Events In High-risk Patients Research Articles

Red cell distribution width as a predictor of cardiovascular events in high-risk patients with statin intolerance: post-hoc analysis of the CLEAR Outcomes trial

Abstract Background Despite optimal lipid-lowering therapy there is up to 70% residual risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events, motivating further testing of alternative risk factors and disease pathways. Red cell distribution width (RDW) is a simple and reproducible marker of heterogeneity of cell size in the peripheral blood. High RDW is associated with an increased risk of ASCVD and death, independent of established risk factors. Recent data suggest no significant impact of PCSK9 inhibitors on hsCRP or RDW. In CLEAR Outcomes, baseline hsCRP predicted risk for future cardiovascular (CV) events and death more strongly than elevated LDL-C. It has been shown that bempedoic acid (BA) reduces hsCRP, but its effects on RDW are unknown. Purpose To analyze the effect of BA on a 4-component composite of incident myocardial infarction, stroke, coronary revascularization, or cardiovascular death (MACE-4) and for CV death by baseline RDW, and to confirm the association of increased RDW with elevated risk of MACE. Methods A total of 13,970 individuals with statin intolerance, with or at high risk for ASCVD, were randomized in the multinational CLEAR Outcomes trial with a median follow up of 3.4 years. Compared to placebo, BA reduced mean LDL-C by 21% and median hsCRP by 22% at 6 months. Quartiles of increasing baseline RDW were assessed as predictors of future adverse events after adjustment for traditional risk factors, hsCRP, and randomized treatment assignment. Results Compared to placebo, BA reduced mean RDW by 0.28% at 6 months and 0.13% at 36 months (p<0.0001). There was a weak positive correlation between hsCRP and RDW at baseline (Figure 1). In the placebo group, higher baseline RDW was associated with an increase in the likelihood of MACE-4 and CV death, and the hazard ratios (HR) associated with a 1% increase in RDW after adjusting for covariates and hsCRP were 1.06 (95% CI 1.02-1.11) and 1.22 (1.15-1.29), respectively. When grouped by quartiles of baseline RDW, compared with a reference group with lowest RDW (<13.7%), there was a notable increase in the risk of MACE-4 and CV death among the higher quartiles in the placebo group (Table 1). Those in the 4th quartile demonstrated a 3-fold increase in the risk of CV death (HR, 3.03, 2.00-4.60). The adjusted HRs (95% CI) for BA vs placebo for MACE-4 were generally lower in individuals with elevated baseline RDW than in those in the first quartile [Q1: RDW≤13.7%; 0.96 (0.79-1.17), Q2: RDW 13.7%-14.4%; 0.81 (0.67-0.97), Q3: RDW 14.4%-15.2%; 0.90 (0.75-1.09), and Q4: RDW>15.2%; 0.84 (0.7-1.01)]. Conclusions In a large randomized controlled clinical trial setting, we confirmed an association between elevated RDW and MACE-4. Compared with placebo, BA demonstrated efficacy in reducing CV risk in patients with moderately increased RDW.Figure 1.Correlation of hsCRP and RDWTable 1.Risk of Outcome by RDW Quartile

Association between epidermal growth factor receptor-tyrosine kinase inhibitors and venous thromboembolism among older patients with advanced non-small cell lung cancer.

