both high, and may carry meaning. Using a cohort of 80,000 patients from the CALIBER programme, we compared traditional modelling and machine-learning approaches in EHR. First, we used Cox models and random survival forests with and without imputation on 27 expert-selected, preprocessed variables to predict all-cause mortality. We then used Cox models, random forests and elastic net regression on an extended dataset with 586 variables to build prognostic models and identify novel prognostic factors without prior expert input. We observed that data-driven models used on an extended dataset can outperform conventional models for prognosis, without data preprocessing or imputing missing values. An elastic net Cox regression based with 586 unimputed variables with continuous values discretised achieved a C-index of 0.801 (bootstrapped 95% CI 0.799 to 0.802), compared to 0.793 (0.791 to 0.794) for a traditional Cox model comprising 27 expert-selected variables with imputation for missing values. We also found that data-driven models allow identification of novel prognostic variables; that the absence of values for particular variables carries meaning, and can have significant implications for prognosis; and that variables often have a nonlinear association with mortality, which discretised Cox models and random forests can elucidate. This demonstrates that machine-learning approaches applied to raw EHR data can be used to build models for use in research and clinical practice, and identify novel predictive variables and their effects to inform future research. [ABSTRACT FROM AUTHOR]

Introduction: Postprandial hyperglycemia plays a pivotal role in cardiovascular disease. However, few studies have investigated associations between the severity of coronary artery disease (CAD) and postprandial glucose levels in angina patients without known diabetes before coronary angiography. Methods: Subjects who were admitted for coronary angiography due to angina and were in stable condition after discharge were recruited. A standard 75-g oral glucose tolerance test (OGTT) was performed at outpatient visits approximately 2–4 weeks after hospital discharge, and fasting and post-challenge blood glucose were measured. Twenty-six volunteers in our hospital staff served as the healthy group. CAD severity was graded using the SYNTAX and Jeopardy scoring systems. Results: The subjects in the angina group had a higher body mass index, higher fasting glucose, and higher 2-h postprandial glucose than those in the healthy group. The SYNTAX and Jeopardy scores were significantly associated with 2-h postprandial blood glucose (correlation coefficients = 0.164 and 0.187, respectively) but not with fasting glucose. Linear regression analyses revealed that SYNTAX and Jeopardy scores were independently associated with glucose levels at 120 min after OGTT (SYNTAX 95%CI = 0.003–0.103; Jeopardy score 0.002–0.027) but not with fasting glucose. Conclusion: CAD severity is associated with blood glucose levels after oral glucose challenge in patients without known diabetes before coronary angiography, suggesting that CAD patients should be routinely screened for post-challenge blood glucose. [ABSTRACT FROM AUTHOR]

Objectives: Bilateral internal thoracic artery (ITA) grafting is associated with improved survival. However, potential survival benefit of using two ITA`s in patients with chronic lung disease (CLD) is questionable due to their increased risk of sternal wound infection (SWI) compared to operations incorporating single ITA (SITA). The purpose of this study is to compare early and long-term outcome of bilateral internal thoracic artery (BITA) grafting to that of grafting with single internal thoracic grafts and vein grafts or radial artery (SITA) in CLD patients with multi-vessels coronary disease. Methods: One hundred and forty eight CLD patients who underwent BITA between 1996 and 2011 were compared with 239 who underwent SITA at the same period. Results: SITA patients were more often female, more likely to have insulin treated diabetes (DM), DM with end organ damage, neurologic dysfunction and unstable angina. Despite of the difference in preoperative characteristics, early mortality (5.4% vs. 5.4%, in the SITA and BITA respectively, p = 0 < .999) and occurrences of SWI (6.3% vs 9.5%, p = 0.320) and strokes (3.8% vs 5.4%,p = 0.611) were not significantly different between groups. BITA patients did not have better Kaplan-Meier 10 year survival (52.8% vs. 42.6%, p = 0.088) and after matching, BITA and SITA had similar adjusted survival (HR 0.983[95%CI 0.755–1.280] p = 0.901) (cox model). Conclusion: Our study results suggest that in patients with CLD, the choice of BITA grafting technique did not provide survival benefit compared to SITA with other conduits. [ABSTRACT FROM AUTHOR]

Data on contemporary management patterns of angina in patients with stable coronary artery disease (CAD) are scarce. We sought to describe the current presentation, management, and quality of life of stable CAD patients with or without angina, using the data from the START (STable Coronary Artery Diseases RegisTry) study. START was a prospective, observational, nationwide study aimed to evaluate the presentation, management, treatment and quality of life of stable CAD presenting to cardiologists during outpatient visits or discharged from cardiology wards. Among the 5070 consecutive stable CAD patients enrolled in 183 participating centers over a 3-month period, 3714 (73.2%) had no angina and 1356 (26.8%) presented with angina. Patients with angina underwent more frequently coronary angiography (92.7% vs 84.9%; p<0.0001) and other diagnostic imaging procedures compared to those without angina. In addition, patients with angina received more frequently different combinations of first line therapies and angina relief drugs compared to patients without angina. The quality of life, assessed with the EQ 5D-5L questionnaire, did not differ between the two groups, with the exception of the ‘pain or worry’ domain that was higher in patients with compared to those without angina (p<0.0001). Current management and treatment of stable CAD patients with angina is still suboptimal and different compared to those without angina. Our findings highlight the need for disseminating best-practice patterns and improving guidelines adherence for the management of angina even among cardiologists. [ABSTRACT FROM AUTHOR]

Risk stratification in secondary prevention has emerged as an unmet clinical need in order to mitigate the Number-Needed-to-Treat and make expensive therapies both clinically relevant and cost-effective. P wave indices reflect atrial conduction, which is a sensitive marker for inflammatory, metabolic, and pressure overload myocardial cell remodeling; the three stimuli are traditional mechanisms for adverse clinical evolution. Accordingly, we sought to investigate the predictive role of P-wave indices to estimate residual risk in patients with chronic coronary artery disease (CAD). The cohort included 520 post-Coronary Artery Bypass Grafting patients with a median age of 60 years who were followed for a median period of 1025 days. The primary endpoint was long-term all-cause death. Cubic spline model demonstrated a linear association between P-wave duration and incidence rate of long-term all-cause death (p = 0.023). P-wave >110ms was a marker for an average of 425 days shorter survival as compared with P-wave under 80ms (Logrank p = 0.020). The Cox stepwise regression models retained P-wave duration as independent marker (HR:1.37; 95%CI:1.05–1.79,p = 0.023). In conclusion, the present study suggests that P-wave measurement may constitute a simple, inexpensive and accessible prognostic tool to be added in the bedside risk estimation in CAD patients. [ABSTRACT FROM AUTHOR]

