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Background: Lymphopenia is associated with adverse prognosis in chronic disease states that are related to immune dysregulation. We aimed to determine the association between lymphopenia and mortality in patients presenting to coronary angiography and investigate whether elevated red blood cell distribution width (RDW), an established cardiovascular prognostic marker, further refines risk stratification. Methods: Retrospective analysis of patients undergoing coronary angiography for evaluation or treatment of coronary artery disease between 2003 and 2018. Mortality risk associated with relative (1000–1500/μL) or severe (< 1000/μL) lymphopenia was analyzed using adjusted Cox proportional hazards regression models. Results: Overall, 15,179 patients aged 65 ± 12 years underwent coronary angiography. During a median follow-up of 8 years, 4253 patients died. Compared to normal lymphocyte count, the adjusted hazard ratio (HR) for mortality was 1.31 (95% confidence interval [CI] 1.21–1.41) and 1.97 (95% CI 1.75–2.22) for relative and severe lymphopenia, respectively. The increase in mortality associated with severe lymphopenia was significant in patients presenting in the non-acute setting (HR 2.18, 95% CI 1.74–2.73), ST-segment elevation myocardial infarction (STEMI) (HR 1.59, 95% CI 1.15–2.21), or unstable angina/non-STEMI (HR 2.00, 95% CI 1.70–2.34); p-value for interaction 0.626. The association of lymphopenia with mortality remained significant after additional adjustment to RDW. High RDW (> 14.5%) was associated with reduced survival, and it improved the predictive accuracy of lymphocytes count with an increase in Harrell’s Concordance statistic from 0.634 (SE = 0.005) to 0.672 (SE = 0.005), p < 0.001. Conclusions: lymphopenia is associated with increased risk of mortality during long-term follow-up in patients undergoing coronary angiography, regardless of the coronary presentation. High RDW may enhance the predictive ability of lymphopenia.

Smoking is associated with increased risk for acute ST-elevation myocardial infarction (STEMI) at a young age. Although smoking is a modifiable risk factor, smoking cessation rates after STEMI are suboptimal. We investigated the association between smoking status 1 year after STEMI and adverse events in patients (n = 765) aged ≤60 years. Patients were categorized as: (1) nonsmokers, (2) quit smoking, and (3) continued/resumed smoking. The association between smoking status and risk for major adverse cardiovascular events (MACEs) was analyzed during a median follow-up of 8 years. At presentation with STEMI, the mean age was 51 ± 7 years (88% men) and 427 (56%) were smokers. A year after STEMI, 272 continued smoking, 35 quit but later resumed smoking (summed to a single group; n = 307), and 120 quit smoking. Continued smoking was associated with younger age, male gender, lower weight, and low socioeconomic status. Compared with nonsmokers, the adjusted hazard ratio (95% confidence interval) for myocardial infarction, stroke, unstable angina, death, and MACE was 2.51 (1.67 to 3.73), 2.07 (0.94 to 4.56), 3.73 (1.84 to 7.58), 2.52 (1.53 to 4.13), and 2.40 (1.80 to 3.22), accordingly, in those who continued to smoke. However, the adjusted hazard ratio was not significantly associated with these outcomes in patients who quit smoking (MACE: 1.20 [0.77 to 1.87], p=0.414; nonsignificant for individual end points). In conclusion, the prevalence of smoking in young and middle-aged patients presenting with STEMI is high and smoking cessation rates are low. A year after STEMI, those who continued to smoke had worse cardiovascular outcomes and death compared with nonsmokers; however, the long-term outcomes among those who quit smoking appear to be comparable with nonsmokers. The results highlight the contrast between health benefits of quitting smoking after STEMI and low abstinence rates in clinical practice.

Transfemoral transcatheter aortic valve replacement (TAVR) procedures require secondary vascular access for inserting accessory catheters and performing percutaneous repair of femoral artery injury. Use of the transbrachial approach for secondary vascular access in TAVR procedures has not been reported.This study identified 48 patients at the current institution who had undergone transfemoral TAVR utilising transbrachial secondary vascular access. Efficacy and safety of this strategy for achieving a successful totally percutaneous procedure were examined. Study endpoints were occurrence of vascular complications and bleeding related to transbrachial access, as well as periprocedural and 1-year mortality.Mean patient age was 80±7 years and Society of Thoracic Surgeons Predicted Risk of Mortality score was 10.6±3.1. Sizes of sheaths inserted into the brachial artery were 6 Fr (85%), 8 Fr (2%), and 9 Fr (13%). Transbrachial access was used for delivering stent grafts to the femoral artery in 13% of the patients, inflation of an occlusive balloon within the iliac artery in 10%, and treatment of iatrogenic femoral artery stenosis in 2%. Successful valve replacement was achieved in all cases. Brachial sheaths were removed by manual compression following administration of protamine sulfate. There were no major access site complications or VARC-3 type ≥2 bleeding related to the brachial vascular access. Brachial artery occlusion occurred in two patients (4%) who underwent surgical vascular repair. Two (2) additional patients developed mild arm ischaemia, which was treated conservatively. Periprocedural mortality was 0% and early mortality was 8%.Transbrachial secondary access in TAVR procedures was feasible and enabled percutaneous vascular repair in cases of femoral artery injury.

Background: Guideline-directed medical therapies for heart failure (HF) may benefit patients with reduced left ventricular ejection fraction (LVEF) following acute coronary syndromes (ACS). Few real-world data are available regarding the early implementation of HF therapies in patients with ACS and reduced LVEF. Methods: Data collected from the 2021 nationwide, prospective ACS Israeli Survey (ACSIS). Drug classes included: (a) angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitors (ARNI); (b) beta-blockers; (c) mineralocorticoid receptor antagonist (MRA) and (d) sodium-glucose cotransporter-2 inhibitors (SGLT2I). The utilization of HF therapies at discharge or 90 days following ACS was analyzed in relation to LVEF [reduced ≤40% (n = 406) or mildly-reduced 41–49% (n = 255)] and short-term adverse outcomes. Results: History of HF, anterior wall myocardial infarction and Killip class II-IV (32% vs. 14% p < 0.001) were more prevalent in those with reduced compared to mildly-reduced LVEF. ACEI/ARB/ARNI and beta-blockers were used by the majority of patients in both LVEF groups, though ARNI was prescribed to only 3.9% (LVEF ≤ 40%). MRA was used by 42.9% and 12.2% of patients with LVEF ≤40% and 41–49%, respectively, and SGLT2I in about a quarter of both LVEF groups. Overall, ≥3 HF drug classes were documented in 44% of the patients. A trend towards higher rates of 90-day HF rehospitalizations, recurrent ACS or all-cause death was noted in those with reduced (7.6%) vs. mildly-reduced (3.7%) LVEF, p = 0.084. No association was observed between the number of HF drug classes or the use of ARNI and/or SGLT2I with adverse clinical outcomes. Conclusions: In current clinical practice, the majority of patients with reduced and mildly-reduced LVEF are treated by ACEI/ARB and beta-blockers early following ACS, whereas MRA is underutilized and the adoption of SGLT2I and ARNI is low. A greater number of therapeutic classes was not associated with reduced short-term rehospitalizations or mortality.

