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The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations. SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score ≥33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972. SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (pinteraction 0·0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (pinteraction 0·67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0·725 and for external (DELTA registry) validation of 0·716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0·567 and 0·612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI. Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score. Boston Scientific Corporation.

ObjectiveTo evaluate the long-term follow-up of the unrestricted use of a biodegradable polymer-coated drug-eluting stent in patients undergoing percutaneous coronary intervention (PCI).MethodsThe Nobori 2 study was a prospective, multicentre, observational registry evaluating the safety and the efficacy of the biodegradable polymer biolimus-eluting stent (BP-BES) among 3067 patients recruited at 125 international sites. The primary combined endpoint was a composite of cardiac death, myocardial infarction and target-lesion revascularisation (TLR).ResultsFive-year follow-up was available in 2738 (89.3%) patients. The combined endpoint occurred in 268 patients (10%, 95% CIs 8.9% to 11.3%) at 5 years, with 3.9% of events during the first year and 6.2% during years 1–5 of follow-up. Cumulative rates of TLR and definite/probable stent thrombosis were 5.3% (95% CI 4.5% to 6.3%) and 1.1% (95% CI 0.8% to 1.6%), respectively. Between 1 and 5 years, TLR and very late stent thrombosis rates were 3.5% (95% CI 2.8% to 4.4%) and 0.6% (95% CI 0.3% to 1.1%), respectively. Previous PCI (HR, 2.05, 95% CI 1.68 to 2.50), moderate-to-severe renal disease (HR, 1.89, 95% CI 1.30 to 2.74) and peripheral vascular disease (HR, 1.86, 95% CI 1.38 to 2.52) were the three most powerful independent predictors of the combined endpoint at 5 years.ConclusionsThe final 5-year follow-up of the Nobori 2 registry demonstrates the safety and effectiveness of the BP-BES in an unselected, broadly inclusive cohort of PCI patients, highlighting the excellent performance of this coronary stent technology after polymer biodegradation.Trial registration numberISRCTN81649913; Results.

Aims/hypothesisFew studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes.MethodsData were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593).ResultsData from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001).Conclusions/interpretationYounger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality.

Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists be made aware of the potential for marijuana-associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency. In this report, the investigators focus on the known cardiovascular, cerebrovascular, and peripheral effects of marijuana inhalation. Temporal associations between marijuana use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis have been described. In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects.

Abstract Peripheral arterial disease (PAD) is common, but often not diagnosed. A biomarker index would be useful to raise suspicion of PAD, so as to trigger appropriate vascular testing and management. The study comprised 540 individuals: 197 individuals with both coronary artery disease and peripheral arterial disease (CAD + PAD); 81 with CAD only; and 262 with no hemodynamically significant disease (NHSD) of the coronary or peripheral arteries. Multiple linear regression was performed to generate a biomarker panel score that could predict ankle–brachial index (ABI). Logistic regression was used to investigate the relationship between disease status and the panel score as well as other risk factors (e.g. age, diabetes status, smoking status). ROC analysis was performed to test the prediction power of the biomarker panel score. Among the plasma markers tested, beta 2 microglobulin (β2M) and cystatin C had the highest correlation with ABI, and higher than any of the conventional risk factors of age, smoking status, and diabetes status. A biomarker panel score derived from β2M, cystatin C, hsCRP, and glucose had an increased association with PAD status (OR = 12.4, 95% confidence interval (CI) 6.6–23.5 for highest vs lowest quartile), which was still significant after adjusting for known risk factors (OR = 7.3, 95% CI 3.6–14.9 for highest vs lowest quartile). In conclusion, after taking into account the traditional risk factors for PAD, a biomarker panel comprising β2M, cystatin C, hsCRP, and glucose adds useful information to assess the risk of disease.

Objective This study was undertaken to assess the predictive ability of 4 established cardiovascular (CV) risk models for the 10-year risk of fatal and non-fatal CV diseases in European patients with rheumatoid arthritis. Methods Prospectively collected data from the Nijmegen early rheumatoid arthritis (RA) inception cohort was used. Discriminatory ability for CV risk prediction was estimated by the area under the receiver operating characteristic curve. Calibration was assessed by comparing the observed versus expected number of events using Hosmer-Lemeshov tests and calibration plots. Sensitivity and specificity were calculated for the cut-off values of 10% and 20% predicted risk. Results Areas under the receiver operating characteristic curve were 0.78–0.80, indicating moderate to good discrimination between patients with and without a CV event. The CV risk models Systematic Coronary Risk Evaluation (SCORE), Framingham risk score (FRS) and Reynolds risk score (RRS) primarily underestimated CV risk at low and middle observed risk levels, and mostly overestimated CV risk at higher observed risk levels. The QRisk II primarily overestimated observed CV risk. For the 10% and 20% cut-off values used as indicators for CV preventive treatment, sensitivity ranged from 68–87% and 40–65%, respectively and specificity ranged from 55–76% and 77–88%, respectively. Depending on the model, up to 32% of observed CV events occurred in patients with RA who were classified as low risk (<10%) for CV disease. Conclusions Established risk models generally underestimate (Systematic Coronary Risk Evaluation score, Framingham Risk Score, Reynolds risk score) or overestimate (QRisk II) CV risk in patients with RA.