Venous thromboembolism (VTE) risk is higher among patients with non-small cell lung cancer (NSCLC) and specific subgroups, including the elderly, but little is known about the VTE risk of different generations of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and whether the risk differs by demographic characteristics. This study aims to compare the risk of VTE (deep venous thromboembolism [DVT]; pulmonary embolism [PE]) between a third-generation EGFR-TKI and first/second-generation EGFR-TKIs and stratify VTE risk by sex, age, and race/ethnicity in third-generation EGFR-TKI users. Via the 2006-2019 Surveillance, Epidemiology, and End Results-Medicare database, this retrospective cohort study included older patients (aged ≥65 years) with advanced NSCLC who initiated on a third-generation EGFR-TKI (n=493) and first/second-generation EGFR-TKIs (n=1036). We estimated the hazard ratio (HR) and its 95% confidence interval (95% CI) with the Cox proportional hazards model. A third-generation EGFR-TKI had a significantly higher VTE risk than first/second-generation EGFR-TKIs (HR, 1.26 [95% CI, 1.01-1.57]; p=.037), with an elevated risk in males (HR, 2.16 [95% CI, 1.47-3.19]; p<.001), patients aged ≥75 years (HR, 1.38 [95% CI, 1.04-1.83]; p=.026), and non-Hispanic Whites (HR, 1.46 [95% CI, 1.10-1.95]; p=.010). Males consistently showed a significantly higher risk of DVT (HR, 2.49 [95% CI, 1.29-4.80]; p=.007) and PE (HR, 2.00 [95% CI, 1.29-3.11]; p=.002). A significantly higher risk of DVT (HR, 1.54 [95% CI, 1.00-2.37]; p=.050) and PE (HR, 1.47 [95% CI, 1.06-2.05]; p=.021) was shown in patients aged ≥75 years and non-Hispanic Whites, respectively. Among third-generation EGFR-TKI users, non-Hispanic Whites had a significantly higher risk of VTE (HR, 2.04 [95% CI, 1.03-4.02]; p=.041) and PE (HR, 2.88 [95% CI, 1.24-6.70]; p=.014) than non-Hispanic Asian/Pacific Islanders. Close monitoring of VTE events in high-risk patients is essential to promote early diagnosis and treatment.

Applicability of Percutaneous Occlusion with Double Disc Prosthesis for Correction of Patent Foramen Ovale

Objective: To discuss the applicability of percutaneous occlusion with a double-disk prosthesis to correct patent foramen ovale. Methodology: Integrative review of the literature carried out in the Virtual Health Library (VHL), Google Scholar and PubMed databases, using the Health Sciences (DeCS) descriptors: “Prosthesis design”, “Patent foramen ovale” and “Cardiac catheterization ” combined with each other by the Boolean operator AND. Results: Patent foramen ovale (PFO) is a congenital condition characterized by non-healing of the foramen ovale after birth, which can lead to complications such as paradoxical embolism and cerebrovascular accidents. Percutaneous occlusion rates with double-disc prostheses have accompanied this increase in PFO detection, while the technique, which involves inserting a double-disc device into the foramen ovale to close it, has proven effective in preventing embolic events in patients with a history of cryptogenic stroke or other PFO-related manifestations. The approach of percutaneous occlusion with a double-disk prosthesis for PFO correction is, therefore, a valuable tool in the therapeutic arsenal to reduce the risk of embolic events in high-risk patients. Conclusion: Percutaneous occlusion with a double disc prosthesis is an effective approach to preventing embolic events in patients with patent foramen ovale. Its growth reflects technological advances and understanding of the risks of FOP.

#1584 Development and validation of risk prediction models according to different clinical settings of IgA nephropathy: nationwide multicenter cohort study

Abstract Background and Aims IgA nephropathy (IgAN) is the most common glomerulonephritis with a high risk of progression to end-stage renal disease (ESRD). Because machine learning models developed for research have limited use in clinical settings, this study developed and validated prediction models for IgAN according to different clinical settings. Method In this study, we analyzed data from 1,174 patients in the Japanese Nationwide Retrospective Cohort Study in IgAN, focusing on a 10-year observation period. We defined the derivation data from January 2002 to April 2004, and temporal validation data from May 2004 to December 2004. The composite renal outcome was defined as a 1.5-fold increase in creatinine or progression to ESRD. We developed and evaluated the three prediction models according to the different clinical settings: the primary care model for general physicians in primary care settings, the tertiary care model for specialists in tertiary care hospitals, and the research institute model, a machine learning-based approach for academic research institute settings. Results After excluding 82 patients for missing data, 114 and 14 patients experienced the composite renal outcome in the derivation (n = 874) and validation (n = 218) cohorts, respectively. The primary care model identified three variables—eGFR &amp;lt;45 mL/min/1.73 m², proteinuria ≥0.5 g/day, and non-use of corticosteroids—as significant predictors (C-statistic: 0.796; 95% CI: 0.686-0.895). The tertiary care model composed of three variables including glomerular number, histological severity and tubular/interstitial severity showed a slightly higher C-statistic (0.807; 95% CI: 0.713-0.886). When stratifying patients into risk groups, the primary care model showed a higher incidence of composite renal events in high-risk patients, and the tertiary care model effectively discriminated outcomes in all groups. The research institute model, which included 38 variables including proteinuria level, hypertension, eGFR, and non-use of corticosteroids as key predictors, showed comparable performance (C-statistic: 0.808; 95% CI: 0.689-0.886). Conclusion The primary care and tertiary care models provide simple yet effective predictive tools, competitive with the machine learning-based research institution model. These models are critical for predicting renal outcomes in patients with IgA nephropathy and for patient management according to different clinical settings.