Hypertension is a well-established risk factor for the onset and progression of atrial fibrillation (AF). Blood pressure (BP) measurements during routine exercise stress testing (EST) may identify subjects at increased risk for developing AF. We performed a retrospective analysis of treadmill EST carried out using the Bruce protocol in patients aged ≥40 years without a history of AF (n = 17,617; 42% women). BP was measured at rest, peak exercise, and 2-min recovery and analyzed for its association with the risk for developing AF. During a mean follow-up of 7 years, AF was documented in 4.5% of the patients. The incidence rate of AF per 1000 person-years increased with the rise in CHA

Background Estimation of kidney function by glomerular filtration rate (eGFR) is affected by age and is important for decision making regarding treatment and prognosis of patients with cardiovascular disease. We investigated the impact of eGFR on long-term cardiovascular outcomes in an elderly population undergoing coronary angiography for evaluation or treatment of coronary artery disease. Methods GFR was estimated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in 3690 elderly patients (aged 70-100 years) undergoing coronary angiography. Patients receiving maintenance dialysis were excluded. The association between eGFR and major adverse cardiovascular events (MACE) including myocardial infarction, ischemic stroke or death, was investigated. GFR was further calculated according to modification of diet in renal disease (MDRD) and the Cockcroft-Gault equations, and compatibility between estimations was analyzed. Results Cardiovascular comorbidities were more prevalent with the reduction in kidney function as was the proportion of patients presenting with acute coronary syndromes. The adjusted hazard ratio (95% confidence interval) for MACE during a mean follow-up of 5 years was 0.95 (0.77-1.16), 1.04 (0.84-1.29), 1.56 (1.16-1.84), 2.22 (1.65-2.97) and 3.74 (2.20-6.38) in patients with eGFR 60-89, 45-59, 30-44, 15-29 and 90 ml/min/1.73m2. Reclassification of eGFR stages by MDRD (upward 23.8%, downward 0.4%) and Cockcroft-Gault (upward 4.3%, downward 28.1%) compared to CKD-EPI estimation, was noted. However, the association between eGFR stages and MACE was similar between equations. Conclusions Kidney function, as manifested by eGFR, has a graded inverse association with the burden of cardiovascular comorbidities and long-term adverse events in elderly patients undergoing coronary angiography.

Hypertension, obesity, and low cardiorespiratory fitness (CRF) are known risk predictors for the development of atrial fibrillation (AF) that often interrelate with each other. We examined the interplay of these 3 risk indicators with the occurrence of AF in patients without known cardiovascular disease.A retrospective analysis of 13,042 patients underwent exercise stress testing (EST). The occurrence of AF during the median follow-up period of 6.8 years was investigated in relation to the presence of obesity (body mass index ≥30 kg/mThe mean age of the study population was 58 ± 9 years; 49% were women. AF occurred in 499 patients (3.8%). Obesity [hazard ratio (95% confidence interval)], 1.36 (1.12-1.65), hypertension, 1.47 (1.19-1.82), and low CRF, 1.32 (1.06-1.64), were independent risk predictors for AF after multivariable adjustment, including after adjusting for each other and also when the risk predictors were analyzed as continuous variables. In a combined model, a gradual increase in the risk of AF was observed, reaching an adjusted hazard ratio of 2.53 (1.77-3.62) in those with all 3 compared with neither risk indicators. P-for-interaction between hypertension and obesity, or hypertension and low CRF was nonsignificant.Obesity, low CRF, and hypertension are independently associated with an excess risk of developing AF in patients without known cardiovascular disease, both individually and more so when coexisting together.

Heart rate response during exercise testing (ET) provides valuable prognostic information. Limited data are available regarding the prognostic interplay of heart rate (HR) measured at rest, exercise and recovery phases of ET, and its ability to predict risk beyond exercise capacity.Retrospective analysis of treadmill ETs was performed by the Bruce protocol in patients aged 35-75 yr without known cardiovascular disease (CVD; n = 13 887; 47% women). Heart rate recovery at 2 min (HRR2; defined abnormal42 beats) and chronotropic index (CI; defined abnormal80%, determined as age-predicted HR reserve) were analyzed in association with the risk of developing myocardial infarction, stroke, or death (major adverse cardiovascular event [MACE]) during median follow-up of 6.5 yr.The HRR242 beats and CI80% were each associated with increased risk of MACE: adjusted hazard ratios with 95% confidence interval 1.47: 1.27-1.72 and 1.66: 1.42-1.93, P.001, respectively, evident also when analyzed as continuous variables. Strength of association of HRR2 and CI with outcome was attenuated but remained significant with further adjustment for exercise duration and metabolic equivalents. Having both HRR2 and CI abnormal compared with only one measure abnormal was associated with hazard ratios with 95% confidence interval of 1.66: 1.38-2.00 and 1.48: 1.22-1.79 for MACE, before and after adjustment for cardiorespiratory fitness (CRF). The degree of CRF (low vs mid/high) did not modify the prognostic effect of HRR2 and CI (P-for-interaction nonsignificant).Both HRR2 and CI provide independent prognostic information beyond CRF in patients without CVD referred for ET. The predictive ability is more pronounced when both abnormal HR measures coexist.

Background Risk factors control and secondary prevention measures are often reported to be suboptimal in patients undergoing coronary artery bypass grafting (CABG) and may lead to worse clinical outcomes. We aimed to examine potentially modifiable risk factors in patients undergoing CABG and investigate their association with long-term coronary events. Methods Cardiovascular risk factors were recorded preoperatively in the setting of a cardiac catheterization laboratory and were analyzed in relation to long-term coronary events, defined as acute coronary syndrome (ACS) or revascularization after CABG. Results Study population included 1,125 patients undergoing CABG without previous revascularization. Modifiable risk factors included hypertension (71%), hyperlipidemia (67%), diabetes (42%), obesity (28%), and smoking (21%). Only 8% did not have any of the five risk factors. During the mean follow-up of 93 ± 52 months after CABG, 179 patients (16%) experienced a coronary event. Incidence rates were higher in patients with than without the presence of each of the modifiable risk factors, except obesity. Active smoking (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: (1.07–2.13); p = 0.020), presence of diabetes (HR: 1.61; 95% CI: 1.18–2.18; p = 0.002), and hyperlipidemia (HR: 2.13; 95% CI: 1.45–3.14; p Conclusions In patients undergoing CABG, diabetes, hyperlipidemia, and smoking, as documented preoperatively, were potentially modifiable risk factors that were independently and cumulatively associated with long-term risk of ACS or coronary revascularization, highlighting the importance of early identification and risk factors control for improving cardiovascular health after CABG.

