[DIAGNOSIS AND TREATMENT OF ELEVATED LIPOPROTEIN(A) IN ISRAEL: CONSENSUS STATEMENT FROM THE ISRAEL SOCIETY FOR RESEARCH, PREVENTION AND TREATMENT OF ATHEROSCLEROSIS AND ISRAEL SOCIETY FOR CLINICAL LABORATORY SCIENCES].

INTRODUCTION: Lipoprotein(a) [Lp(a)] is composed of 2 major protein components, a low-density lipoprotein (LDL) cholesterol-like particle containing apolipoprotein B (apo B) that is covalently bound to apolipoprotein(a). Its level is predominantly genetically determined, and it is estimated that 20% to 25% of the population have Lp(a) levels that are associated with increased cardiovascular risk. Elevated Lp(a) is related to increased vascular inflammation, calcification, atherogenesis and thrombosis, and is considered an independent and potentially causal risk factor for atherosclerotic cardiovascular diseases and calcified aortic valve stenosis. Recent data demonstrate that Lp(a) testing has the potential to reclassify patients' risk and improve cardiovascular risk prediction, and therefore could inform clinical decision-making regarding risk management. Statins and ezetimibe are ineffective in lowering Lp(a) levels, whereas proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have a modest effect on Lp(a) reduction. Nevertheless, RNA interference-based therapies with potent Lp(a)-lowering effects are in advanced stages of development, and clinical trials are underway to confirm their benefit in reducing cardiovascular events. This scientific consensus document was developed by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, and the Israeli Society for Clinical Laboratory Sciences, in order to create uniformity in Lp(a) measurement methods, indications for testing and reporting of the results, aiming to improve the diagnosis and management of elevated Lp(a) in clinical practice.

CHA2DS2-VASc Score as a Predictor of Adverse Outcomes after Ischemic Stroke in Patients without Atrial Fibrillation.

BACKGROUND: Ischemic stroke is associated with increased risk of morbidity and mortality in future vascular events. OBJECTIVES: To investigate whether CHA2DS2-VASc scores aid in risk stratification of middle-aged patients without atrial fibrillation (AF) experiencing ischemic stroke. METHODS: We analyzed data of 2628 patients, aged 40-65 years with no known AF who presented with acute ischemic stroke between January 2020 and February 2022. We explored the association between CHA2DS2-VASc scores categorized by subgroups (score 2-3, 4-5, or 6-7) with major adverse cardiac and cerebrovascular events (MACCE) including recurrent stroke, myocardial infarction, coronary revascularization, or all-cause death during a median follow-up of 19.9 months. RESULTS: Mean age was 57 years (30% women); half were defined as low socioeconomic status. Co-morbidities included hypertension, diabetes, obesity, and smoking in 40-60% of the patients. The incidence rate of MACCE per 100 person-years was 6.7, 12.2, and 21.2 in those with score 2-3, 4-5, and 6-7, respectively. In a multivariate cox regression model, compared to patients with score 2-3 (reference group), those with score 4-5 and 6-7 had an adjusted hazard ratio (95% confidence interval [95%CI]) for MACCE of 1.74 (95%CI 1.41-2.14) and 2.87 (95%CI 2.10-3.93), respectively. The discriminative capacity of CHA2DS2-VASc score for overall MACCE was modest (area under curve 0.63; 95%CI 0.60-0.66), although better for myocardial infarction 0.69 (95% CI 0.61-0.77). CONCLUSIONS: CHA2DS2-VASc score may predict future MACCE in middle-aged patients with ischemic stroke and no history of AF.

Outcome of transcatheter aortic valve replacement in Israeli Jews and Arabs.