Peripheral arterial disease (PAD) has a significant negative impact on the quality of life of individuals. Understanding the experiences of people living with PAD will be useful in developing comprehensive patient-centred secondary prevention therapies for this population. The aim of this study is to identify first-hand accounts of patients' experiences of living with PAD. Six databases (CINALH, PsyclNFO, MEDLINE, AMED, EMBASE, Social citation index/Science citation index via Web of Science (WOS)) and reference lists of identified studies were searched until September 2017 (updated February 2018). Qualitative studies reporting patients' account of living with PAD were eligible for inclusion. A framework thematic synthesis was implemented. Fourteen studies with 360 participants were included. Pain and walking limitation were recurrent among the varied symptom descriptions. Patients' ignorance and trivialisation of symptoms contributed to delays in diagnosis. Inadequate engagement in disease understanding and treatment decisions meant patients had poor attitudes towards walking treatments and unrealistic expectations about surgery. Depending on symptom progression, patients battle with walking impairment, powerlessness, and loss of independence which were a source of burden to them. Lack of disease understanding is central through patients' journey with PAD and, although they subsequently began adaptation to long term living with PAD, many worried about their future. Disease understanding is vital across the illness trajectory in patients with PAD. Although certain experiences are common throughout patient journey, some might be unique to a particular stage (e.g. unrealistic expectation about surgery, or rationale of walking in spite of pain in a supervised exercise program). Given that PAD is an overarching construct ranging from the mildest form of intermittent claudication to severe critical limb ischemia with ulceration and gangrene, consideration of important patient constructs specific to each stage of the disease may enhance treatment success. Systematic review registration CRD42017070417.

Peripheral artery disease (PAD), which comprises atherosclerosis of the abdominal aorta, iliac, and lower-extremity arteries, is underdiagnosed, undertreated, and poorly understood by the medical community. Patients with PAD may experience a multitude of problems, such as claudication, ischemic rest pain, ischemic ulcerations, repeated hospitalizations, revascularizations, and limb loss. This may lead to a poor quality of life and a high rate of depression. From the standpoint of the limb, the prognosis of patients with PAD is favorable in that the claudication remains stable in 70% to 80% of patients over a 10-year period. However, the rate of myocardial infarction, stroke, and cardiovascular death in patients with both symptomatic and asymptomatic PAD is markedly increased. The ankle brachial index is an excellent screening test for the presence of PAD. Imaging studies (duplex ultrasonography, computed tomographic angiography, magnetic resonance angiography, catheter-based angiography) may provide additional anatomic information if revascularization is planned. The goals of therapy are to improve symptoms and thus quality of life and to decrease the cardiovascular event rate (myocardial infarction, stroke, cardiovascular death). The former is accomplished by establishing a supervised exercise program and administering cilostazol or performing a revascularization procedure if medical therapy is ineffective. A comprehensive program of cardiovascular risk modification (discontinuation of tobacco use and control of lipids, blood pressure, and diabetes) will help to prevent the latter.

Objectives To determine whether gout increases risk of incident coronary heart disease (CHD), cerebrovascular (CVD) and peripheral vascular disease (PVD) in a large cohort of primary care patients with gout, since there have been no such large studies in primary care. Methods A retrospective cohort study was performed using data from the Clinical Practice Research Datalink (CPRD). Risk of incident CHD, CVD and PVD was compared in 8386 patients with an incident diagnosis of gout, and 39 766 age, sex and registered general practice-matched controls, all aged over 50 years and with no prior vascular history, in the 10 years following incidence of gout, or matched index date (baseline). Multivariable Cox Regression was used to estimate HRs and covariates included sex and baseline measures of age, Body Mass Index, smoking, alcohol consumption, Charlson comorbidity index, history of hypertension, hyperlipidaemia, chronic kidney disease, statin use and aspirin use. Results Multivariable analysis showed men were at increased risk of any vascular event (HRs (95% CIs)) HR 1.06 (1.01 to 1.12), any CHD HR 1.08 (1.01 to 1.15) and PVD HR 1.18 (1.01 to 1.38), while women were at increased risk of any vascular event, HR 1.25 (1.15 to 1.35), any CHD HR 1.25 (1.12 to 1.39), and PVD 1.89 (1.50 to 2.38)) but not any CVD. Conclusions In this cohort of over 50s with gout, female patients with gout were at greatest risk of incident vascular events, even after adjustment for vascular risk factors, despite a higher prevalence of both gout and vascular disease in men. Further research is required to establish the reason for this sex difference.

Background: Findings regarding the prevalence of vascular comorbidities in multiple sclerosis (MS) are conflicting. Objective: The objective of this review is to estimate the incidence and prevalence of vascular comorbidities and predisposing comorbidities in persons with MS and to assess the quality of the included studies. Methods: The PubMed, EMBASE, SCOPUS and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles were searched. One reviewer abstracted data using a standardized data collection form, while the second reviewer verified the abstraction. Included studies were assessed qualitatively. Quantitatively, we assessed studies using the I2 statistic, and conducted meta-analyses for population-based studies only. Results: The prevalence of hypertension and hyperlipidemia exceeded 10% in the MS population and increased with age. While the prevalence of ischemic heart disease, congestive heart failure, and stroke were less than 5% overall, the prevalence of these conditions exceeded expectations when compared to the general population. Cardiac valvular disease, however, affected the MS population less often than expected. Problems with study quality were common. Conclusion: Despite the relatively high prevalence of some vascular comorbidities in the MS population, important gaps exist in our understanding of their epidemiology. Most of our knowledge is based on studies conducted in a small number of regions.