Patients with acute coronary syndrome (ACS) are at high-risk for recurrent coronary syndromes, heart failure and death. Early coronary intervention combined with medications reduces these risks. The ACS Israeli Survey (ACSIS) is conducted over a 2-month period, every 2-3 years. ACSIS includes all patients discharged with a diagnosis of ACS from the 24 coronary care units and cardiology departments in Israel. We compared clinical profiles and 1-year survival between ACS patients who did and did not undergo coronary angiography.We reviewed ACSIS for the period 2002-2013.The prognosis of patients who did not undergo coronary angiography during hospitalization (N = 2078) was significantly worse than for patients who underwent angiography (N = 9550). Avoidance of angiography was less common in ST-elevation myocardial infarction (STEMI) patients than in non-STEMI/unstable angina (NSTEMI/UAP) patients (13% vs. 22%, p 0.001). Among NSTEMI/UAP patients, those who did not undergo angiography were older (mean: 71 vs. 64 years, p 0.001), had higher incidences of diabetes (47% vs. 38%, p 0.001), and renal (55% vs. 27%, p 0.001) and heart failure (35% vs. 13%, p 0.01) on admission, compared to those who underwent angiography. Even patients that underwent only diagnostic angiography had had a better prognosis than patients who did not undergo angiography. After propensity score matching for the major differences mentioned above, survival was still significantly better for patients who underwent angiography.ACS patients who did not undergo coronary angiography had higher-risk clinical profiles and worse 1-year survival than ACS patients who underwent angiography. After propensity score matching, the absence of angiography was independently associated with higher mortality.Data over 10 years were reviewed from a national registry of acute coronary syndrome. Patients who did not undergo coronary angiography during hospitalization were older and with more comorbidities than patients who underwent angiography. After propensity score matching, the absence of angiography remained independently associated with 1-year mortality.

Involvement of atherosclerosis in extracardiac vascular territories may identify coronary artery disease (CAD) patients at higher risk for adverse events. We investigated the long-term prognostic implications of polyvascular disease in patients with CAD, and further analyzed lipid goal attainment and its relation to patient outcomes. The study was a retrospective analysis of 10,297 patients who underwent coronary revascularization, categorized as having CAD alone (83.1%) or with multisite artery disease (MSAD) (16.9%) including cerebrovascular disease (CBVD) and/or peripheral artery disease (PAD). Incidence rates and hazard ratios (HR) for major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or all-cause death) according to vascular territories involved, and in relation to most-recent lipid levels attained, were analyzed. Patients with MSAD were older with higher burden of co-morbidities. The rate of MACE (myocardial infarction, ischemic stroke, or all-cause death) and its individual components increased with the number of affected vascular beds. Adjusted HR (95% confidence interval) for MACE was 1.41 (1.24 to 1.59) in patients with CAD and CBVD, 1.46 (1.33 to 1.62) in CAD and PAD, and 1.69 (1.49 to 1.92) in those with CAD and CBVD and PAD, compared with CAD alone. Most-recent low-density lipoprotein cholesterol (LDL-C) levels55 mg/dl and70 mg/dl were attained by 21.8% and 44.6% of patients with CAD alone, in comparison to 22.7% and 43.3% in MSAD. Compared with patients with most-recent LDL-C100 mg/dl, attaining LDL-C70 mg/dl had an adjusted HR for MACE of 0.52 (0.47 to 0.57) in CAD only patients and 0.66 (0.57 to 0.78) in MSAD patients. In conclusion, the presence of CBVD and/or PAD in patients with CAD is associated with higher burden of co-morbidities and progressive increase in long-term MACE. More than half of CAD patients with or without MSAD do not achieve lipid goals, which are associated with a significantly lower risk for adverse events.

AimsThe evidence are not conclusive that a small incremental increase in door-to-balloon (D2B) time leads to a significant increase in death of ST-elevation myocardial infarction (STEMI) patients. In a previous study, we described a quality improvement intervention that reduced D2B time in 333 patients with STEMI. The aim of the current study was to compare mortality rates of the patients, before and after the intervention.Methods and resultsWe examined the survival of 133 consecutive patients with STEMI treated prior to an intervention to decrease D2B time and 200 treated after the intervention. The mortality rate was the same before and after the quality intervention. The median D2B time for the entire cohort was 55 min. The number of patients with D2B time >55 min prior to the intervention was 82/133 (61%) and after the intervention 74/200 (37%) P 55 min was 15/155 (9.7%), P 55 min was 3.7 (1.3–10.4).ConclusionMortality and non-fatal complications did not differ significantly between STEMI patients before and after a quality improvement intervention. However, the number of patients treated within 55 min from arrival was significantly higher after the intervention; and coronary intervention within this time was associated with a lower death rate.

Body-mass index (BMI) is a risk marker and therapeutic target in cardiovascular prevention. The effect of changes in BMI on mortality in patients with cardiovascular diseases has not been completely delineated. We aimed to assess the association between percent change in BMI, as measured 3-years after cardiac catheterization, and long-term mortality. Patients who underwent cardiac catheterization (n = 11,220; mean age 63 ± 10 years) were categorized according to BMI groups (normal-weight, 18.50 to 24.99 kg/m2; overweight, 25.00 to 29.99 kg/m2; obesity, ≥30 kg/m2). Follow-up BMI was considered the level measured closest to the timepoint of 3 years post catheterization. Percent change in BMI was calculated and its association with long-term all-cause mortality was investigated. Change in BMI of ±5% was observed in 46% of the patients, a decrease >5% in 15.5%, and an increase of >5% of BMI in 38.5%. Compared with those with the lowest change in BMI (±5%), the adjusted hazard ratios for mortality were 1.45 (95% confidence interval [CI], 1.27 to 1.65), and 1.69 (1.46 to 1.95) in patients with 5% to 10% and >10% decrease in BMI, respectively, and 1.05 (0.94 to 1.17), 1.15 (1.03 to 1.28), and 1.40 (1.19 to 1.64) in patients with 5% to 10%, 10% to 20% and >20% increase in BMI, respectively. The pattern was similar in normal-weight, overweight, and obese subgroups at baseline. However, the magnitude of the association with decrease BMI was more pronounced in normal-weight patients (P-for-interaction 0.031). In conclusion, the association of percent changes in BMI after cardiac catheterization and all-cause mortality had a reversed J-shaped pattern, with both weight loss and weight gain being associated with increased risk. A decrease in BMI was related to higher mortality rates than was an increase in BMI for a comparable degree of percent change.

Background Although there is a diminishing role of exercise stress testing (EST) in the diagnostic assessment of coronary heart disease, the physiologic response to exercise may provide valuable prognostic information. We aimed to investigate the association of repeated blood pressure (BP) measurements during EST with long-term risk of myocardial infarction, stroke or death (MACE), as well as the development of new-onset hypertension. Methods Retrospective analysis of EST performed between the years 2005–2019 in a single center according to Bruce protocol. Included were patients aged 35–75 years without a history of cardiovascular disease (n=14,792; 48% women). BP was documented at rest, submaximal exercise (Bruce stage-2), peak exercise and recovery (2 minutes). Association of BP measures with study outcomes during a median follow-up of 78 months was investigated. Results An increment of 10-mmHg in rest, submaximal, peak and recovery systolic BP was each associated with a significant increase in the hazard ratio (HR) and 95% confidence interval (CI) for MACE: 1.09 (1.04–1.14), 1.06 (1.01–1.10), 1.04 (1.01–1.08), and 1.06 (1.02–1.10), respectively, after adjustment including exercise capacity, medications and resting BP. The association between SBP at submaximal exercise and recovery with MACE had a J-shaped appearance (Figure). Among non-hypertensive patients without BP lowering medications (n=8,529), 13% were diagnosed with new-onset hypertension during follow-up. Excessive systolic BP response to peak exercise (≥190 mmHg in women and ≥210 mmHg in men) was an independent predictor of future hypertension [HR (95% CI)]: 1.87 (1.41–2.48), as were systolic BPs during submaximal exercise [>160 vs. ≤130 mmHg: 2.44 (1.97–3.03)] and recovery [≥140 vs. ≤120 mmHg: 1.65 (1.37–1.98)], showing gradual, incremental association with the risk for developing hypertension. Conclusions BP measurement during exercise and recovery phases of treadmill testing provides incremental prognostic information regarding long-term risk for cardiovascular events and the probability for developing future hypertension. Funding Acknowledgement Type of funding sources: None.

