Trends in coronary artery disease screening before kidney transplantation

Background: Coronary artery disease (CAD) screening in asymptomatic kidney transplant candidates is widespread but not well supported by contemporary cardiology literature. We describe here temporal trends in CAD screening before kidney transplant in the United States. Methods: Using the United States Renal Data System, we examined Medicare-insured adults who received a first kidney transplant from 2000 through 2015. We stratified analysis based on whether the patient's comorbidity burden met guideline definitions of high-risk for CAD. We examined temporal trends in non-urgent CAD tests within the year prior to transplant and the composite of death and non-fatal myocardial infarction in the 30 days after transplant. Results: Of 94,832 kidney transplant recipients, 37,139 (39%) underwent at least one non-urgent CAD test in the 1 year prior to transplant. From 2000 to 2015, The transplant program waitlist volume had increased as transplant volume stayed constant, while patients in the later eras had slightly higher comorbidity burden (older, longer dialysis vintage, and a higher prevalence of diabetes mellitus and CAD). The likelihood of CAD test in the year prior to transplant increased from 2000 through 2003 and remained relatively stable thereafter. When stratified by CAD risk status, test rates decreased modestly in high-risk patients but remained constant in low-risk patients after 2008. Death or non-fatal myocardial infarction within 30 days after transplant decreased from 3.4% in 2000 to 1.5% in 2015. Nuclear perfusion scan was the most frequent modality of testing throughout examined time periods. Conclusions: CAD testing rates before kidney transplantation have remained constant from 2000 through 2015 despite widespread changes in cardiology guidelines and practice.

58 Effects of sodium–glucose co-transporter 2 (SGLT2) inhibitors on major cardiovascular events in Type 2 diabetic patients: a meta-analysis of randomized controlled trials

Aims Sodium–glucose co-transporter-2 inhibitors (SGLT2i) reduce cardiovascular (CV) events in diabetic patients, with a consistent effect on heart failure (HF) related outcomes. However, the effects on ischaemic CV events appear less certain, in particular in patients with history of HF. The aim of this meta-analysis is to investigate CV benefit of SGLT2i and to assess the effects in patients with and without established atherosclerotic cardiovascular disease (ASCVD), with and without HF, and with estimated glomerular filtration rate < or ≥ 60 mL/min. Methods We searched PubMed, Embase, Cochrane, ISI Web of Science, SCOPUS, and clinicaltrial.gov databases. We performed a systematic review and meta-analysis of randomized, placebo-controlled, cardiovascular outcome trials (CVOT) of SGLT2i in diabetic patients, assessing the effects of SGLT2i on 3-point MACE [CV death, non-fatal myocardial infarction (MI), non-fatal stroke] and composite of HF hospitalization or CV death. Results Of 205 articles, 7 CVOTs were included in the meta-analysis. Compared to placebo, SGLT2i significantly reduced by 10% the risk of 3-point MACE (HR 0.90; P = 0.025) (Figure panel A) and the risk of CV death or HF hospitalization by 24% (HR 0.76; P < 0.001) (Figure panel B). SGLT2i significantly reduced HF hospitalization by 30% (HR 0.70; P < 0.001), with consistent effects in all subgroups analysed, CV death by 17% (HR 0.83; P = 0.035) and all-cause mortality by 18% (HR 0.82; P = 0.024). No significant effects were observed on MI and stroke. Conclusions SGLT2i significantly reduce CV outcome in diabetic patients. SGLT2i remarkably and consistently reduce HF hospitalization, in patients with and without HF at baseline and independently on the presence of ASCVD.