The Efficacy and Safety of Sodium-Glucose Co-transporter2 (SGLT2) Inhibitors in Real-World Clinical Practice: Potential Cautionary Use in Elderly Patients with Type2 Diabetes (T2D).

Sodium-glucose co-transporter2 (SGLT2) inhibitors have shown safe and therapeutic efficacy in randomized controlled trials (RCT) to reduce adverse cardiorenal events in high-risk patients with type2 diabetes (T2D). In this study, we investigated the efficacy and safety of SGLT2 intervention in patients with T2D in a real-world clinical practice to confirm the validity of the RCT results. As a retrospective study, we evaluated medical records from 596 patients with T2D treated with SGLT2 inhibitors (dapagliflozin or empagliflozin) in addition to their prior drug regimen to improve glucose control between 2015 and 2019 in the Endocrinology Department at Chungbuk National University Hospital. No control arm was evaluated to compare the effects of adding SGLT inhibitors to the pre-existing regimen. The primary objective was the measurement of glycated hemoglobin (HbA1c) from each individual patient over a 36-month period at 6-month intervals. The secondary parameters were the measurement of fasting plasma glucose (FPG) and body weight (Bwt) changes, as well as the monitoring of adverse events (AEs) and determining the reasons for drug discontinuation. HbA1c levels were reduced at each of the time points throughout the 36-month period and were significantly reduced by 12.5% (P < 0.01) from time0 (8.8 ± 1.3%) to 36months (7.7 ± 1.0%). FPG levels [from basal (180 ± 60mg/dL) to 36months (138 ± 38mg/dL)] and Bwt [from basal (74 ± 15kg) to 36months (72 ± 15kg)] were also significantly reduced (P < 0.01) for both measurements in the SGLT2 inhibitor add-on group. Similar to HbA1c profile, the FPG and Bwt were measured at a consistently lower level at 6months until the end of the study. The most common AEs were hypoglycemia (n = 57), genitourinary infection (GUI) (n = 31), and polyuria (n = 28). In the elderly population (≥ 75years old), AEs (31%) were generally more prevalent (P < 0.001) than those (21%) in the adult (< 75years old) patients. Over the study period, 211 (35%) patients either dropped or completely discontinued the use of the SGLT2 inhibitor, and the elderly patients tended to have a higher discontinuation rate (52%; P = 0.005) than the adults (33%). In this study, we demonstrated that SGLT2 inhibitors are an effective and durable hypoglycemic agent to control blood glucose levels with reduced maintenance of Bwt, but their use in the elderly (≥ 75years old) patients with T2D may warrant some additional caution due to increased probability of AEs and discontinuation of drug use.

Long-term lipoprotein apheresis reduces cardiovascular events in high-risk patients with isolated lipoprotein(a) elevation