Background The increased risk for cardiovascular events in diabetics is heterogeneous and contemporary clinical risk score calculators have limited predictive value. We therefore examined the additional value of coronary artery calcium score (CACS) in outcome prediction in type 2 diabetics without clinical coronary artery disease (CAD). Methods The study examined a population-based cohort of type 2 diabetics (n = 735) aged 55–74 years, recruited between 2006 and 2008. Patients had at least one additional risk factor and no history or symptoms of CAD. Risk assessment tools included Pooled Cohort Equations (PCE) and Multi-Ethnic Study of Atherosclerosis (MESA) 10-year risk score calculators and CACS. The occurrence of myocardial infarction (MI), stroke or cardiovascular death (MACE) was assessed over 10-years. Results Risk score calculators predicted MACE and MI and cardiovascular death individually but not stroke. Increasing levels of CACS predicted MACE and its components independently of clinical risk scores, glycated hemoglobin and other baseline variables: hazard ratio (95% confidence interval) 2.92 (1.06–7.86), 6.53 (2.47–17.29) and 8.3 (3.28–21) for CACS of 1–100, 101–300 and > 300 Agatston units respectively, compared to CACS = 0. Addition of CACS to PCE improved discrimination of MACE [AUC of PCE 0.615 (0.555–0.676) versus PCE + CACS 0.696 (0.642–0.749); p = 0.0024]. Coronary artery calcium was absent in 24% of the study population and was associated with very low event rates even in those with high estimated risk scores. Conclusions CACS in asymptomatic type 2 diabetics provides additional prognostic information beyond that obtained from clinical risk scores alone leading to better discrimination between risk categories.

Aims The increased risk for cardiovascular events in diabetics is heterogeneous and contemporary clinical risk score calculators have limited predictive value. We therefore examined the additional value of coronary artery calcium score (CACS) in outcome prediction in type 2 diabetics without clinical coronary artery disease (CAD). Methods and results The study examined a prospective population-based cohort of type 2 diabetics (n=735) aged 55–74 years, recruited between 2006–2008. Patients had at least one additional risk factor and no history or symptoms of CAD. Risk assessment tools included Pooled Cohort Equations (PCE) and Multi-Ethnic Study of Atherosclerosis (MESA) 10-year risk score calculators and CACS. The occurrence of MI, stroke or cardiovascular death (MACE) was assessed over 10-years. Risk score calculators predicted MACE and MI and cardiovascular death individually but not stroke. Increasing levels of CACS predicted MACE and its components independently of clinical risk scores, glycated hemoglobin and other baseline variables: hazard ratio (95% confidence interval) 2.92 (1.06–7.86), 6.53 (2.47–17.29) and 8.3 (3.28–21) for CACS of 1–100, 101–300 and >300 Agatston units respectively, compared to CACS=0. Addition of CACS to PCE improved discrimination of MACE [AUC of PCE 0.615 (0.555–0.676) vs PCE + CACS 0.696 (0.642–0.749); p=0.0024[. Coronary artery calcium was absent in 24% of the study population and was associated with very low event rates even in those with high estimated risk scores. Conclusions CACS in asymptomatic type 2 diabetics provides additional prognostic information beyond that obtained from clinical risk scores alone leading to better discrimination between risk categories. Funding Acknowledgement Type of funding sources: None.

Objectives Estimation of kidney function by glomerular filtration rate (eGFR) is affected by age and is important for decision making regarding treatment and prognosis of patients with cardiovascular disease. We aimed to investigate the impact of eGFR on long-term cardiovascular outcomes in an elderly population undergoing coronary angiography for evaluation or treatment of coronary artery disease. Methods GFR was estimated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in 3,690 elderly patients (aged 70–100 years) undergoing coronary angiography. Patients receiving maintenance dialysis were excluded. The association between eGFR and long-term major adverse cardiovascular events (MACE) including myocardial infarction, ischemic stroke or death, was investigated. GFR was further calculated according to Modification of Diet in Renal Disease (MDRD) and the Cockroft-Gault equations, and compatibility between estimations was analyzed. Results Cardiovascular comorbidities were more prevalent with the reduction in kidney function as was the proportion of patients presenting with acute coronary syndromes. The adjusted hazard ratio (95% confidence interval) for MACE during a mean follow-up of 5 years was 0.98 (0.80–1.19), 1.05 (0.85–1.30), 1.45 (1.15–1.82), 2.20 (1.64–2.95) and 3.87 (2.28–6.58) in patients with eGFR 60–89, 45–59, 30–44, 15–29 and 90 ml/min/1.73m2. Reclassification of eGFR stages by MDRD (upward 23.8%, downward 0.4%) and Cockroft-Gault (upward 4.3%, downward 28.1%) compared to CKD-EPI estimation, was noted. However, the association between eGFR stages and MACE was similar between equations. Conclusions Kidney function, as manifested by eGFR, has a graded inverse association with the burden of cardiovascular comorbidities and long-term adverse events in elderly patients undergoing coronary angiography. Funding Acknowledgement Type of funding sources: None.

Background: Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for coronary artery disease (CAD). However, its role in real-world practice and implications for clinical care remains limited. Under investigation herein, are the clinical characteristics associated with increased Lp(a) levels in patients presenting with acute coronary syndrome (ACS). Methods: Lp(a) was measured at admission in patients ≤ 65 years of age presenting with ACS in a single center. Logistic regression model was used to determine the independent association of clinical characteristics with elevated Lp(a). Results: A total of 134 patients were screened for Lp(a); 83% males, mean age 52 ± 8 years. Median Lp(a) level was 46 nmol/L (interquartile range [IQR] 13–91). Elevated Lp(a) > 72 nmol/L (30 mg/dL) was documented in 32% and associated with younger age at CAD diagnosis. In a multiple logistic regression model, premature CAD (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.48–10.07, p = 0.06), previous revascularization (OR 2.56, 95% CI 1.17–5.59, p = 0.019) and probable/definite familial hypercholesterolemia (FH) (OR 3.18, 95% CI 1.10–9.21, p = 0.033), were independently associated with elevated Lp(a). In contrast, Lp(a) levels were not associated with other traditional cardiovascular risk factors, previous statin treatment, C-reactive protein level or ACS type. Conclusions: In young and middle-aged patients presenting with ACS, premature CAD, previous revascularization and FH were independently associated with elevated Lp(a), indicating progressive CAD and higher cardiovascular risk. These results, are in accordance with guideline based recommendations for Lp(a) screening, and may be of importance in addressing residual cardiovascular risk in young ACS patients, in light of the novel emerging therapies targeting Lp(a).