Cardiovascular Events in People With Type 2 Diabetes: Performance of Framingham, UKPDS, and ADVANCE Risk Equations

The aim of this study was to assess the performance of the Framingham, UK Prospective Diabetes Study (UKPDS), and the Action in Diabetes and Vascular disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) risk equations in the prediction of 4-year cardiovascular disease CVD) in Iranian people with type 2 diabetes. The 4-year risks of CVD were estimated using the three equations in a community of 557 patients with type 2 diabetes and free of CVD at baseline. A trained physician evaluated all of the participants regarding the occurrence of CVD events during follow-up. CVD was defined as major events including fatal/non-fatal myocardial infarction as well as fatal/non-fatal stroke, minor events including treated coronary heart disease (CHD), and established peripheral arterial disease (PAD). During four years of follow-up, 64 CVD events were observed (66% minor CVD events). Despite having a good calibration (estimated to observed ratio ranging from 91.37 to 98.2 percent, Hosmer–Lemeshow χ2 (HLχ2) values <15), both general (Framingham) and diabetes-specific (UKPDS and ADVANCE) equations did not have adequate discriminative ability (Area Under the Curve (AUC) ranging from 0.48 to 0.56). Framingham, UKPDS, and ADVANCE risk equations, regardless of being general or diabetes-specific, could not precisely predict 4-year risk of CVD in Iranian individuals with type 2 diabetes.

Implications of Myocardial Infarction on Management and Outcome in Cardiogenic Shock

Background The randomized DOREMI (Dobutamine Compared to Milrinone) clinical trial evaluated the efficacy and safety of milrinone and dobutamine in patients with cardiogenic shock. Whether the results remain consistent when stratified by acute myocardial infarction remains unknown. In this substudy, we sought to evaluate differences in clinical management and outcomes of acute myocardial infarction complicated by cardiogenic shock (AMICS) versus non‐AMICS. Methods and Results Patients in cardiogenic shock (n=192) were randomized 1:1 to dobutamine or milrinone. The primary composite end point in this subgroup analysis was all‐cause in‐hospital mortality, cardiac arrest, non‐fatal myocardial infarction, cerebrovascular accident, the need for mechanical circulatory support, or initiation of renal replacement therapy (RRT) at 30‐days. Outcomes were evaluated in patients with (n=65) and without (n=127) AMICS. The primary composite end point was significantly higher in AMICS versus non‐AMICS (hazard ratio [HR], 2.21; 95% CI, 1.47–3.30; P =0.0001). The primary end point was driven by increased rates of all‐cause mortality, mechanical circulatory support, and RRT. No differences in other secondary outcomes including cardiac arrest or cerebrovascular accident were observed. AMICS remained associated with the primary composite outcome, 30‐day mortality, and RRT after adjustment for age, sex, procedural contrast use, multivessel disease, and inotrope type. Conclusions AMI was associated with increased rates of adverse clinical outcomes in cardiogenic shock along with increased rates of mortality and initiation of mechanical circulatory support and RRT. Contrast administration during revascularization likely contributes to increased rates of RRT. Heterogeneity of outcomes in AMICS versus non‐AMICS highlights the need to study interventions in specific subgroups of cardiogenic shock. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03207165.

Impact of diabetes on coronary severity and cardiovascular outcomes in patients with heterozygous familial hypercholesterolemia: an analysis of genotype and phenotype

Aims Type 2 diabetes mellitus (T2DM) is an independent risk factor for cardiovascular disease. However, the association between T2DM and coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolemia (HeFH) has not been thoroughly evaluated. Our study aimed to assess the effect of T2DM on CAD severity and hard cardiovascular endpoints in a HeFH cohort. Methods A total of 432 patients with HeFH with a molecular and/or clinical Dutch Lipid Clinic Network score ≥6 (definite and probable) were enrolled. Patients were divided into a T2DM group (n=99) and a non-T2DM group (n=333). Hard endpoints included a composite of non-fatal myocardial infarction, stroke, and cardiac death. Results No differences were observed regarding genetic mutations in patients with and without T2DM. Patients with T2DM demonstrated a greater number of diseased vessels (p=0.029) and more severe coronary lesions with high Gensini, SYNTAX, and Jeopardy score tertiles. Compared with patients without T2DM, patients with T2DM were at a significantly greater risk of hard endpoints (multivariate adjusted hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.02–4.84, p=0.025). Additionally, patients with T2DM and good glucose control (HbA1c &lt;7.0%) were at a lower risk of hard endpoints compared with those with poor glucose control (HbA1c ≥7.0%, HR 0.08, 95% CI 0.01–0.56, p=0.011). Conclusions We conclude that T2DM is an independent predictor of CAD severity when assessed by four different tests and worse cardiovascular outcomes, suggesting that T2DM could be further used for risk stratification of patients with HeFH. FUNDunding Acknowledgement Type of funding sources: None. Graphical abstract