Background: Ethnic minorities may face disparities in access to health care and clinical outcomes. Transcatheter aortic valve replacement (TAVR) has an established role in treatment of patients with severe symptomatic aortic stenosis, however outcome of these procedures among different demographics within the multi-ethnic Israeli society is unknown. We sought to compare mortality following TAVR between Jewish and Arab patients in Israel. Methods: A prospective single-center TAVR registry in northern Israel was analyzed. We compared post-procedural survival among Arab and Jewish patients who underwent TAVR, presenting the estimated hazard ratio (HR) using Cox regression. Results: Of 923 subjects who underwent TAVR between 2010-2021, 172 (19%) were Arab and 751 (81%) were Jewish. The Arab patient population was younger (mean 77 vs. 81 years, P<0.001), had lower prevalence of coronary artery disease (34%, vs. 43%, P=0.02), hypertension (80% vs. 88%, P<0.01) and calculated procedural mortality (EuroScore II: mean 4.6 vs. 4.9, P=0.02), and higher percentage of females (65% vs. 53%, P=0.01), body mass index (mean 30 vs. 28, P<0.001) and creatinine clearance (mean 67 vs. 59 mL/min, P<0.001). Arab patients had similar post-procedural mortality compared to Jewish patients [7-day mortality: adjusted HR 1.51, 95% confidence interval (CI): 0.39-5.77, P=0.55; 30-day mortality: adjusted HR 1.79, 95% CI: 0.62-5.18, P=0.29; 1-year mortality: adjusted HR 1.24, 95% CI: 0.72-2.12, P=0.43]. Conclusions: Arab patients undergoing TAVR were younger and had lower predicted mortality than Jewish counterparts, however, these characteristics did not translate into improved post-procedural survival.

Cardiorespiratory Fitness and Risk of Cardiovascular Events and Mortality in Middle Age Patients without Known Cardiovascular Disease.

BACKGROUND: Low cardiorespiratory fitness is an established risk predictor for chronic non-communicable diseases. We aimed to investigate the prognostic significance of fitness level on the risk of major adverse cardiac events (MACE, the composite of myocardial infarction, stroke, or all-cause death), in a contemporary cohort of middle-aged subjects without cardiovascular disease. METHODS: Retrospective analysis of patients aged 40-60 years without a history of cardiovascular disease. Degree of fitness was determined according to a graded, maximal treadmill exercise stress testing (EST) time achieved, classified into age- and sex-specific quintiles (Q), and categorized as low (Q1), moderate (Q2-Q4) or high (Q5) fitness groups. A multivariable Cox proportional hazard regression model was used to assess the association of fitness level with the risk of MACE. RESULTS: A total of 6836 patients were included, of which 44.5% were women, and the mean age was 52 years. Overall, 289 MACE events occurred during a median follow-up of 7 years. Level of fitness was inversely associated with the presence of cardiovascular risk factors. The multivariable adjusted hazard ratio (95% confidence interval) for MACE was 1.65 (1.12-2.44) and 2.17 (1.40-3.38) in those at moderate and low fitness levels, compared to the high-fitness group (reference), respectively. For each decrease of one metabolic equivalent (MET) unit achieved at peak exercise, the relative risk for MACE increased by 18%. The association between low fitness and MACE was not modified by other risk factors (P-for-interaction non-significant). CONCLUSIONS: Low fitness level, as captured by a maximal treadmill EST, is an independent risk predictor for MACE among middle-age individuals without known cardiovascular disease. The association of low fitness with high burden of cardiometabolic risk factors highlight the importance of lifestyle intervention in this patient population.

Extreme Hypercholesterolemia Following a Ketogenic Diet: Exaggerated Response to an Increasingly Popular Diet.

A high-fat, very low-carbohydrate diet, often named the "ketogenic diet," is gaining popularity, particularly among patients with obesity and metabolic syndrome seeking rapid weight loss and improvement in glycemic control. A favorable reduction in triglycerides and an increase in high-density lipoprotein-cholesterol levels is often observed in the ketogenic diet. However, people vary significantly in their low-density lipoprotein-cholesterol (LDL-C) response to the dietary change. Here, we present the case of a 38-year-old normal-weight male with average cholesterol levels showing an extreme fourfold elevation in LDL-C levels, reaching 496 mg/dL after initiating a ketogenic diet. We highlight that a dramatic elevation in LDL-C may manifest following a ketogenic diet in normal-weight people without known genetic dyslipidemias before the dietary change; therefore, increased awareness and close monitoring of blood lipid profile is essential for all individuals following a ketogenic diet. We further discuss the potential mechanisms for the "lean mass hyper-responders" phenotype which has been recently gaining recognition, and suggest that these patients may benefit from ezetimibe therapy, decreasing the absorption of intestinal cholesterol to the liver.