Disturbances in glucose and lipid homeostasis are cardinal features of the metabolic syndrome that affect millions of people worldwide. These conditions have multi-organ impact, and while cardiovascular effects are usually the core for studies and preventive measures, other systems may also be affected, including the pancreas. Acute pancreatitis related to severe hypertriglyceridemia is an under-recognized condition that could lead to significant morbidity and mortality. Therefore, when suspected, prompt diagnosis and treatment should be initiated to cover the various aspects of this disorder. Though commonly known to be associated with excess of alcohol use, hypertriglyceridemia-related pancreatitis is particularly observed in diabetics, especially when uncontrolled. Here, we portray the possible mechanisms and clinical features that link type 2 diabetes, hypertriglyceridemia and pancreatitis, and discuss their health-related outcomes and the current and novel treatment options for this unique disease.

Objective To establish and compare the effectiveness of two medetomidine-based immobilization protocols in Persian fallow deer (Dama dama mesopotamica). Study design Prospective, randomized, blinded clinical study. Animals A group of 31 captive Persian fallow deer. Methods Deer scheduled for translocation were immobilized with a combination of medetomidine (76 ± 11 μg kg−1) and ketamine (1.0 ± 0.2 mg kg−1) (MK; n = 15) or medetomidine (77 ± 11 μg kg−1) and midazolam (0.10 ± 0.01 mg kg−1) (MM; n = 16) administered intramuscularly. An observer unaware of group assignments recorded times to immobilization and recovery, monitored physiologic variables and scored the quality of induction, immobilization and recovery (scale 1–5: 1, poor; 5, excellent). Atipamezole was administered for reversal. Data analysis was performed using the t test, the Mann–Whitney U test, the chi-square test and the Fisher's exact test. Significance was set at p Results Data are presented as mean ± standard deviation or median (range). Time to induce immobilization was 9 ± 4 and 10 ± 4 minutes in the MK and MM groups, respectively. Immobilization quality score was 5 (1–5) following both combinations. Hemoglobin oxygen saturation (SpO2) was significantly lower in the MK (80 ± 8%) than in the MM group (87 ± 8%) although respiratory frequency did not differ between MK and MM (11 ± 5 and 10 ± 2 breaths minute−1, respectively). Recovery times were 13 ± 6 (MK) and 14 ± 7 minutes (MM) and did not differ between groups. No morbidities or mortalities were recorded during 1 month after immobilization. Conclusions and clinical relevance The MK and MM combinations produced sufficient immobilization in captive Persian fallow deer for short nonpainful procedures. Based on the SpO2 values, the MM combination may be associated with less respiratory depression; nevertheless, both combinations may result in a decrease in SpO2.

Objectives The authors used coronary computed tomography angiography (CTA) to determine plaque characteristics predicting individual late plaque events precipitating acute coronary syndromes (ACS) in a cohort of asymptomatic type 2 diabetic patients. Background In patients with coronary artery disease, CTA plaque characteristics may predict mid-term patient events. Methods Asymptomatic patients with diabetes 55 to 74 years of age with no history of coronary artery disease (N = 630) underwent baseline 64-slice CTA and detailed plaque level analysis. All subsequent clinical events were recorded and adjudicated. In patients who developed ACS, culprit plaque was identified at invasive angiography and its precursor located on the baseline CTA. Plaque characteristics predicting an ACS-associated culprit plaque event were analyzed by time to event accounting for inpatient clustering of plaques and competing events. Results Among 2,242 plaques in 499 subjects, 24 ACS culprit plaques were identified in 24 subjects during median follow-up of 9.2 years (interquartile range: 8.4 to 9.8 years). Plaque volume (upper vs. lower quartile hazard ratio [HR]: 6.9; 95% confidence interval [CI]: 1.6 to 30.8; p = 0.011), percentage of low-density plaque content Conclusions In asymptomatic patients with type 2 diabetes, CTA plaque volume, percent low-density plaque content, and mild calcification predicted late plaque events. The additional presence of luminal stenosis increased the probability of an acute event.

Background Aortic regurgitation (AR) following transcatheter aortic valve replacement (TAVR) is usually due to paravalvular leak, is more common with self-expanding valves and is associated with adverse outcomes. Treatment of AR with a second valve (valve-in-valve) has been reported, however the mechanism of benefit is unclear. We hypothesized that location of the initial valve in relation to the aortic annulus should guide positioning of the second valve. Methods We assessed the outcomes of valve-in-valve deployment for treatment of AR following implantation of self-expanding valves in a single-center TAVR registry. Location of the initial valves was defined as supra-annular, intra-annular or infra-annular according to the position of the device pericardial skirt relative to the annulus. Positioning of the second valve was selected according to the location of the initial valves. Results Among 285 TAVR patients who received Corevalve or Evolut-R valves, 11 (3.8%) underwent valve-in-valve deployment due to AR. Position of initial valves was supra-annular in 6 cases (group-1), intra-annular in 3 cases (group-2) and infra-annular in 2 cases (group-3). In group-1, second valves were implanted 9 ± 4 mm lower than the initial valves. In group-2, second valves were implanted 7 ± 4 mm higher than the initial valves. In group-3, second valves were implanted 9 ± 1 mm higher than the initial valves. Valve-in-valve deployment reduced AR grade in all 3 groups. Conclusions Valve-in-valve deployment decreased AR grade during TAVR procedures. We suggest that positioning of the second valve should be guided by the location of the initial valve relative to the aortic annulus.

The diagnosis of severe hypertriglyceridemia (HTG) as a cause for acute pancreatitis is often delayed with limited data on the characteristics and predictors of recurrent pancreatitis in this population.A regional database of severe HTG level of 1000 mg/dL or greater was analyzed to identify subjects with acute pancreatitis. Factors associated with recurrent pancreatitis during long-term follow-up were investigated.Severe HTG-associated pancreatitis was evident in 171 patients (75% diabetics). Recurrent pancreatitis was observed in 16%; this was associated with younger age, alcohol abuse, and an increase in triglyceride levels. In multivariable analysis, peak triglycerides level of greater than 3000 mg/dL (hazard ratio, 2.92; 95% confidence interval, 1.28-6.64; P = 0.011) and most recent triglycerides level of greater than 500 mg/dL (hazard ratio, 3.72; 95% confidence interval, 1.60-8.66; P = 0.002) remained independently associated with recurrent pancreatitis. These lipid measures as well as alcohol abuse were additionally correlated with a stepwise increase in the number of pancreatitis episodes.Severe HTG-related pancreatitis was closely associated with diabetes. Extreme HTG and a lack of attainment of lower triglyceride levels were independent long-term predictors of recurrent pancreatitis. These findings emphasize the importance of early identification and successful treatment of severe HTG and its underlying disorders to reduce the burden of recurrent pancreatitis.