Pericoronary adipose tissue attenuation, low-attenuation plaque burden and 5-year risk of myocardial infarction

Introduction Pericoronary adipose tissue (PCAT) attenuation has emerged as a surrogate marker of pericoronary inflammation. To date, no studies have compared the impact of pericoronary adipose tissue (PCAT) attenuation and quantitative plaque burden on cardiac outcomes. Purpose We aimed to establish the relative merits of these approaches to risk prediction and hypothesised that the combination of PCAT attenuation and quantitative plaque burden measures could provide additive and improved prediction of myocardial infarction in patients with stable chest pain. Methods In a post-hoc analysis of a randomized controlled trial, we investigated the association between the future risk of fatal or non-fatal myocardial infarction and PCAT attenuation measured from CT coronary angiography using multivariable Cox regression models including plaque burden, obstructive coronary disease and cardiac risk score (incorporating age, sex, diabetes, smoking, hypertension, hyperlipidaemia and family history of cardiovascular disease). Results In 1697 evaluable participants (mean age 58±10 years), there were 37 myocardial infarctions after a median follow-up of 4.7 [interquartile interval, 4.0–5.7] years. Median low-attenuation plaque burden was 4.20 [0–6.86] % and mean PCAT −76±8 Hounsfield units (HU). PCAT attenuation of the right coronary artery (RCA) was predictive of myocardial infarction (hazard ratio [HR] 1.55, 95% CI 1.08–2.22; p=0.017, per 1 standard deviation increment) with an optimum threshold of −70.5 HU [Hazards ratio (HR) 2.45, 95% CI 1.2–4.9; p=0.01]. Univariable analysis also identified the burden of non-calcified, low-attenuation and calcified plaque as well as Agatston coronary calcium score, presence of obstructive coronary artery disease and cardiovascular risk score were predictors of myocardial infarction (Figure 1). In multivariable analysis, only the low-attenuation plaque burden (HR 1.80, 95% CI 1.16 to 2.81, p=0.011, per doubling) and PCAT-RCA (HR 1.47 95%1.02 to 2.13, p=0.040, per standard deviation increment) remained predictors of myocardial infarction (Figure 1). In multivariable analysis, adding PCAT-RCA ≥-70.5 HU to low-attenuation plaque burden &gt;4% (optimum threshold for future myocardial infarction; HR = 4.87, 95% CI 2.03–11.78; p&lt;0.0001) led to improved prediction of future myocardial infarction (HR 11.7, 95% CI 3.3–40.9; p&lt;0.0001); Figure 2. In ROC analysis, integration of PCAT-RCA attenuation and LAP burden, increased the prediction for myocardial infarction compared to LAP alone (ΔAUC=0.04; p=0.01). Conclusion CT coronary angiography defined PCAT attenuation and low-attenuation plaque have marked and additive predictive value for the risk of fatal or non-fatal myocardial infarction. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Chief Scientist Office of the Scottish Government Health and Social Care Directorates, British Heart Foundation, National Institute of Health/National Heart, Lung, and Blood Institute grant