Background: Unrecognized myocardial infarctions (UMIs) are common. The study is an extension of a previous study, aiming to investigate the long-term (>5 year) prognostic implication of late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) detected UMI in patients with suspected stable coronary artery disease (CAD) without previously diagnosed myocardial infarction (MI). Methods: In 235 patients with suspected stable CAD without previous MI, LGE-CMR imaging and coronary angiography were performed. LGE with a subendocardial component detectable in more than one imaging plane was required to indicate UMI. The stenosis grade of the coronary arteries was determined, including in the artery supplying an infarcted area. Stenosis ≥70% stenosis was considered significant. Patients were followed for 5.4 years in mean regarding a composite endpoint of cardiovascular death, MI, hospitalization due to heart failure, stable or unstable angina. Results: UMI were present in 58 of 235 patients (25%). Thirty-nine of the UMIs were located downstream of a significant coronary stenosis. During the follow-up 40 patients (17.0%) reached the composite endpoint. Of patients with UMI, 34.5% (20/58) reached the primary endpoint compared to 11.3% (20/177) of patients with no UMI (HR 3.7, 95% CI 2.0–6.9, p<0.001). The association between UMI and outcome remained (HR 2.3, 95% CI 1.2–4.4, p = 0.012) after adjustments for age, gender, extent of CAD and all other variables univariate associated with outcome. Sixteen (41%) of the patients with an UMI downstream of a significant stenosis reached the endpoint compared to four (21%) patients with UMI and no relation to a significant stenosis (HR 2.4, 95% CI 0.8–7.2, p = 0.12). Conclusion: The presence of UMI was independently associated with an increased risk of cardiovascular events during long-term follow up. [ABSTRACT FROM AUTHOR]

Objective: SYNTAX score II (SSII) is a long-term mortality prediction model to guide the decision making of the heart-team between coronary artery bypass grafting or percutaneous coronary intervention (PCI) in patients with left main or three-vessel coronary artery disease. This study aims to investigate the long-term predictive value of SSII for all-cause mortality in patients with one- or two-vessel disease undergoing PCI. Methods: A total of 628 patients (76% men, mean age: 61±10 years) undergoing PCI due to stable angina pectoris (43%) or acute coronary syndrome (57%), included between January 2008 and June 2013, were eligible for the current study. SSII was calculated using the original SYNTAX score website (). Cox regression analysis was used to assess the association between continuous SSII and long-term all-cause mortality. The area under the receiver-operating characteristic curve was used to assess the performance of SSII. Results: SSII ranged from 6.6 to 58.2 (median: 20.4, interquartile range: 16.1–26.8). In multivariable analysis, SSII proved to be an independent significant predictor for 4.5-year mortality (hazard ratio per point increase: 1.10; 95% confidence interval: 1.07–1.13; p<0.001). In terms of discrimination, SSII had a concordance index of 0.77. Conclusion: In addition to its established value in patients with left main and three-vessel disease, SSII may also predict long-term mortality in PCI-treated patients with one- or two-vessel disease. [ABSTRACT FROM AUTHOR]

Objective: Studies have suggested a beneficial effect of angiotensin-converting enzyme (ACE) inhibition. To explore whether the ACE inhibitor ramipril has a direct effect on the microvasculature beyond the blood pressure (BP) lowering effect, we investigated whether ramipril improved coronary microvascular function in normotensive women with coronary microvascular dysfunction (CMD). Methods: We included 63 normotensive women with angina, no epicardial stenosis>50% and CMD defined as a coronary flow velocity reserve (CFVR)<2.2 assessed by adenosine stress-echocardiography in a randomized double-blinded, superiority trial with 1:1 allocation to placebo or ramipril (maximum dose 10 mg depending on blood pressure) for 24±6 weeks. Primary outcome was CFVR. Secondary outcomes were left ventricular systolic and diastolic function and symptoms evaluated by Seattle Angina Questionnaire (clinicaltrials.gov, NCT02525081). Results: Follow-up was available on 55 patients. BP remained unchanged during treatment in both groups. CFVR improved in both the ramipril (p = 0.004) and placebo group (p = 0.026) with no difference between groups (p = 0.63). Symptoms improved in both groups with no significant between-group differences. No changes were detected in parameters of systolic and diastolic function. No serious adverse reactions were reported. Conclusions: In normotensive women with angina and CMD, treatment with ramipril had no significant effect on CFVR or symptoms compared with placebo. The effect of ACE inhibition previously reported may be mediated by blood pressure reduction. [ABSTRACT FROM AUTHOR]

A prospective, multicenter study was initiated by the Government of Maharashtra, India, to determine predictors of long-term outcomes of percutaneous coronary intervention (PCI) for coronary artery disease, and to compare the effectiveness of drug-eluting stents (DESs) and bare-metal stents (BMSs) in patients undergoing PCI under government-funded insurance. The present analysis included 4595 patients managed between August 2012 and November 2016 at any of 110 participating centers. Using the classical multivariable regression and propensity-matching approach, we found age to be the most important predictor of 1-year mortality and target lesion revascularization at 1 year post-PCI. However, using machine learning methods to account for unmeasured confounders and bias in this large observational study, we determined total stent length and number of stents deployed as the most important predictors of 1-year survival, followed by age and employment status. The unadjusted death rates were 5.0% and 3.8% for the BMS and DES groups, respectively (p = 0.185, log-rank test). The rate of re-hospitalization (p<0.001) and recurrence of unstable angina (p = 0.08) was significantly lower for DESs than for BMSs. Increased use of DES after 2015 (following establishment of a price cap on DESs) was associated with a sharp decrease in adjusted hazard ratios of DESs versus BMSs (from 0.94 in 2013 to 0.58 in 2016), suggesting that high price was limiting DES use in some high-risk patients. Since stented length and stent number were the most important predictors of survival outcomes, adopting an ischemia-guided revascularization strategy is expected to help improve outcomes and reduce procedural costs. In the elderly, PCI should be reserved for cases where the benefits outweigh the higher risk of the procedure. As unemployed patients had poorer long-term outcomes, we expect that implementation of a post-PCI cardiovascular rehabilitation program may improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Our previous study examined an effect of remote ischemic preconditioning (RIPC) or intravenous nicorandil on reduction of periprocedural myocardial injury (pMI) following percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD). We further investigated the effect of RIPC or nicorandil on pMI in older patients. Methods: Patients with stable CAD who planned to undergo PCI were assigned to a 1:1:1 ratio to control, intravenous nicorandil, or upper-limb RIPC groups. This substudy analyzed patients aged >65 years (n = 282) from the principal cohort. The primary outcome was the incidence of pMI following PCI. We defined pMI as an elevated level of high-sensitive cardiac troponin T or creatine kinase myocardial band 12 or 24 hours after PCI. Results: We found that pMI following PCI was significantly reduced in the nicorandil group compared with the control group (37.2% vs. 53.7%, multiplicity-adjusted p = 0.046), but not in the RIPC group compared with the control group (43.0% vs. 53.7%, multiplicity-adjusted p = 0.245). The adjusted odds ratios (95% confidence interval) for pMI in the RIPC and nicorandil groups versus the control group were 0.63 (0.34 to 1.16) and 0.51 (0.27 to 0.96), respectively. Conclusion: Intravenous nicorandil significantly reduces pMI following PCI in a subgroup of older patients with stable CAD. Phase 3 trials are required to validate our results. Trial registration: UMIN Clinical Trials Registry . [ABSTRACT FROM AUTHOR]