Guideline-Directed Low-Density Lipoprotein Cholesterol Management After Acute Ischemic Stroke: Findings from a National Health Care Service.

Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets early after ischemic stroke are limited. We extracted data from the largest healthcare provider in Israel on patients hospitalized with acute ischemic stroke between January 2020 and February 2022. Included were 3,027 patients surviving ≥1 year after stroke, with documented LDL-C levels and lipid-lowering medications at 2 time periods (0 to 3 months and 6 to 12 months after discharge). Participants were classified according to preexisting stroke and/or coronary artery disease. The use of combination lipid-lowering therapy (ezetimibe and/or proprotein convertase subtilisin/kexin type 9 [monoclonal antibodies] inhibitor plus statin) in the study population increased between the 2 timepoints from 3.6% to 5.1%, reaching 10.5% in those with previous coronary artery disease and stroke. LDL-C levels <70 and <55 mg/100 ml were attained by 42.3% and 22.9% of patients early after hospitalization, and in 49.5% and 27.1% during 6 to 12 months after hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in patients treated with combination lipid-lowering therapies and in those with preexisting cardiovascular disease. In conclusion, despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies after hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

Heart Failure Therapies following Acute Coronary Syndromes with Reduced Ejection Fraction: Data from the ACSIS Survey.

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.

Remnant cholesterol and risk of myocardial infarction in patients with coronary artery disease undergoing revascularization.

BACKGROUND: Despite substantial reduction in low-density lipoprotein cholesterol (LDL-C), patients develop recurrent cardiovascular events. Remnant cholesterol (RC), the cholesterol content of triglyceride-rich lipoproteins, is a potential contributor to this residual risk. OBJECTIVES: To investigate the association between RC and risk for myocardial infarction (MI) in patients with coronary artery disease, and examine whether the predictive value of RC is retained beyond non-high-density lipoprotein cholesterol (non-HDL-C). METHODS: Data on 9451 patients undergoing coronary revascularization in a single center. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus LDL-C (estimated using Martin-Hopkins equation). Cox-regression models were used to estimate the association between RC and risk for MI. Discordance analyses were performed to examine the correlation between RC and non-HDL-C (or LDL-C) in relation to MI risk. RESULTS: Mean age was 65±11 years; 67% presented with acute coronary syndrome. During median follow-up of 9.6 years, 1690 patients developed MI. After multivariable adjustment including lipid-lowering therapies and non-HDL-C, RC was associated with higher MI risk: hazard ratio (95% confidence interval): 1.36 (1.20-1.56) and 1.58 (1.35-1.85) in those with RC levels ≥75th (32.6 mg/dL) and ≥90th (41.8 mg/dL) percentile, compared to RC <50th percentile (25.5 mg/dL). When RC and non-HDL-C (or LDL-C) levels were discordant, the level of RC better reflected the risk for MI. CONCLUSIONS: Elevated RC is a risk factor for MI independent of lipid-lowering therapies and non-HDL-C, providing further support that RC may serve as a residual cardiovascular risk marker and potential treatment target in patients with coronary artery disease.

Extreme lipoprotein(a) in clinical practice: A cross sectional study.