Elevated lipoprotein(a) (Lp(a)) is an established risk factor for cardiovascular disease (CVD). To date, the only approved treatment to lower Lp(a) is lipoprotein apheresis (LA). Previous studies have demonstrated that LA is effective in reducing cardiovascular (CV) risk in patients with elevated low-density lipoprotein cholesterol (LDL-C) and/or Lp(a). Here we report our long-term experience with LA and its effectiveness in reducing CVD events in patients with elevated Lp(a). This retrospective open-label, single-center study included 25 individuals with Lp(a) elevation >60 mg/dL and LDL-C < 2.59 mmol/L who had indication for LA. The primary endpoint of this study was the incidence of any CV event (determined by medical records) after initiation of LA. Mean LA treatment duration was 7.1 years (min-max: 1-19 years). Median Lp(a) was reduced from 95.0 to 31.1 mg/dL after LA (-67.3 %, p < 0.0001). Mean LDL-C was reduced from 1.85 to 0.76 mmol/L after LA (-58.9 %, p < 0.0001). Prior LA, 81 CV events occurred in total (0.87 events/patient/year). During LA, 49 CV events occurred in total (0.24 events/patient/year; -0.63, p = 0.001). Yearly major adverse cardiac event (MACE) rate was reduced from 0.34 to 0.006 (-0.33, p = 0.0002). Similar results were obtained when considering only individuals with baseline LDL-C below 1.42 mmol/L. In this observational study of a heterogeneous CV high-risk cohort with elevated Lp(a), LA reduced Lp(a) levels and was paralleled by a decrease in CV events and MACE. We recommend LA for patients with high Lp(a) who still have CV events despite optimal lipid-lowering medication and lifestyle changes.

Comparison of blood loss between intra-articular microporous polysaccharide hemospheres powder and tranexamic acid following primary total knee arthroplasty

Total knee arthroplasty (TKA) is associated with substantial blood loss and tranexamic acid (TXA) effectively reduces postoperative bleeding. Although it is known that there is no difference between intravenous or intra-articular (IA) injection, the general interest is directed towards topical hemostatic agents regarding thromboembolic events in high-risk patients. This study aimed to compare the blood conservation effects of IA MPH powder and TXA in patients undergoing primary TKA. We retrospectively analyzed 103 patients who underwent primary TKA between June 2020 and December 2021. MPH powder was applied to the IA space before capsule closure (MPH group, n = 51). TXA (3 g) was injected via the drain after wound closure (TXA group, n = 52). All patients underwent drain clamping for three postoperative hours. The primary outcome was the drain output, and the secondary outcomes were the postoperative hemoglobin (Hb) levels during the hospitalization period and the perioperative blood transfusion rates. An independent Student’s t-test was used to determine differences between the two groups. The drain output in the first 24 h after surgery was significantly higher in the MPH group than in the TXA group. The postoperative Hb levels were significantly lower in the MPH group than in the TXA group. In patients with simultaneous bilateral TKA, there was a significant difference in the blood transfusion volumes and the rates between groups. It is considered that IA MPH powder cannot replace IA TXA because of an inferior efficacy in reducing blood loss and maintaining postoperative Hb levels in the early postoperative period after primary TKA. Moreover, in the case of simultaneous bilateral TKA, we do not recommend the use of IA MPH powder because it was notably less effective in the field of transfusion volume and rate.

GLP-1 in patients with myocardial infarction complicated by cardiogenic shock-an IABP-SHOCK II-substudy.

Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted in response to nutritional and inflammatory stimuli. Elevated GLP-1 levels predict adverse outcome in patients with acute myocardial infarction or sepsis. GLP-1 holds cardioprotective effects and GLP-1 receptor agonists reduce cardiovascular events in high-risk patients with diabetes. In this study, we aimed to investigate the capacity of GLP-1 to predict outcome in patients with cardiogenic shock (CS) complicating myocardial infarction. Circulating GLP-1 levels were serially assessed in 172 individuals during index PCI and day 2 in a prospectively planned biomarker substudy of the IABP-SHOCK II trial. All-cause mortality at short- (30days), intermediate- (1year), and long-term (6years) follow-up was used for outcome assessment. Patients with fatal short-term outcome (n = 70) exhibited higher GLP-1 levels [86 (interquartile range 45-130) pM] at ICU admission in comparison to patients with 30-day survival [48 (interquartile range 33-78) pM; p < 0.001] (n = 102). Repeated measures ANOVA revealed a significant interaction of GLP-1 dynamics from baseline to day 2 between survivors and non-survivors (p = 0.04). GLP-1 levels above vs. below the median proved to be predictive for short- [hazard ratio (HR) 2.43; 95% confidence interval (CI) 1.50-3.94; p < 0.001], intermediate- [HR 2.46; 95% CI 1.62-3.76; p < 0.001] and long-term [HR 2.12; 95% CI 1.44-3.11; p < 0.001] outcome by multivariate Cox-regression analysis. Elevated plasma levels of GLP-1 are an independent predictor for impaired prognosis in patients with myocardial infarction complicated by CS. The functional relevance of GLP-1 in this context is currently unknown and needs further investigations. www. gov Identifier: NCT00491036.