Objective: To examine the prognosis of patients with cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome compared to patients without prior multimorbidity. Methods: This multicenter prospective cohort study in Switzerland included 5,635 patients hospitalized with acute coronary syndrome between 2009 and 2014, with a one-year follow-up period. We defined cardiovascular and non-cardiovascular multimorbidity as having at least two prior comorbidities before the index hospitalization. Multivariable adjusted Cox proportional models were built to assess the one-year risk of recurrent cardiovascular events, defined as cardiovascular mortality and non-fatal myocardial infarction or stroke. The final model was adjusted for age, gender, body mass index, tobacco consumption, education, and family history of cardiovascular disease, prescription of high-dose statinsat discharge and use of cardiac rehabilitation after discharge. Results: Overall, 3,664 patients (65%) had no multimorbidity, 1,839 (33%) had cardiovascular multimorbidity, 62 (1%) had non-cardiovascular multimorbidity, and 70 (1%) had both cardiovascular and non-cardiovascular multimorbidity. The multivariate risk of recurrent cardiovascular events was increased among patients with cardiovascular multimorbidity (hazard ratio (HR) 2.05, 95% CI: 1.54–2.73, p<0.001) and patients with non-cardiovascular multimorbidity (HR 2.57, 95% CI: 1.04–6.35, p = 0.04) compared to patients without multimorbidity. Patients with cardiovascular and non-cardiovascular multimorbidity had the highest risk of recurrence with a HR of 5.19, 95% CI: 2.79–9.64, p<0.001, compared to patients without multimorbidity. Conclusions: Multimorbidity increased by two-fold the risk of cardiovascular events over the year after an acute coronary syndrome. The magnitude of this increased risk was similar for patients with cardiovascular or non-cardiovascular multimorbidity. [ABSTRACT FROM AUTHOR]

Background: Coronary heart disease (CHD) mortality in England fell by 36% between 2000 and 2007 and it is estimated that approximately 50% of the fall was due to improved treatment uptake. Marked socio-economic inequalities in CHD mortality in the United Kingdom (UK) remain, with higher age-adjusted rates in more deprived groups. Inequalities in the persistence of medication for primary and secondary prevention of CHD may contribute to the observed social gradient and we investigated this possibility in the population of Wales (UK). Methods and findings: An electronic cohort of individuals aged over 20 (n = 1,199,342) in Wales (UK) was formed using linked data from primary and secondary care and followed for six years (2004–2010). We identified indications for medication (statins, aspirin, ACE inhibitors, clopidogrel) recommended in UK National Institute for Clinical Excellence (NICE) guidance for CHD (high risk, stable angina, stable angina plus diabetes, unstable angina, and myocardial infarction) and measured the persistence of indicated medication (time from initiation to discontinuation) across quintiles of the Welsh Index of Multiple Deprivation, an area-based measure of socio-economic inequality, using Cox regression frailty models. In models adjusted for demographic factors, CHD risk and comorbidities across 15 comparisons for persistence of the medications, none favoured the least deprived quintile, two favoured the most deprived quintile and 13 showed no significant differences. Conclusions: During our study period (2004–2010) we found no significant evidence of socio-economic inequality in the persistence of recommended medication for primary and secondary prevention of CHD. [ABSTRACT FROM AUTHOR]

Background: Evaluation of recurrent angina after percutaneous coronary interventions is challenging. Since bioresorbable vascular scaffolds (BVS) cause no artefacts in magnetic resonance imaging (MRI) due to their polylactate-based backbone, evaluation of vascular patency by MRI might allow for non-invasive assessment and triage of patients with suspected BVS failure. Methods: Patients with polylactate-based ABSORB-BVS in proximal coronary segments were examined with 3 Tesla MRI directly (baseline) and one year after implantation. For assessment of coronary patency, a high-resolution 3D spoiled gradient echo pulse sequence with fat-saturation, T2-preparation (TE: 40 ms), respiratory and end-diastolic cardiac gating, and a spatial resolution of (1.08 mm)3 was positioned parallel to the course of the vessel for bright blood imaging. In addition, a 3D navigator-gated T2-weighted variable flip angle turbo spin echo (TSE) sequence with dual-inversion recovery black-blood preparation and elliptical k-space coverage was applied with a voxel size of (1.14 mm)3. For quantitative evaluation lumen diameters of the scaffolded areas were measured in reformatted bright and black blood MR angiography data. Results: 11 patients with implantation of 16 BVS in the proximal coronary segments were included, of which none suffered from major adverse cardiac events during the one year follow up. Vascular patency in all segments implanted with BVS could be reliably assessed by MRI at baseline and after one year, whereas segments with metal stents could not be evaluated due to artefacts. Luminal diameter within the BVS remained constant during the one year period. One patient with atypical angina after BVS implantation was noninvasively evaluated showing a patent vessel, also confirmed by coronary angiography. Conclusions: Coronary MRI allows contrast-agent free and non-invasive assessment of vascular patency after ABSORB-BVS implantation. This approach might be supportive in the triage and improvement of diagnostic workflows in patients with postinterventional angina and scaffold implantation. Trial registration: German Register of Clinical Studies [ABSTRACT FROM AUTHOR]

Background: The different cardiovascular risk prediction scales currently available are not sufficiently sensitive. Aim: The aim of the present study was to analyze the contribution of the ankle-brachial index (ABI) added to the Framingham and REGICOR risk scales for the reclassification of cardiovascular risk after a 9-year follow up of a Mediterranean population with low cardiovascular risk. Design and setting: A population-based prospective cohort study was performed in the province of Barcelona, Spain. Method: A total of 3,786 subjects >49 years were recruited from 2006–2008. Baseline ABI was performed and cardiovascular risk was calculated with the Framingham and REGICOR scales. The participants were followed until November 2016 by telephone and review of the clinical history every 6 months to confirm the possible appearance of cardiovascular events. Results: 2,716 individuals participated in the study. There were 126 incidental cases of first coronary events (5%) during follow up. The incidence of coronary events in patients with ABI <0.9 was 4-fold greater than that of subjects with a normal ABI (17.2/1,000 persons-year versus 4.8/1,000 persons-year). Improvement in the predictive capacity of REGICOR scale was observed on including ABI in the model, obtaining a net reclassification improvement of 7% (95% confidence interval 0%-13%) for REGICOR+ ABI. Framingham + ABI obtained a NRI of 4% (-2%-11%). Conclusion: The results of the present study support the addition of the ABI as a tool to help in the reclassification of cardiovascular risk and to confirm the greater incidence of coronary events in patients with ABI < 0.9. [ABSTRACT FROM AUTHOR]

Background: The impact of high platelet reactivity (HPR) on clinical outcomes after elective percutaneous coronary interventions (PCI) with drug-eluting balloons (DEB) due to in-stent restenosis (ISR) is unknown. Objective: We sought to evaluate the prognostic importance of HPR together with conventional risk factors in patients treated with DEB. Methods: Patients treated with DEB due to ISR were enrolled in a single-centre, prospective registry between October 2009 and March 2015. Only patients with recent myocardial infarction (MI) received prasugrel, others were treated with clopidogrel. HPR was defined as an ADP-test >46U with the Multiplate assay and no adjustments were done based on results. The primary endpoint of the study was a composite of cardiovascular mortality, MI, any revascularization or stroke during one-year follow-up. Results: 194 stable angina patients were recruited of whom 90% were treated with clopidogrel. Clinical characteristics and procedural data were available for all patients; while platelet function testing was performed in 152 subjects of whom 32 (21%) had HPR. Patients with HPR had a higher risk for the primary endpoint (HR: 2.45; CI: 1.01–5.92; p = 0.03). The difference was primarily driven by a higher risk for revascularization and MI. According to the multivariate analysis, HPR remained a significant, independent predictor of the primary endpoint (HR: 2.88; CI: 1.02–8.14; p = 0.04), while total DEB length and statin treatment were other independent correlates of the primary outcome. Conclusion: HPR was found to be an independent predictor of repeat revascularization and MI among elective patients with ISR undergoing PCI with DEB. [ABSTRACT FROM AUTHOR]