Introduction: Measurement of lipoprotein(a) [Lp(a)] is recommended once in a lifetime to identify individuals at high risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to analyze the clinical features of patients with extreme Lp(a). Methods: Cross-sectional, case-control study of a single healthcare organization between 2015 and 2021. Individuals with extreme Lp(a) > 430 nmol/L (53 of 3900 tested patients) were compared to age- and sex-matched controls with normal range Lp(a). Results: Mean patient age was 58 ± 14 years (49% women). Myocardial infarction (47.2% vs. 18.9%), coronary artery disease (CAD) (62.3% vs. 28.3%), and peripheral artery disease (PAD) or stroke (22.6% vs. 11.3%) were more prevalent in patients with extreme than normal range Lp(a). The adjusted odds ratio [95% confidence interval (CI)] associated with extreme compared to normal range Lp(a) was 2.50 (1.20-5.21) for myocardial infarction, 2.20 (1.20-4.05) for CAD, and 2.75 (0.88-8.64) for PAD or stroke. A high-intensity statin plus ezetimibe combination was issued by 33% and 20% of CAD patients with extreme and normal range Lp(a), respectively. In patients with CAD, low density lipoprotein cholesterol (LDL-C) <55 mg/dL was achieved in 36% of those with extreme Lp(a) and 47% of those with normal range Lp(a). Conclusions: Extremely elevated Lp(a) levels are associated with an approximately 2.5-fold increased risk of ASCVD compared with normal range Lp(a) levels. Although lipid-lowering treatment is more intense in CAD patients with extreme Lp(a), combination therapies are underused, and attainment rates of LDL-C goals are suboptimal.

The interplay among body weight, blood pressure, and cardiorespiratory fitness in predicting atrial fibrillation.

BACKGROUND: 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. METHODS: 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/m2), hypertension (blood pressure ≥140/90 mmHg or history of hypertension), or low CRF (exercise capacity <8 metabolic equivalents). Cox proportional hazards models were used to evaluate the individual and combined association between the 3 risk indicators and AF. RESULTS: The 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. CONCLUSIONS: 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.

The Impact of Smoking Status 1 Year After ST-Segment Elevation Myocardial Infarction on Cardiovascular Events and Mortality in Patients Aged ≤60 Years.

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.

Heart Rate Response to Exercise and Recovery: INDEPENDENT PROGNOSTIC MEASURES IN PATIENTS WITHOUT KNOWN MAJOR CARDIOVASCULAR DISEASE.

PURPOSE: 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. METHODS: 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 abnormal <42 beats) and chronotropic index (CI; defined abnormal <80%, 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. RESULTS: The HRR2 <42 beats and CI <80% 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). CONCLUSIONS: 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.

Blood pressure measurements during treadmill exercise testing and the risk for the future development of atrial fibrillation.

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 CHA2DS2VASc scores (3.26 for a Score=0 to 19.78 for scores ≥6). In a multivariate analysis, adjusting for risk score components and exercise capacity, systolic BP measurements taken at rest (≥130 vs. ≤110 mmHg), peak exercise (>170 vs. ≤150 mmHg), and recovery (>150 vs. ≤130 mmHg) were associated with an increased risk for AF: the hazard ratios (HRs) were 1.56 (95% CI, 1.30-1.87), 1.21 (1.01-1.45), and 1.33 (1.10-1.62), respectively. Similarly, diastolic BP measurements taken at rest (≥90 vs. <80 mmHg), peak exercise (≥100 vs. <90 mmHg), and recovery (>90 vs. ≤80 mmHg) were associated with an increased risk for AF: the HRs were 1.80 (1.36-2.38), 2.08 (1.28-3.37), and 1.56 (0.81-3.02), respectively. The association of exercise BP with AF was further observed when the BPs were analyzed as continuous variables and in subjects without a baseline diagnosis of hypertension. In conclusion, systolic and diastolic BP taken at the rest, peak exercise and recovery phases of EST may provide independent predictive information regarding future risk for developing AF.

Transbrachial Secondary Vascular Access in Transcatheter Aortic Valve Replacement Procedures: A Single-Centre Retrospective Analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: Transbrachial secondary access in TAVR procedures was feasible and enabled percutaneous vascular repair in cases of femoral artery injury.

Biological or mechanical mitral valve replacement in patients 50-70 years of age-a propensity-adjusted analysis.

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 <65 years of age.

Lymphopenia and mortality among patients undergoing coronary angiography: Long-term follow-up study.

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.