Outcomes of total hip arthroplasty using dual mobility cups following failed internal fixation of proximal femoral fractures at a mean follow-up of 6years.

Performing total hip arthroplasty (THA) after failed internal fixation of proximal femoral fractures (PFF) is known to be associated with high rates of complications. Dual mobility cups (DMC) are known to lower dislocation events in high-risk patients. Very few reports investigated the outcomes of THA using DMC following failure of internal fixation for PFF. This is a retrospective monocentric continuous study of 31 patients who underwent THA with DMC after failed internal fixation of PFF. The clinical assessment was based on the modified Harris hip score (mHHS) at the last follow-up. The complication rates and radiological analyses were recorded. The mean follow-up period was 5.96±4.2years. At the last follow-up, the mean mHHS was 92.9±9.1 with 71% of the patients describing their operated hip as a forgotten hip. No dislocation or aseptic loosening events were noted. One patient developed a septic loosening of the implant. No significant radiological changes were recorded. Sixteen stems (51.6%) were placed in a neutral position, 13 (42%) in valgus (2.74±1.72°), and 2 (6.4%) in varus (6.94±2.02°). This study emphasizes the advantage of using DMC following failed internal fixation of PFF in reducing dislocation and complication events in this high-risk population.

Cardiologists' knowledge and perceptions of the seasonal influenza immunisation

BackgroundSeasonal influenza immunisation reduces cardiovascular events in high-risk patients, but 50% do not receive routine immunisation. The perceptions and current role of cardiologists in recommending and prescribing influenza immunisation has not been well described. MethodsWe used an exploratory sequential mixed methods design. Semi-structured interviews of 10 cardiologists were performed to identify themes for quantitative evaluation. 63 cardiologists undertook quantitative evaluation in an online survey. The interviews and surveys addressed (a) attitudes and behaviours regarding influenza immunisation and (b) preventative care in cardiology. ResultsOne quarter (25.4%, n = 16) of cardiologists recommended influenza immunisation to all patients. Less than half (49.2%, n = 31) recommended influenza immunisation to secondary prevention patients. Almost 1/3 of respondents (31.7%, n = 20) were uncertain or unaware of the guidelines regarding influenza immunisation and patients with cardiac disease. Most cardiologists believed that general practitioners were responsible for ensuring patients received influenza immunisation (76.2%, n = 48). ConclusionsDespite reducing cardiovascular events in high-risk patients, influenza immunisation is not widely recommended by cardiologists. Further clinician education is needed to address the knowledge gaps which prevent recommendation and uptake of this guideline directed treatment.

Guideline adherence to statin therapy and association with major adverse cardiac events in high-risk patients following major noncardiac surgery