Background: Although depression is common in patients with heart disease, screening for depression is much debated. DEPSCREEN-INFO showed that a patient-targeted feedback in addition to screening results in lower depression level six months after screening. The purpose of this analysis was to perform a cost-effectiveness analysis of DEPSCREEN-INFO. Methods: Patients with coronary heart disease or arterial hypertension were included. Participants in both groups were screened for depression. Participants in the intervention group additionally received a patient-targeted feedback of their result and recommended treatment options. A cost-utility analysis using quality-adjusted life years (QALY) based on the EQ-5D was performed. The time horizon was 6 months. Resource utilization was assessed by a telephone interview. Multiple imputation using chained equations was used. Net-benefit regressions controlled for prognostic variables at baseline were performed to construct cost-effectiveness acceptability curves. Different sensitivity analyses were performed. Results: 375 participants (intervention group: 155; control group: 220) were included at baseline. After 6 months, in the intervention group adjusted total costs were lower (-€2,098; SE: €1,717) and more QALY were gained (0.0067; SD: 0.0133); yet differences were not statistically significant. The probability of cost-effectiveness was around 80% independent of the willingness-to-pay (range: €0/QALY–€130,000/QALY). The results were robust. Conclusions: A patient-targeted feedback in addition to depression screening in cardiology is cost-effective with a high probability. This underpins the use of the patient-targeted feedbacks and the PHQ-9 that are both freely available and easy to implement in routine care. [ABSTRACT FROM AUTHOR]

We aimed to assess the clinical significance of serum levels of neutrophil gelatinase-associated lipocalin (sNGAL) for predicting in-hospital outcomes in patients with ST-elevated myocardial infarction (STEMI). Patients admitted within 24 hours of developing STEMI clinical symptoms were evaluated for sNGAL on hospitalization days 1 and 12. Recurrent myocardial infarction, early post-infarction angina, acute cerebrovascular accident, and death were assessed as adverse outcomes during hospitalization. The actors associated with adverse outcome were evaluated using univariate and multivariate regression analysis. Among the 260 STEMI patients included, 32% had ≥1 adverse in-hospital outcome, and significantly higher sNGAL on day 12, (but not on day 1) compared to sNGAL in patients with favorable outcome (p = 0.033). Type-2 diabetes mellitus, age > 60 years, reduced glomerular filtration rate during hospitalization, and high sNGAL on day 12 were identified as risk factors for adverse in-hospital outcome, associated with a 14% increase for each 1-year increment in age after 60 years, and a dramatic increase (3.2 times) for high sNGAL on day 12, with sNGAL ≥ 1.046 ng/ml indicating complicated hospitalization course. sNGAL concentration on the 12th day was associated with the existing adverse outcomes, acting as a marker of MI severity. [ABSTRACT FROM AUTHOR]

Background: Arterial access and hemostasis are important processes during percutaneous coronary procedures. In this study, we tested if the use of chitosan-based pads on top of compression devices could improve hemostasis efficacy compared with compression devices alone after transradial coronary angiography or interventions. Methods: This study was a single-center open-label randomized controlled trial. Patients who underwent coronary angiography or intervention with the transradial approach were randomly assigned to the study (compression device and a chitosan-based pad) or control (compression devices alone) group in a 2:1 fashion. The primary endpoint was time to hemostasis, categorized into ≤5, 6–10, 11–20, and >20 minutes. Results: Between April and July 2016, 95 patients were enrolled (59 were assigned to the study arm and 36 to the control arm). Time to hemostasis, the primary endpoint, was significantly lower in the study group than in the control group (p<0.001). Both groups showed low rates of vascular complications. Conclusions: This study suggests that the use of a hemostasis pad in combination with rotatory compression devices is a safe and effective hemostasis strategy after radial artery access. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Objectives: To calculate the prevalence of all falls, non-accidental falls and syncope in an older population and characterize cardiovascular risk profiles. Design: Prospective, longitudinal cohort study. Setting: The first two waves of data from the Irish Longitudinal Study on Ageing (TILDA). Participants: 8172 community-dwelling adults aged 50 years and older resident in the Republic of Ireland Measurements: Self-reported history of all falls, non-accidental falls and syncope in the year preceding the first two waves of data collection. Demographic factors and self-reported cardiovascular conditions were used to characterize cardiovascular risk profiles. Results: The prevalence of all falls in the past year was 19.2% or 192 per thousand persons and increased with age (50–64 years 17.5%; 65–74 years 19.4%; 75+ years 24.4%). Non-accidental falls had an estimated prevalence of 5.1% or 51 falls per thousand persons and accounted for 26.5% of all falls reported and also increased with age (50–64 years 4.0%; 65–74 years 5.5%; 75+ years 8.0%). The prevalence for syncope was estimated to be 4.4% or 44per thousand persons but did not show a similar age gradient. Participants with at least 5 cardiovascular conditions were more likely to report all falls (OR = 2.07, 95% CI 1.18–3.64, p<0.05) and NAF (OR = 2.89, 95%CI 1.28–6.52, p<0.05). Conclusions: The prevalence of all falls and non-accidental falls increases with age but the same pattern was not consistently observed for syncope. There is an increased odds of reporting all three outcomes with increasing number of self-reported cardiovascular conditions. Further work is needed to uncover the interplay between cardiovascular disease and subsequent falls. [ABSTRACT FROM AUTHOR]