Introduction A retrospective/prospective observational study was conducted to explore the current management of hyperlipidaemia in high-risk (HR) and very high risk (VHR) patients in central/eastern Europe and Israel. Methods The study enrolled adult patients who were receiving lipid-lowering therapy and attending a specialist (cardiologist/diabetologist/lipidologist) or internist for a routine visit at 57 sites (including academic/specialist/internal medicine centres) across Bulgaria, Croatia, Czech Republic, Israel, Poland, Romania and Slovakia. Data were collected from medical records, for the 12 months before enrolment, with/without ≤ 6 months’ additional prospective follow-up. Results A total of 1244 patients, mean (SD) age 63.3 (11.3) years were included (307 with familial hypercholesterolaemia (FH), 943 secondary prevention patients). Almost all patients (98.1%) were receiving statins (76.7% monotherapy/21.4% combined therapy), with 53.1% receiving high-intensity statin therapy: 127 patients (10.2%) had adverse events attributed to statin intolerance. Mean (SD) low density lipoprotein cholesterol (LDL-C) levels were 3.3 (1.7) mmol/L at the first, and 2.7 (1.3) mmol/L at the last, visit of the retrospective phase of observation, with little change during the prospective phase. Less than one-quarter (23.8%; 95% CI 17.29–31.45%) of HR patients and less than half (42.0%; 39.05–44.98%) of VHR patients achieved their risk-based LDL-C targets of

OBJECTIVES The choice of a bioprosthetic valve (BV) over a mechanical valve (MV) in middle-aged adults in the mitral position is still under debate. Each valve type has benefits and drawbacks. We examined the mid-term survival of patients aged 50–70 years after BV versus MV mitral valve replacement (MVR). METHODS We conducted a multicentre, retrospective analysis of patients aged 50–70 years undergoing MVR from 2005 to December 2018 in 4 medical centres in Israel. To control for between-group differences, we used propensity-adjusted analysis. The primary end point was all-cause mortality. Secondary end points included reoperation, cerebrovascular accident and bleeding. RESULTS During the study period, 2125 MVR procedures were performed. Of these, 796 were eligible for inclusion [539 (67.8%) MV replacement and 257 (32.2%) BV]. The mean age was 61.0 ± 5.4. There were 287 deaths during 4890 person-years of follow-up. The adjusted hazard ratio was (1.13 [0.85–1.49], P = 0.672). There was also no difference in the secondary end points. Subgroup analysis of patients aged 50–64 years showed a higher risk of mortality with BV (hazard ratio = 1.50 [1.07–2.1], P = 0.018). Reoperation was a strong predictor of mortality during the study period (72.2%). CONCLUSIONS In patients aged 50–70 years, we found an interaction between age and MV or BV outcomes—those younger than 65 years gained a mortality advantage with MV, while outcomes were similar in the 65–70 age group. this supports the current guidelines recommending using MV in patients

Background Transcatheter aortic valve replacement (TAVR) is preferably performed as a completely percutaneous procedure via transfemoral access. Suture-mediated vascular closure devices are deployed prior to sheath insertion (pre-closure). Inability to perform pre-closure may necessitate surgical vascular repair of the femoral artery. Patients at increased risk of vascular surgery complications may benefit from a percutaneous method for achieving access site haemostasis. Stent graft implantation is commonly used for treating access site injury following TAVR. This study assessed the feasibility of a strategy of planned stent graft implantation within the femoral artery for achieving access site haemostasis in patients undergoing transfemoral TAVR and in whom vascular pre-closure was not possible. Methods A prospective institutional TAVR registry was retrospectively analysed and a cohort of patients were identified who were selected for transfemoral valve delivery and in whom pre-closure failed and access site haemostasis was achieved by stent graft implantation. Results This strategy was used for achieving access site haemostasis in 11 patients (1.5% of 744 patients undergoing transfemoral TAVR). These patients were considered to be at increased risk of vascular surgery complications due to advanced age, frailty, comorbidities, or immobility. Stent graft implantation achieved access site haemostasis in all patients. During follow-up, 30-day mortality was zero, 1-year mortality was 27%, and none of the patients required additional vascular interventions. Conclusion The preliminary data suggest that planned stent graft implantation within the femoral artery may achieve access site haemostasis and enable a totally percutaneous TAVR procedure, despite failure to perform pre-closure with a suture-based vascular closure device.

Constrictive pericarditis is characterized by fibrosis and calcification of the pericardium that progressively impair the diastolic filling of the heart, causing heart failure. Uncommonly, pericardial constriction may be localized leading to a focal cystic mass formation that may compress nearby cardiac structures. We describe a unique case of a patient presenting with right heart failure due to idiopathic calcific constrictive pericarditis that was associated with a large pericardial cystic mass compressing the right ventricular free wall. This led to reduced cardiac output and possibly severe focal stenosis of the proximal right coronary artery that was resolved after pericardiectomy, the only definitive treatment for chronic progressive constrictive pericarditis.

Despite the impressive decline in mortality from atherosclerotic cardiovascular diseases (ASCVD), these diseases still account for a large proportion of the overall morbidity and mortality worldwide. A vast amount of research has demonstrated the key role played by circulating lipoproteins, and especially low-density lipoprotein (LDL), in the etiology of atherosclerosis, and numerous studies have proven the efficacy of interventions that lower the atherogenic lipoproteins in reducing morbidity and mortality from ASCVD. While previous guidelines placed an emphasis on the use HMG-CoA reductase inhibitors (statins) for the treatment of dyslipidemia, recent studies have shown that other LDL cholesterol lowering drugs, including ezetimibe and the PCSK9 inhibitors, can provide additional benefit when used in combination with (and in certain cases instead of) statins. These studies have also shown that blood LDL cholesterol levels lower than previously recommended targets provide additional benefit, without evidence of a threshold beyond which the benefit ceases and without excess adverse effects. The updated guidelines were formulated by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, the Israel Society of Internal Medicine, the Israeli Heart Association, the Israeli Neurology Association and the Israel Association of Family Medicine. They provide recommendations for revised risk stratification of patients, novel target goals, and the use of evidence-based treatment and follow-up strategies with reference to specific patient sub-groups.

Background Isolated tricuspid valve replacement (TVR) is considered high-risk surgery. We investigated our outcomes of TVR with the aim of identifying variables that may influence morbidity and mortality of isolated TVR compared with combined TVR and left-sided valve surgery. Methods Retrospective analysis of patients undergoing TVR surgery. The primary endpoint was long-term mortality. The association of postoperative outcomes with isolated compared with combined replacement was analyzed. The association between type of surgery and mortality over time was evaluated using Cox proportional hazards regression models to estimate the hazard ratio. Results Overall, 70 patients underwent TVR. Mean age was 61 ± 12 years and 74% (52 of 70) were women. About two thirds (61%) of the study population had a diagnosis of rheumatic heart disease and 8% (6 of 70) had previous infectious endocarditis. Atrial fibrillation was prevalent (86%, 60 of 70). Comorbidities were similar between groups. Tricuspid valve replacement combined with left-sided valvular surgery was performed in 37 patients (53%), and isolated replacement in 33 patients (47%). Previous cardiac surgery was common (40 patients, 57%). One-month survival rate was 94.3% (66 of 70). During a median follow-up period of 3.6 years, 12 patients (17%) died. The cumulative 5-year survival tended to be lower among patients with isolated TVR compared with patients having combined surgery. Conclusions We showed that TVR can be performed with good outcomes. Isolated TVR did not increase morbidity and mortality when patients are referred for surgery early, including after previous sternotomy. This finding should perhaps lead to a more aggressive approach toward patients requiring isolated replacement.