Progression markers of coronary calcification

Aim To evaluate the relationship between clinical parameters, biomarkers of bone turnover and the progression of coronary artery calcification (CAC) in patients with stable coronary heart disease (CHD) based on long-term (5 years) follow-up. Material and methods The single-center, prospective, non-randomized observational study included 111 men with CHD, admitted for CABG. All patients in the preoperative period underwent the following procedures: color duplex scanning (CDS) of the brachiocephalic arteries (BCA), multi-slice computed tomography (MSCT) coronary angiography to assess the degree of CAC using the Agatson score (calculation of the coronary artery calcium score – CACS), estimation of femoral neck bone mineral density with the T-score calculation and clinical assessment of biomarkers of bone metabolism (calcium, phosphorus, calcitonin, osteopontin, osteocalcin, osteoprotegerin (OPG), alkaline phosphatase, parathyroid hormone). The vital status of patients was ascertained after 3–5 years of follow-up after CABG, CDS of the BCA and MSCT-coronary angiography were repeated. To identify the most significant clinical and anamnestic risk factors and form a model of predictors of CAC progression, patients were divided into two groups depending on the high increase in CACS (an increase in the score of more than 100 Agatston units (AU). Results 16 (14.4%) out of 111 patients failed to establish contact for the next stage of the study. In 4 (3.6%) cases death was registered (3 – fatal myocardial infarction, 1 – fatal stroke). The CAC progression was assessed in 91 patients (81.9%). Patients who showed signs of CAC progression comprised a group of 60 (65.9%) patients; without CAC progression – 31 (34.1%) patients. The “end points” in the groups were comparable and were detected in 18 cases (19.7%): recurrent angina in 16 patients (p=0.368), non-fatal myocardial infarction in 1 (p=0.162) and 1 emergency stenting (p=0,162) of the coronary artery that was not subjected to CABG. The risk model for CAC progression included an initial decrease in femoral neck bone mineral density and nonadherence to statins for 5 years after CABG (p=0.001). Conclusion 65.9% of men with stable CHD showed the signs of CAC progression for 5 years after CABG, according to MSCT. The main predictors of CAC were: low cathepsin K levels and low bone mineral density in the preoperative period, low OPG 5 years post-CABG. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”; 6, Sosnovy Blvd, Kemerovo, 650002, Russia

Meta-analysis assessing cardiovascular outcomes with febuxostat versus allopurinol for patients with gout

Background Gout, the most common inflammatory arthritis in the USA, represents an established risk factor for cardiovascular disease and coronary artery disease mortality. In addition, patients with gout experience an increased risk for non-fatal myocardial infarction, while they might also feature increased risk for stroke. Recent real-world data also highlight the association between gout and atrial fibrillation, which inevitably augments cardiovascular burden. Allopurinol, a xanthine oxidase inhibitor, remains the uric acid-lowering treatment option of first choice, while febuxostat is prescribed, when allopurinol is contraindicated or not tolerated. Unfortunately, medication adherence among gout patients is poor, associated with age and related co-morbidities. Purpose We sought to determine the comparative efficacy of febuxostat versus allopurinol across surrogate cardiovascular outcomes of interest, by pooling data from the 2 dedicated cardiovascular outcome trials available so far. The motive for this analysis was the U.S. Food and Drug Administration (FDA) warning raised after the publication of the CARES trial, regarding the increased risk for cardiovascular and all-cause death with febuxostat compared to allopurinol. Methods We pooled data from the 2 dedicated cardiovascular outcome trials (CARES and FAST) and we assessed the following cardiovascular outcomes of interest: cardiovascular death, all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke, fatal MI, fatal stroke, transient ischemic attack, hospitalization for heart failure, coronary revascularization, cerebrovascular revascularization and atrial fibrillation. Risk of bias was low across the included studies. Results Our analysis in a total of 12,318 patients with gout showed that febuxostat compared to allopurinol treatment does not confer significant risk reduction for any of the assessed, prespecified surrogate outcomes in a study population with significant cardiovascular co-morbidities (Figure 1). One third of patients enrolled in the FAST trial and 40% of the patients enrolled in the CARES trial had pre-existing cardiovascular disease, as depicted in Figure 2. Heterogeneity was low for the vast majority of the assessed outcomes, except for cardiovascular and all-cause death and fatal MI. Conclusions There is no significant difference across surrogate cardiovascular outcomes of interest between febuxostat and allopurinol in patients with gout and cardiovascular co-morbidities. Febuxostat seems to be a safe treatment alternative to allopurinol, despite initial concerns in terms of its cardiovascular safety. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Cardio- and Cerebrovascular Outcomes of Postoperative Acute Kidney Injury in Noncardiac Surgical Patients With Hypertension