Background: Circulating endothelial cells (CECs) are widely reported as a promising biomarker of endothelial damage/dysfunction in coronary artery disease (CAD). The two popular methods of CEC quantification include the use of immunomagnetic beads separation (IB) and flow cytometry analysis (FC); however, they suffer from two main shortcomings that affect their diagnostic and prognostic responses: non-specific bindings of magnetic beads to non-target cells and a high degree of variability in rare cell identification, respectively. We designed a microfluidic chip with spatially staggered micropillars for the efficient harvesting of CECs with intact cellular morphology in an attempt to revisit the diagnostic goal of CEC counts in CAD patients with angina pectoris. Methods: A label-free microfluidic assay that involved an in-situ enumeration and immunofluorescent identification (DAPI+/CD146+/VEGFR1+/CD45-) of CECs was carried out to assess the CEC count in human peripheral blood samples. A total of 55 CAD patients with angina pectoris [16 with chronic stable angina (CSA) and 39 with unstable angina (UA)], together with 15 heathy controls (HCs) were enrolled in the study. Results: CEC counts are significantly higher in both CSA and UA groups compared to the HC group [respective medians of 6.9, 10.0 and 1.5 cells/ml (p < 0.01)]. Further, a significant elevation of CEC count was observed in the three UA subgroups [low risk (5.3) vs. intermediate risk (10.8) vs. high risk (18.0) cells/ml, p < 0.001) classified in accordance to the TIMI NSTEMI/UA risk score system. From the receiver-operating characteristic curve analysis, the AUCs for distinguishing CSA and UA from HC were 0.867 and 0.938, respectively. The corresponding sensitivities were 87.5% and 84.6% and the specificities were 66.7% and 86.7%, respectively. Conclusions: Our microfluidic assay system is efficient and stable for CEC capture and enumeration. The results showed that the CEC count has the potential to be a promising clinical biomarker for the assessment of endothelial damage/dysfunction in CAD patients with angina pectoris. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) is associated with high morbidity and mortality, particularly in the first 12 months post-event. Interventions such as dual antiplatelet therapy can reduce the risk of major adverse cardiovascular events (MACE), but the duration of the high-risk time interval and the optimal prescription time frame for these interventions remains unknown. Design, setting, participants, and measurements: We performed a retrospective cohort study using data from medical services and hospitalizations in Manitoba, Canada for patients admitted with a MI between April 2006 and March 2010, and followed until Nov 30, 2014. We used survival analysis to determine the cumulative incidence of death, subsequent MI, or stroke, and used Cox proportional hazards models to assess factors associated with these endpoints. Results: There were 8,493 patients in Manitoba admitted to hospital for a MI during the study period. Of those, 6,749 (79.5%) survived for at least 1 year without a recurrent MI or stroke. In the following year, this population remained at high risk, with 372 (5.5%) of the remaining patients dying in the next twelve months (48.1% cardiovascular deaths), 244 (3.6%) having a recurrent MI, and 74 (1.1%) having a stroke. Older age, male sex, diabetes, prior stroke, prior heart failure, prior unstable angina, and absence of revascularization were associated with worse long-term prognosis. Conclusions: The risk of MACE remains elevated among post-MI patients after the first year. Interventions to more intensively monitor, evaluate, and treat these patients should be considered beyond the first year following myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: The involvement of cholesterol crystals (CCs) in plaque progression and destabilization of atherosclerotic plaques has been recently recognized. This study aimed to evaluate the association between the intraplaque localization of CCs and plaque vulnerability. Methods: We investigated 55 acute coronary syndrome (ACS) and 80 stable angina pectoris (stable AP) lesions using optical frequency domain imaging (OFDI) prior to percutaneous coronary intervention. The distance between CCs and the luminal surface of coronary plaques was defined as CC depth. Results: Although the incidence of CCs had similar frequencies in the ACS and stable AP groups (95% vs. 89%, p = 0.25), CC depth was significantly less in patients with ACS than in those with stable AP (median [25th to 75th percentile]: 68 μm [58 to 92 μm] vs. 152 μm [115 to 218 μm]; p < 0.001). The incidences of plaque rupture, thrombus, lipid-rich plaques, and thin-cap fibroatheroma were significantly greater in patients with ACS than in those with stable AP (62% vs. 18%, p < 0.001; 67% vs. 16%, p < 0.001; 84% vs. 57%, p < 0.01; and 56% vs. 19%, p < 0.001, respectively). Conclusion: OFDI analysis revealed that CCs were found in the more superficial layers within the coronary atherosclerotic plaques in patients with ACS than in those with stable AP, suggesting that CC depth is associated with plaque vulnerability. CC depth, a novel OFDI-derived parameter, could be potentially used as an alternative means of evaluating plaque vulnerability in coronary arteries. [ABSTRACT FROM AUTHOR]

Background: Nocturnal leg cramps (NLC) are common and poorly understood. Objective: To determine the prevalence of NLC and associations with cardiometabolic, sleep, and behavioral risk factors in the US population. Design: Cross-sectional epidemiology. Participants: National Health and Nutrition Examination Survey, 2005–2006 and 2007–2008 waves. Main outcome(s) and measure(s): NLC were assessed with, “In the past month, how often did you have leg cramps while trying to sleep?” Responses were categorized as None, Mild, or Moderate-Severe. Demographics, medical history, sleep disturbances, and cardiometabolic risk factors were evaluated using the 2005–2006 dataset. Variables that demonstrated significant relationships to NLC after adjusting for age, sex, education, and BMI were assessed in the 2007–2008 dataset. Variables that were still significant were entered into a forward stepwise regression model combining both waves, to determine which variables best explained the variance in NLC. Results: Prevalence was 24–25% reporting mild and 6% reporting moderate-severe NLC. NLC increased with age, lower education, unemployment, shorter sleep duration, all assessed sleep symptoms (nocturnal "leg jerks", snoring, snorting/gasping, difficulty falling asleep, difficulty maintaining sleep, non-restorative sleep, sleepiness, use of sleep medications), higher BMI, smoking, medical history (hypertension, heart failure, angina, stroke, arthritis, respiratory disease, and cancer), depression symptoms, and biomarkers (CRP, HbA1c, calcium, cadmium, red blood cells). Stepwise analysis showed that moderate-severe nocturnal leg cramps were associated with (in decreasing order of partial R2): leg jerks, poor overall health, arthritis, difficulty falling asleep, age, nonrestorative sleep, red blood cell count, lower education, angina, and difficulty maintaining sleep. Conclusions and relevance: Based on this first large, representative study, NLC occurring >5x per month are reported by 6% of the adult US population. Sleep disturbance symptoms and health conditions are associated with higher frequency of NLC, suggesting that NLC is a marker, and possibly contributor, to poor sleep and general health. [ABSTRACT FROM AUTHOR]

Background: Clinical and echocardiography follow-up is recommended in patients with aortic stenosis to detect symptom onset, thus a watchful waiting approach has to be safe and effective. For both AS patients and their general practitioners, evaluation of valvular heart disease (VHD) knowledge, after the indexed specialized assessment has never been measured. Aims: To evaluate the knowledge of clinical symptoms of aortic stenosis by both patients and their general practitioner. Methods: Sixty-four patients, with moderate to severe and initially asymptomatic AS (median AVA (interquartile range) 1.01(0.80–1.15) cm2) previously referred to a tertiary center and medically managed for at least 6 months after the index echocardiogram, and their primary care doctors were interviewed on the phone and asked to answer specific questions related to knowledge of aortic stenosis symptoms. Results: Fifty-six percent of patients quoted shortness of breath as one of the aortic stenosis symptoms, and only 16% knew the 3 aortic stenosis symptoms. Fifty percent of patients reported having received sufficient information regarding aortic stenosis; only 48% remembered receiving information regarding specific symptoms. Only 14% general practitioners quoted the 3 specific symptoms. According to the initial recommendation, only 41 patients (64%) benefitted from a 6-to-12 month clinical and echocardiography follow up. Conclusion: GPs are not sufficiently trained to safely manage AS patients in the community and to ensure adequate follow-up and monitoring. AS patients were not properly informed about their diagnosis and symptomatology. Hence, therapeutic education should be improved for patients with asymptomatic AS and continuous medical education on VHD should be reinforced, for GPs. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to test the hypothesis suggesting that the pre-intervention levels of proinflammatory cytokines, anti-inflammatory cytokines, and angiogenic growth factors predict the long-term clinical results of autologous bone marrow-derived mononuclear cell (ABMMC) transplantation in patients with primary ST elevation myocardial infarction (STEMI). Methods and results: From 2003 to 2006, a total of 62 patients with primary STEMI were enrolled in an open randomized study registered under the title ESTABOMA. Patients were randomized into two groups: group 1 included patients treated with percutaneous coronary intervention (PCI) and ABMMC transplantation (n = 28); group 2 comprised patients treated only with PCI (n = 34). Follow-up study was performed 7.96 ± 0.96 years after STEMI and involved physical examination, six-minute walk test, echocardiography, and determination of brain natriuretic peptide (BNP) levels. The total and cardiovascular mortality rates were higher in group 1 compared with group 2: 36% (n = 10) vs. 12% (n = 4) (p = 0.02) and 29% (n = 8) vs. 6% (n = 2) (p = 0.03), respectively. Lower levels of proinflammatory cytokines were observed in group 1 after PCI and ABMMC transplantation. Serum levels of FGF, VEGF, and IL-10, determined before PCI and ABMMC transplantation were prognostically significant long-term indicators of unfavorable course of CAD after STEMI. [ABSTRACT FROM AUTHOR]