Recent guidelines recommend further reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk populations. The use of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) enables many patients to achieve profound reduction in LDL-C. However, in patients with low cholesterol, the commonly used Friedewald equation tends to underestimate LDL-C, which may result in undertreatment. We aimed to compare Friedewald LDL-C estimation with the more novel Martin/Hopkins method in PCSK9i-treated patients achieving low LDL-C.We investigated high-risk patients treated by PCSK9i in whom Friedewald LDL-C levels were 70 mg/dL and triglycerides ≤ 300 mg/dL. LDL-C was additionally assessed by the Martin/Hopkins method. The compatibility between estimations was evaluated using methods of concordance and reclassification between LDL-C categories ( 25, 25-40, 40-55, 55-70 mg/dL) and according to triglyceride strata.Mean age was 65 ± 10 years. The correlation coefficient between LDL-C estimations was r = 0.898. Martin/Hopkins reclassified 269 of the 608 patients (44%) to a higher LDL-C category, with 14% of the patients reaching LDL-C 70 mg/dL. Of the 390 patients achieving Friedewald LDL-C 55 mg/dL, 113 (29%) were estimated to have LDL-C ≥ 55 mg/dL by the Martin/Hopkins equation. The magnitude of discordance between LDL-C estimates was more pronounced in hypertriglyceridemic patients in whom LDL-C reclassification from 55 to ≥ 55 mg/dL was observed in 48%.In real-world practice of high-risk patients achieving low LDL-C under PCSK9i, Martin/Hopkins algorithm displayed significant proportion of LDL-C upward discordance compared to the Friedewald equation, particularly observed in patients with elevated triglycerides, identifying patients that may need treatment intensification.

Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein cholesterol (LDL-C), improving cardiovascular outcomes in clinical trials when added to statin therapy.As real-world evidence is lacking, we aimed to evaluate treatment and adherence patterns using PCSK9i in clinical practice.We investigated 1600 patients initiating PCSK9i between January 2016 and December 2019 in a large health maintenance organization. Treatment discontinuation was defined as a gap ≥60 days between last days' supply of one prescription and the start of the next. Re-initiation rates as well as proportion of days covered (PDC) over 1-year period and attainment of lipid goals under PCSK9i, were analyzed.Evolocumab 140 mg was initiated by 50.7%, alirocumab 75 mg by 29.5% and 150 mg by 19.8%. Cumulative discontinuation rates were 28.1% after 6-months and 49.9% after 3-years. Overall, 58% of the patients that discontinued therapy have re-initiated PCSK9i (31% after 3-months from discontinuation). Mean PDC over 1-year of therapy was 56% ± 29, with PDC ≥80% evident in 29%. Of those with established cardiovascular disease (n = 991), 55% achieved LDL-C70 mg/dL and 38% LDL-C55 mg/dL. Attainment rates were lower in patients with PDC80%, baseline LDL-C190 mg/dL and in those not treated with concurrent statin therapy.In real-world practice of patients treated by PCSK9i, high proportion of early treatment discontinuation was evident, with non-negligible re-initiation rates but overall low medication coverage over time. This have contributed to sub-optimal attainment of LDL-C treatment goals, particularly observed in patients with severe hypercholesterolemia, inadequate drug adherence, and those using PCSK9i as monotherapy.

The impact of revascularization of coronary chronic total occlusion (CTO) on survival is unknown. Several studies, which included subjects with varied coronary anatomy, suggested that CTO revascularization improved survival. However, the contribution of CTO revascularization to improved outcome is unclear since it was more commonly achieved in subjects with fewer co-morbidities and less extensive coronary disease.To study the association between CTO revascularization and survival in patients with uniform coronary anatomy consisting of isolated CTO of the right coronary artery (RCA).A registry of 16,832 coronary angiograms was analyzed. We identified 278 patients (1.7%) with isolated CTO of the RCA who did not have lesions within the left coronary artery for which revascularization was indicated. Survival of 52 patients (19%) who underwent successful percutaneous coronary intervention was compared to those who did not receive revascularization.Revascularized patients were younger (60.2 vs. 66.3 years, P = 0.001), had higher creatinine clearance (106 vs. 83 ml/min, P0.0001), and had fewer co-morbidities than those who did not receive revascularization. Lack of CTO revascularization was a univariable predictor of mortality (hazard ratio [HR] = 2.65, 95% confidence interval [95%CI] 1.06-6.4) over 4.3 ± 2.5 years of follow-up. On multivariable analysis, the only predictors of mortality were increased age (HR 1.04, 95%CI 1.01-1.07), reduced creatinine clearance (HR 1.02, 95%CI 1.01-1.03), and ejection fraction below 55% (HR 2.24, 95%CI 1.22-4.11).Among patients with isolated RCA CTO who underwent extended follow-up, revascularization was not an independent predictor of increased survival.

[Abstract] Aim. To investigate the characteristics long-term prognostic implications (up to ∼2.2 years) of atrial fibrillation (AF) compared to sinus rhythm (SR), between acute and chronic heart failure (HF) with reduced (HFrEF

Comprehensive data on severe hypertriglyceridemia (HTG) in the general population setting are limited and of importance due to the increase in metabolic risk factors and novel therapies under development.To investigate contributing causes and outcomes of severe to extreme HTG.Regional database retrospectively analyzed for subjects with severe HTG. Adverse outcomes were investigated in correlation to HTG severity, with follow-up initiating at first documentation of HTG1000 mg/dL.A total of 3091 subjects with severe (peak triglycerides 1000-1999 mg/dL; n = 2590), very severe (2000-2999 mg/dL; n = 369), and extreme (≥3000 mg/dL; n = 132) HTG were identified. Mean age was 48 ± 12 years; 73% males. Obesity (48%) and diabetes (62%) were main contributing factors. During follow-up (median 101 months), 4.7% subjects had pancreatitis, 4.7% myocardial infarction, and 6% stroke. Compared with severe HTG, the multivariate-adjusted hazard ratio for pancreatitis was 3.22 (95% confidence interval 2.21-4.70) for individuals with very severe HTG and 5.55 (3.53-8.71) for those with extreme HTG, P .0001. In contrast, the extent of HTG severity at these levels was not associated with worse cardiovascular outcomes or death. Most subjects (81%) achieved triglyceride levels500 mg/dL, associated with lower risk for developing pancreatitis but not myocardial infarction or stroke.Severity of HTG is closely related to cardiometabolic conditions, with a stepwise increase in the risk for pancreatitis, particularly if not attaining reduced triglyceride levels during the follow-up. In contrast, whereas mild-to-moderate HTG is a known established cardiovascular risk factor, very severe and extreme HTG may not further increase the risk for myocardial infarction, stroke, or mortality.

We examined 18,654 patients who underwent cardiac catheterization in a single center to clarify the association between catheterization indication, body mass index (BMI), and long-term survival over a mean follow-up of 81 months. Patients were grouped by indication for catheterization: (a) acute coronary syndromes (ACS), 7,426 patients; (b) coronary artery disease (CAD) evaluation in stable clinical presentation, 6,911 patients; and (c) primarily non-CAD cardiac evaluations, 4,317 patients. Compared with normal weight, overweight and obesity (but not morbid obesity) was associated with lower risk of long-term mortality. Underweight patients had the greatest risk of mortality. After multivariate adjustment, survival benefit of the overweight and obese was retained in the ACS group [hazard ratio 0.86, 95% confidence interval (0.77-0.96), p = 0.006 and 0.79, (0.68-0.91), p = 0.001, respectively] and in overweight patients in the stable presentation CAD group [0.83, (0.72-0.94), p = 0.005], whereas there was no survival benefit in any of the BMI categories in those catheterized primarily for non-CAD indications. Further analysis of matched cohorts showed similar patterns of survival benefit of the overweight/obese. In conclusion, among patients who underwent cardiac catheterization, an inverse association between BMI and long-term mortality was observed, with the lowest risk noted in the overweight and obese population; the obesity paradox was principally demonstrated in patients with ACS, and was eliminated after covariate adjustment in those catheterized primarily for non-CAD indications.