Background: The cardiovascular and cerebrovascular risk of postoperative acute kidney injury (AKI) in surgical patients is poorly described, especially in the hypertensive population.Methods: We conducted a retrospective cohort study among all hypertensive patients who underwent elective noncardiac surgery from January 1st, 2012 to August 1st, 2017 at the Third Xiangya Hospital. The primary outcomes were fatal stroke and fatal myocardial infarction (MI). The secondary outcomes were all-cause mortality.Results: The postoperative cumulative mortality within 3 months, 6 months, 1 year, 2 years, and 5 years were 1.27, 1.48, 2.15, 2.15, and 5.36%, for fatal stroke, and 2.05, 2.27, 2.70, 3.37, and 5.61% for fatal MI, respectively, in patients with postoperative AKI. Compared with non-AKI patients, those with postoperative AKI had a significantly higher risk of fatal stroke and fatal MI within 3 months [hazard ratio (HR): 5.49 (95% CI: 1.88−16.00) and 11.82 (95% CI: 4.56−30.62), respectively], 6 months [HR: 3.58 (95% CI: 1.43−8.97) and 9.23 (95% CI: 3.89−21.90), respectively], 1 year [HR: 3.64 (95% CI: 1.63−8.10) and 5.14 (95% CI: 2.50−10.57), respectively], 2 years [HR: 2.21 (95% CI: 1.03−4.72) and 3.06 (95% CI: 1.66−5.64), respectively], and 5 years [HR: 2.27 (95% CI: 1.30−3.98) and 1.98 (95% CI: 1.16−3.20), respectively]. In subgroup analysis of perioperative blood pressure (BP) lowering administration, postoperative AKI was significantly associated with 1-year and 5-year risk of fatal stroke [HR: 9.46 (95% CI: 2.85−31.40) and 3.88 (95% CI: 1.67−9.01), respectively] in patients with ACEI/ARB, and MI [HR: 6.62 (95% CI: 2.23−19.62) and 2.44 (95% CI: 1.22−4.90), respectively] in patients with CCB.Conclusion: Hypertensive patients with postoperative AKI have a significantly higher risk of fatal stroke and fatal MI, as well as all-cause mortality, within 5 years after elective noncardiac surgery. In patients with perioperative administration of ACEI/ARB and CCB, postoperative AKI was significantly associated with higher risk of fatal stroke and MI, respectively.

Variability in body weight and the risk of cardiovascular complications in type 2 diabetes: results from the Swedish National Diabetes Register

Background There is a high incidence of cardiovascular disease in diabetes. Weight variability has been reported as independent risk factor for cardiovascular disease in the general population and preliminarily also in people with type 2 diabetes. Methods Using data from the Swedish National Diabetes Register the possible link between visit-to-visit body weight variability and the risk of cardiovascular complications among people with type 2 diabetes and without prevalent cardiovascular diseases at baseline has been evaluated. Overall, 100,576 people with type 2 diabetes, with at least five measurements of body weight taken over three consecutive years, were included. Variability was expressed as quartiles of the standard deviation of the measures during the three years. The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality and was assessed during five years following the first 3 years of exposure to weight variability. Results After adjusting for known cardiovascular risk factors, the risk of the primary composite outcome significantly increased with increasing body weight variability [upper quartile HR = 1.45; 95% confidence interval 1.39–1.52]. Furthermore, elevated body weight variability was associated with almost all the other cardiovascular complications considered (non-fatal myocardial infarction, non-fatal stroke, all-cause mortality, peripheral arterial disease, peripheral vascular angioplasty, hospitalization for heart failure, foot ulcer, and all-cause mortality). Conclusions High body weight variability predicts the development of cardiovascular complications in type 2 diabetes. These data suggest that any strategy to reduce the body weight in these subjects should be aimed at maintaining the reduction in the long-term, avoiding oscillations.