Aims: The diagnosis of stable angina involves the use of probability estimates based on clinical presentation, age, gender and cardiovascular risk factors. In view of the link between the cardiac and systemic vasculature we tested whether non-invasive measures of systemic micro- and macrovascular structure and function differentiate between individuals with flow-limiting coronary artery disease (CAD) and those with normal coronary arteries (NCA). Methods and results: We recruited 84 patients undergoing elective coronary angiography for investigation of symptoms of stable angina. Patients were selected for either having significant CAD or NCA (n = 43/41; age, 56±7 vs 57±7 years, P = 0.309). Only microvascular endothelial function, measured using the Endo-PAT2000 device to determine reactive hyperaemia index (CAD vs. NCA; 1.9 [1.5; 2.3] vs. 2.1 [1.8; 2.4], P = 0.03) and sonographic carotid plaque score (CAD vs. NCA; 3.0 [1.5; 4.5] vs. 1.2 [0; 2.55], P<0.001) were significantly different between patients with CAD and NCA. No significant differences were detected in reflection magnitude (CAD vs. NCA; 1.7 [1.5; 1.8] % vs 1.7 [1.5; 1.9] %, P = 0.342), pulse wave velocity (CAD vs. NCA; 7.8±1.4 m/sec vs. 8.3±1.5 m/sec, P = 0.186), carotid intima-media thickness (CAD vs. NCA; 0.73±0.10 mm vs. 0.75±0.10 mm, P = 0.518) or carotid distensibility (CAD vs. NCA; 3.8±1.2 10-3/kPa vs. 3.4±0.9 10-3/kPa, P = 0.092). Also, the c-statistic of the pre-test probability based on history and traditional risk factors (c = 0.665; 95% CI, 0.540–0.789) was improved by the addition of the inverse RHI (c = 0.720; 95% CI, 0.605–0.836), carotid plaque score (c = 0.770, 95% CI, 0.659–0.881), and of both markers in combination (c = 0.801; 95% CI, 0.701–0.900). Conclusion: There are distinct differences in the systemic vasculature between patients with CAD and NCA that may have the potential to guide diagnostic and therapeutic decisions. Carotid artery plaque burden and microvascular function appear to be most promising in this context. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is the main cause of death in Austria. However, no systematic information exists regarding characteristics and treatments of contemporary patients with stable coronary artery disease (CAD) in Austria. We assembled two retrospective physicians’ databases to describe demographics, clinical profiles, and therapeutic strategies in patients with stable CAD. In addition, we compared patient profiles of secondary care internists and hospital-based cardiologists with those of general practitioners in a primary care setting outside of hospital. Methods: The study population was identified from retrospective chart review of 1020 patients from 106 primary care physicians in Austria (ProCor II registry), and was merged with a previous similar database of 1280 patients under secondary care (ProCor I registry) to yield a total patient number of 2300. Results: Female patients with stable CAD were older, had more angina and/or heart failure symptoms, and more depression than males. Female gender, type 2 diabetes mellitus, higher CCS class and asthma/COPD were predictors of elevated heart rate, while previous coronary events/revascularization predicted a lower heart rate in multivariate analysis. There were no significant differences with regard to characteristics and management of patients of general practitioners in the primary care setting versus internists in secondary care. Conclusions: Characteristics and treatments of unselected patients with stable ischemic heart disease in Austria resemble the pattern of large international registries of stable ischemic heart disease, with the exception that diabetes and systemic hypertension were more prevalent. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010–2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17–2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24–3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05–3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05–2.77), depression (OR 2.38, 95% CI 1.47–3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15–4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment. [ABSTRACT FROM AUTHOR]

Background: Despite substantial falls in coronary heart disease (CHD) mortality in the United Kingdom (UK), marked socioeconomic inequalities in CHD risk factors and CHD mortality persist. We investigated whether inequity in CHD healthcare in Wales (UK) could contribute to the observed social gradient in CHD mortality. Methods and findings: Linking data from primary and secondary care we constructed an electronic cohort of individuals (n = 1199342) with six year follow-up, 2004–2010. We identified indications for recommended CHD interventions, measured time to their delivery, and estimated risk of receiving the interventions for each of five ordered deprivation groups using a time-to-event approach with Cox regression frailty models. Interventions in primary and secondary prevention included risk-factor measurement, smoking management, statins and antihypertensive therapy, and in established CHD included medication and revascularization. For primary prevention, five of the 11 models favoured the more deprived and one favoured the less deprived. For medication in secondary prevention and established CHD, one of the 15 models favoured the more deprived and one the less deprived. In relation to revascularization, six of the 12 models favoured the less deprived and none favoured the more deprived–this evidence of inequity exemplified by a hazard ratio for revascularization in stable angina of 0.79 (95% confidence interval 0.68, 0.92). The main study limitation is the possibility of under-ascertainment or misclassification of clinical indications and treatment from variability in coding. Conclusions: Primary care components of CHD healthcare were equitably delivered. Evidence of inequity was found for revascularization procedures, although this inequity is likely to have only a modest effect on social gradients in CHD mortality. Policymakers should focus on reducing inequalities in CHD risk factors, particularly smoking, as these, rather than inequity in healthcare, are likely to be key drivers of inequalities in CHD mortality. [ABSTRACT FROM AUTHOR]

Background: Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors. Methods and findings: We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status, and deprivation. Secondly, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2·64 [95% CI 2·34–2·97]); those with angina were four times more likely to have chronic pain (OR 4·19 [3·64–4·82]); those with depression were twice as likely to have angina (OR 2·20 [1·90–2·54]). Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05–1·71]), angina predicted chronic pain in the other (OR 2·19 [1·63–2·95]), and depression, angina (OR 1·98 [1·49–2·65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99–4·78]); angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05–9·95]) and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85–12·98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01). Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06–0·23]). Conclusion: We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort) suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms. [ABSTRACT FROM AUTHOR]