Background Familial hypercholesterolemia is characterized by markedly increased low-density lipoprotein cholesterol and risk for premature atherosclerotic cardiovascular disease. Models of care vary and reflect differing health policies and resources. The availability of electronic databases may enable better identification and assessment of familial hypercholesterolemia in the community. Methods A regional healthcare database was utilized to identify patients with a high probability of familial hypercholesterolemia, clinically defined by age-dependent-peak low-density lipoprotein cholesterol cutoffs and exclusion of secondary causes of severe hypercholesterolemia. Clinical characteristics, low-density lipoprotein cholesterol goal attainment, and treatment gaps were investigated. Results Probable familial hypercholesterolemia was diagnosed in 1932 of 685,314 individuals (1:355; median age 47 years). Atherosclerotic cardiovascular disease was present in 16.3% of adults (38% in males aged 50-74 years). Median peak low-density lipoprotein cholesterol was 264 mg/dl (interquartile range 252-288). Statins and/or ezetimibe were prescribed to 83% of patients and high-intensity statins to 53%, whereas prescriptions were filled in 57% and 40% cases respectively over the last six months, p 0.001. Treatment gaps were wider among ethnic minorities, younger individuals, and those without atherosclerotic cardiovascular disease. Low-density lipoprotein cholesterol 100 mg/dl was attained in 10.1% overall and 28.7% of those with atherosclerotic cardiovascular disease. Predictors of low-density lipoprotein cholesterol goal attainment included recent issue of high-intensity statins, presence of atherosclerotic cardiovascular disease, diabetes, older age and lack of smoking. Conclusions The population with high probability for familial hypercholesterolemia was characterized by low attainment of low-density lipoprotein cholesterol treatment goals despite high prescription rates of lipid-lowering medications. Low utilization of intensified therapies, non-adherence, and ethnic disparities were contributing factors. These findings emphasize the need to improve awareness and quality of care of familial hypercholesterolemia in the community.

Background Chronic kidney disease and anemia often coexist and may accompany diabetes; all 3 conditions are associated with worse cardiovascular outcomes. This study investigated the prognostic implications of anemia and chronic kidney disease for mortality among patients undergoing coronary artery-bypass grafting surgery and examined whether outcomes are related to the presence of diabetes. Methods This retrospective study included 1180 patients undergoing coronary artery-bypass grafting. Long-term mortality (mean follow-up, 8.6 ± 4.2 years) was examined in relation to preoperative anemia, chronic kidney disease, and diabetes. Prognostic interplay of the 3 risk factors was evaluated. Results Chronic kidney disease, anemia, and diabetes (20%, 25%, and 43% of patients, respectively), were independent risk predictors for mortality. Compared with patients with neither chronic kidney disease nor anemia, the adjusted hazard ratios (HRs) for mortality were 1.87 (95% confidence interval [CI], 1.35 to 2.59) in chronic kidney disease only, 1.75 (95% CI, 1.30 to 2.35) in anemia only, and 2.69 (95% CI, 1.91 to 3.78) in patients with both conditions. The pattern of association of chronic kidney disease and anemia with mortality was similar in patients with and without diabetes. However, mortality risk was higher in patients with diabetes in each risk category—neither chronic kidney disease nor anemia: HR, 1.69 (95% CI, 1.20 to 2.39) vs HR, 1 (reference); chronic kidney disease only: HR, 2.68 (95% CI, 1.59 to 4.52) vs HR, 2.10 (95% CI, 1.38 to 3.20); anemia only: HR, 2.73 (95% CI, 1.83 to 4.07) vs HR, 1.94 (95% CI, 1.23 to 3.08); and both chronic kidney disease and anemia: HR, 4.44 (95% CI, 2.88 to 6.85) vs HR, 2.72 (95% CI, 1.58 to 4.69). Conclusions In patients undergoing coronary artery-bypass grafting, anemia and chronic kidney disease have significant prognostic implications for long-term mortality. Their effect on mortality was cumulatively associated with adverse impacts of diabetes.

Background A risk score for secondary prevention after myocardial infarction (TRS2P) was recently developed from the TRA2°P-TIMI50 trial based on 9 established clinical factors [age≥75, hypertension, diabetes, smoking, kidney dysfunction, peripheral artery disease, heart failure, prior stroke and prior coronary artery-bypass surgery (CABG)], classifying the risk for major adverse cardiovascular events (MACE). We aimed to evaluate the performance of TRS2P for predicting long-term outcomes in real-world patients presenting for coronary angiography. Methods Retrospective analysis of 13,593 patients that were referred to angiography for the assessment or treatment of coronary artery disease between 2000–2015 in a single center. Risk stratification for 10-year MACE (myocardial infarction, ischemic stroke or all-cause death) was performed using the TRS2P score, divided into 6 categories (0 to ≥5 points), and in relation to the presenting coronary syndrome. Results All clinical variables, except of prior CABG, were independent risk predictors. The annualized incidence rate of MACE increased in a graded manner with increasing TRS2P score, ranging from 1.65 to 16.6 per 100 person-years (ptrend Cumulative 10-year incidence of MACE Conclusions The use of TRS2P, a simple risk score based on routinely collected variables, enables risk stratification in patients undergoing coronary angiography. Its predictive value was demonstrated in real-world setting with long-term follow-up, and irrespective of the acuity of coronary presentation. Acknowledgement/Funding None

Background A risk score for secondary prevention after myocardial infarction (Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention [TRS2P]), based on 9 established clinical factors, was recently developed from the TRA 2°P‐ TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events) trial. We aimed to evaluate the performance of TRS 2P for predicting long‐term outcomes in real‐world patients presenting for coronary angiography. Methods and Results A retrospective analysis of 13 593 patients referred to angiography for the assessment or treatment of coronary disease was performed. Risk stratification for 10‐year major adverse cardiovascular events was performed using the TRS 2P, divided into 6 categories (0 to ≥5 points), and in relation to the presenting coronary syndrome. All clinical variables, except prior coronary artery bypass grafting, were independent risk predictors. The annualized incidence rate of major adverse cardiovascular events increased in a graded manner with increasing TRS 2P, ranging from 1.65 to 16.6 per 100 person‐years ( P trend TRS 2P showed reasonable discrimination with C‐statistics of 0.693 for major adverse cardiovascular events and 0.758 for mortality. The graded relationship between the risk score and event rates was observed in both patients presenting with acute and nonacute coronary syndromes. Conclusions The use of TRS 2P, a simple risk score based on routinely collected variables, enables risk stratification in patients undergoing coronary angiography. Its predictive value was demonstrated in a real‐world setting with long‐term follow‐up and regardless of the acuity of coronary presentation.