Background: Anxiety and cardiac autonomic modulations (CAM) were thoroughly investigated in coronary artery disease (CAD) and cardiac syndrome X (CSX) patients worldwide, but not among Sudanese with similar pathology. Aims: To compare levels of anxiety and CAM between Sudanese patients with CSX and CAD. Materials and Methods: Anxiety was evaluated in 51 CAD and 26 CSX patients using Taylor Manifest anxiety score (TMAS) questionnaire while heart rate variability derived indices were used to assess CAM, namely natural logarithm of low frequency (LnLF), high frequency (LnHF) and LF/HF ratio (LnLF/HF). Results: Low anxiety levels were achieved by 6 (23.1%) and 9 (17.6%) patients with CSX and CAD respectively. High anxiety level was achieved by only one (3.8%) patient, who was suffering from CSX. TMAS was significantly higher in CSX (31.27 (21.97)) compared to CAD (21.86 (12.97), P = 0.021). However, abnormally increased anxiety was not associated with higher risk of CSX. LnLF, LnHF and LnLF/HF were comparable in CAD and CSX patients. Conclusion: CSX and CAD patients showed comparable CAM. Although anxiety levels were higher in CSX compared to CAD, TMAS ≥ 35 failed to show significant association with CSX. [ABSTRACT FROM AUTHOR]

Background: Pulse-wave velocity (PWV) measures aortic stiffness. It is an independent predictor of cardiovascular events and mortality, yet there is paucity in the literature on its association with the severity and extent of coronary artery disease (CAD). Methods: To examine the utility of PWV in predicting CAD burden in men and women the PWV was determined in 344 patients (Men = 266, Women = 78) presenting for invasive coronary angiography for the assessment of suspected CAD. Pearson correlations and multivariate analysis were used to evaluate the relationship between these coronary scores, PWV and traditional cardiovascular risk factors. Results: Compared to men, women with chest pain had lower mean Extent scores (19.2 vs. 35.6; p = 0.0001) and Gensini scores (23.6 vs. 41.9; p = 0.0001). PWV was similar between men and women (12.35 ± 3.74 vs. 12.43 ± 4.58; p = 0.88) and correlated with Extent score (r = 0.21, p = 0.0001) but not Gensini or vessel score (r = 0.03, p = 0.64 and r = 0.06, p = 0.26, respectively). PWV was associated with Extent score in men (B = 2.25 ± 0.78, p = 0.004 for men and B = 1.50 ± 0.88, p = 0.09 for women). It was not a predictor of Gensini score (B = -0.10, P = 0.90). Conclusion: PWV correlates with the extent of CAD, as measured by the ‘Extent’ score in men more than women. However, it does not correlate with the severity of obstructive CAD in either gender. [ABSTRACT FROM AUTHOR]

Objective: The risk for cardiovascular disease (CVD) is higher for individuals with a first-degree relative who developed premature CVD (with a threshold at age 55 years for a male or 65 years for a female). However, little is known about the effect that each unit increase or decrease of maternal or paternal age of onset of CVD has on offspring age of onset of CVD. We hypothesized that there is an association between maternal and paternal age of onset of CVD and offspring age of onset of CVD. Methods: We used the Framingham Heart Study database and performed conditional imputation for CVD-censored parental age (i.e. parents that didn’t experience onset of CVD) and Cox proportional regression analysis, with offspring’s age of onset of CVD as the dependent variable and parental age of onset of CVD as the primary predictor. Modifiable risk factors in offspring, such as cigarette smoking, body mass index (BMI), diabetes mellitus, systolic blood pressure (SBP), high-density lipoprotein (HDL) level, and low-density lipoprotein (LDL) level, were controlled for. Separate analyses were performed for the association between maternal age of onset of CVD and offspring age of onset of CVD and the association between paternal age of onset of CVD and offspring age of onset of CVD. Results: Parental age of onset of CVD was predictive of offspring age of onset of CVD for maternal age of onset of CVD (P < .0001; N = 1401) and for paternal age of onset of CVD (P = 0.0134; N = 1221). A negative estimate of the coefficient of interest signifies that late onset of cardiovascular events in parents is protective of onset of CVD in offspring. Cigarette smoking and HDL level were important associated confounders. Conclusions: Offspring age of onset of cardiovascular disease is significantly associated with both maternal and paternal age of onset CVD. The incorporation of the parameters, maternal or paternal age of onset of CVD, into risk estimate calculators may improve accuracy of identification of high-risk patients in clinical settings. [ABSTRACT FROM AUTHOR]

Background and objective: Henoch-Schönlein purpura (HSP) is an important cause of chronic kidney disease in children. This meta-analysis identified risk factors associated with renal involvement in childhood HSP. Methods: PubMed, Embase, and Web of Science were searched. The quality of all eligible studies was assessed using the Newcastle-Ottawa scale criteria. An analysis of possible risk factors was conducted to report the odds ratio (OR) and weighted mean difference (WMD). Results: Thirteen studies (2398 children) revealed 20 possible and 13 significant risk factors associated with renal involvement in HSP, with the following meta-analysis estimates of OR and WMD, with 95% confidence intervals: older age (0.90, 0.61–1.19); age > 10 y (3.13, 1.39–7.07); male gender (1.36, 1.07–1.74); abdominal pain (1.94,1.24–3.04); gastrointestinal bleeding (1.86, 1.30–2.65); severe bowel angina (3.38, 1.17–9.80); persistent purpura (4.02, 1.22–13.25); relapse (4.70, 2.42–9.14); WBC > 15 × 109/L (2.42, 1.39–4.22); platelets > 500 × 109/L (2.98, 1.22–7.25); elevated antistreptolysin O (ASO) (2.17, 1.29–3.64); and decreased complement component 3 (C3) (3.13, 1.62–6.05). Factors not significantly associated with renal involvement were: blood pressure; orchitis; elevated C-reactive protein; elevated erythrocyte sedimentation rate (ESR); and elevated serum IgA/IgE or IgG. Arthritis/arthralgia may be a risk factor according to the criteria of the American College of Rheumatology (1.41, 1.01–1.96). Conclusion: The following are associated with renal involvement in pediatric HSP: male gender; > 10 y old; severe gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding, and severe bowel angina); arthritis/arthralgia; persistent purpura or relapse; WBC > 15 × 109/L; platelets > 500 × 109/L; elevated ASO; and low C3. Relevant clinical interventions for these risk factors may exert positive effects on the prevention of kidney disease during the early stages of HSP. However, the results should be interpreted cautiously due to the limitations of the studies. [ABSTRACT FROM AUTHOR]

Objective: To identify adherence patterns over time and their predictors for evidence-based medications used after hospitalization for coronary heart disease (CHD). Patients and Methods: We built a population-based retrospective cohort of all patients discharged after hospitalization for CHD from public hospitals in the Valencia region (Spain) during 2008 (n = 7462). From this initial cohort, we created 4 subcohorts with at least one prescription (filled or not) from each therapeutic group (antiplatelet, beta-blockers, ACEI/ARB, statins) within the first 3 months after discharge. Monthly adherence was defined as having ≥24 days covered out of 30, leading to a repeated binary outcome measure. We assessed the membership to trajectory groups of adherence using group-based trajectory models. We also analyzed predictors of the different adherence patterns using multinomial logistic regression. Results: We identified a maximum of 5 different adherence patterns: 1) Nearly-always adherent patients; 2) An early gap in adherence with a later recovery; 3) Brief gaps in medication use or occasional users; 4) A slow decline in adherence; and 5) A fast decline. These patterns represented variable proportions of patients, the descending trajectories being more frequent for the beta-blocker and ACEI/ARB cohorts (16% and 17%, respectively) than the antiplatelet and statin cohorts (10% and 8%, respectively). Predictors of poor or intermediate adherence patterns were having a main diagnosis of unstable angina or other forms of CHD vs. AMI in the index hospitalization, being born outside Spain, requiring copayment or being older. Conclusion: Distinct adherence patterns over time and their predictors were identified. This may be a useful approach for targeting improvement interventions in patients with poor adherence patterns. [ABSTRACT FROM AUTHOR]

We aimed to determine the levels of microRNAs (miRNAs) in sera and HDL of acute coronary syndrome (ACS) compared to stable angina (SA) patients with/without hyperglycemia, and evaluate comparatively the functional effect of these sera on the processing machinery proteins (Drosha, DGCR8, Dicer) and miRNAs production in human macrophages. MiRNAs levels in sera and HDL from 35 SA and 72 ACS patients and 30 healthy subjects were measured by using microRNA TaqMan assays. MiR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a levels were higher in the hyperglycemic ACS compared to normoglycemic sera. MiR-223 and miR-486 prevailed in HDL2, while miR-92a predominated in HDL3, all three miRNAs discriminating between ACS and SA patients; their levels were increased in HDL from hyperglycemic ACS patients versus normoglycemic ones. The incubation of human macrophages with sera from ACS and SA patients showed that all patients’ sera induced an increase of Drosha, DGCR8 and Dicer expressions and of selected miRNAs levels compared to control sera, the effect being higher in the case of hyperglycemic versus normoglycemic ACS sera. The addition of glucose to SA and ACS sera increased Drosha, DGCR8 and Dicer expression and miRNAs levels in the exposed macrophages. In conclusion, hyperglycemia is associated with increased miR-223, miR-92a, miR-486 levels in HDL, which discriminate between ACS and SA patients. Exposure of human macrophages to ACS compared to SA sera determines the upregulation of Drosha, DGCR8 and Dicer expression and the increase of selected miRNAs production, the effect being augmented by an increased glucose concentration. [ABSTRACT FROM AUTHOR]

A previous genome-wide association study showed that a single nucleotide polymorphism (SNP) rs2107595 in histone deacetylase 9 (HDAC9) gene was associated with large artery stroke (LAS) in Caucasians. Based on the similar atherosclerotic pathogenesis between LAS and coronary artery disease (CAD), we aimed to evaluate the associations of SNP rs2107595 with CAD risk and the severity of coronary atherosclerosis in a Chinese Han population, and explore the potential gene-environment interactions among SNP rs2107595 and conventional CAD risk factors. In a two-stage case-control study with a total of 2317 CAD patients and 2404 controls, the AG + AA genotypes of SNP rs2107595 were significantly associated with increased CAD risk (Adjusted odds ratio (OR) = 1.23, Padj = 0.001) and higher modified Gensini scores (Adjusted OR = 1.38, Padj < 0.001). These associations remained significant in subtype analyses for unstable angina pectoris (UAP), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Subgroup and multifactor dimensionality reduction analyses (MDR) further found the gene-environment interactions among SNP rs2107595, body mass index, type 2 diabetes and hyperlipidemia in CAD risk and the severity of coronary atherosclerosis. Moreover, patients with CAD had higher levels of HDAC9 mRNA expression and plasma HDAC9 than controls. Subsequent genotype-phenotype analyses observed the significant correlations of SNP rs2107595 with HDAC9 mRNA expression and plasma HDAC9 levels in controls and patients with NSTEMI and STEMI. Taken together, our data suggest that SNP rs2107595 may contribute to coronary atherosclerosis and CAD risk through a possible mechanism of regulating HDAC9 expression and gene-environment interactions. [ABSTRACT FROM AUTHOR]

Background: Stroke is a rare but serious adverse event associated with percutaneous coronary intervention (PCI). However, the relative risk of stroke between stable patients undergoing a direct PCI strategy and those undergoing an initial optimal medical therapy (OMT) strategy has not been established yet. This study sought to investigate if, in patients with stable coronary artery disease (SCAD), an initial strategy PCI is associated with a higher risk of stroke than a strategy based on OMT alone. Methods: We performed a meta-analysis of 6 contemporary randomized control trials in which 5673 patients with SCAD were randomized to initial PCI or OMT. Only trials with stent utilization more than 50% were included. Study endpoint was the rate of stroke during follow up. Results: Mean age of patients ranged from 60 to 65 years and stent utilization ranged from 72% to 100%. Rate of stroke was 2.0% at a weighted mean follow up of 55.3 months. On pooled analysis, the risk of stroke was similar between patients undergoing a PCI plus OMT and those receiving only OMT (2.2% vs. 1.8%, OR on fixed effect = 1.24 95%CI: 0.85–1.79). There was no heterogeneity among the studies (I2 = 0.0%, P = 0.15). On sensitivity analysis after removing each individual study the pooled effect estimate remains unchanged. Conclusions: In patients with SCAD an initial strategy based on a direct PCI is not associated with an increased risk of stroke during long-term follow up compared to an initial strategy based on OMT alone. [ABSTRACT FROM AUTHOR]

Objectives: Dental infections, such as periodontitis, associate with atherosclerosis and its complications. We studied a cohort followed-up since 1985 for incidence of angina pectoris with the hypothesis that calculus accumulation, proxy for poor oral hygiene, links to this symptom. Methods: In our Swedish prospective cohort study of 1676 randomly selected subjects followed-up for 26 years. In 1985 all subjects underwent clinical oral examination and answered a questionnaire assessing background variables such as socio-economic status and pack-years of smoking. By using data from the Center of Epidemiology, Swedish National Board of Health and Welfare, Sweden we analyzed the association of oral health parameters with the prevalence of in-hospital verified angina pectoris classified according to the WHO International Classification of Diseases, using descriptive statistics and logistic regression analysis. Results: Of the 1676 subjects, 51 (28 women/23 men) had been diagnosed with angina pectoris at a mean age of 59.8 ± 2.9 years. No difference was observed in age and gender between patients with angina pectoris and subjects without. Neither was there any difference in education level and smoking habits (in pack years), Gingival index and Plaque index between the groups. Angina pectoris patients had significantly more often their first maxillary molar tooth extracted (d. 16) than the other subjects (p = 0.02). Patients also showed significantly higher dental calculus index values than the subjects without angina pectoris (p = 0.01). Multiple regression analysis showed odds ratio 2.21 (95% confidence interval 1.17–4.17) in the association between high calculus index and angina pectoris (p = 0.015). Conclusion: Our study hypothesis was confirmed by showing for the first time that high dental calculus score indeed associated with the incidence of angina pectoris in this cohort study. [ABSTRACT FROM AUTHOR]