Abstract Introduction Statins are widely used for the prevention of coronary artery disease (CAD) and associated secondary cardiovascular complications. Despite established evidence in acute and chronic cardiovascular disease, the optimal perioperative use of statins remains uncertain. We aimed to evaluate adherence to current guideline recommendations regarding statin therapy in high-risk patients undergoing major noncardiac surgery and its association with major adverse cardiac event (MACE). Methods Class I indications for statin therapy according to current ESC clinical practice guidelines were assessed among consecutive high-risk patients undergoing major noncardiac surgery enrolled in a prospective multicentre cohort study. The primary endpoint MACE, a composite of cardiovascular death and spontaneous acute myocardial infarction, was recorded during 120-day follow up and centrally adjudicated by cardiologists blinded to statin therapy. As a co-primary endpoint, perioperative myocardial infarction/injury (PMI) due to a type 1 MI (T1MI) or likely type 2 MI (lT2MI) within the first three postoperative days was used. After multivariable adjustment with inverse probability of treatment weighting (IPTW) to account for differences between statin and non-statin users, we performed a Cox proportional hazard model with MACE and a logistic regression model with PMI due to T1MI or lT2MI as endpoints. Results Between October 2014 and February 2018, we included 8116 high-risk patients undergoing major noncardiac surgery. 4227 of 8116 patients (52.1%) had at least one class I indication for statin therapy. The most common indication for statin use was CAD in 2235 patients (52.9%) followed by diabetes with comorbidities in 1676 patients (39.6%) and peripheral artery disease in 1514 patients (35.8%). From all patients with a class I indication for statin use, only 2440 (57.7%) were on statins preoperatively. Usage was highest in patients with prior myocardial infarction (828/1110 [74.6%]) and lowest in patients with chronic kidney disease stage 3-5 (494/996 [49.6%]). During the follow up of 120 days, 192 MACE occurred (4.6%) including 116 cardiovascular deaths. After multivariable adjustment, preoperative use of statins was associated with a reduced risk of MACE (weighted hazard ratio 0.59, 95% confidence interval [CI] 0.41-0.86; p = 0.006). PMI due to T1MI or lT2MI occurred in 508 of 4170 (12.2%) patients. After IPTW, the weighted odds ratio for PMI in patients receiving preoperative statin therapy was 1.15 (95%CI 1.01-1.31; p = 0.036). Conclusion Current adherence to guideline-recommended statin therapy in the noncardiac surgery population is suboptimal. The use of statins was associated with reduced rates of adverse cardiac events within 120 days, but not with cardiac PMI.Percentage of patients receiving statinsMACE within 120 days

Abstract 16909: Eicosapentaenoic Acid and Docosahexaenoic Acid Have Competing Effects on Membrane Lipid Dynamics Due to Differences in Structure

Background: Omega-3 fatty acids (n3-FAs) incorporate into vascular cell membranes where they modulate protein function and signal transduction. The n3-FA eicosapentaenoic acid (EPA) delivered in ethyl ester form (icosapent ethyl) reduced a broad range of cardiovascular events in high-risk patients (REDUCE-IT). This was not observed with mixed n3-FA formulations containing docosahexaenoic acid (DHA) in STRENGTH and other trials. These discordant outcomes indicate DHA may counter certain EPA effects due to its additional carbons and double bond. We compared these n3-FA effects on membrane lipid dynamics and width, key determinants of protein function. Methods: Membrane lipid fluidity was measured by fluorescence anisotropy approaches in large unilamellar vesicles (LUVs) of 100 nm diameter containing 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC) and 50 mol% cholesterol with EPA and/or DHA (0-10 mol%). LUVs were treated with the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), at 1 mol% and evaluated using a spectrofluorometer with a polarization accessory. Membrane width ( i.e ., unit cell periodicity) of the samples was determined by small angle x-ray scattering (SAXS). Results: DHA alone increased bulk lipid fluidity as indicated by a dose-dependent reduction in apparent rotational correlation time (ARCT); at 10 mol%, there was a ~20% (p&lt;0.05) reduction from ~19 to ~16 nsec compared to control (untreated membranes). By contrast, EPA had no significant disordering effect except when combined at equimolar levels; the EPA/DHA combination showed a reduction in ARCT to ~18 nsec at 10 mol% that was different from EPA alone (p&lt;0.05). Consistent with these findings, SAXS analysis showed DHA containing membranes had a reduced width compared to EPA by 5% or 3 Å (p&lt;0.05) due to increased trans-gauche isomerizations in the phospholipid acyl chains. Conclusion: EPA maintained membrane fluidity while DHA increased fluidity and thereby reduced membrane width due to its additional carbons and double bond. The EPA/DHA combination increased membrane fluidity compared to control and EPA alone. The disordering effects of DHA may counter EPA stabilizing effects and explain discordant clinical outcomes with different n3-FA formulations.

Abstract 15993: The Association of Aspirin With and Without Statin on Cardiovascular Outcomes in Primary Prevention Patients With Diabetes Mellitus

Background: The role of aspirin in primary prevention of ASCVD amongst high-risk individuals with diabetes mellitus remains unclear. We investigated aspirin use with and without statin and its association with future ASCVD events in a cohort of real-world primary prevention patients with diabetes mellitus. Methods: Primary prevention patients with diabetes were stratified based on HbA1c levels (6.5-7%, 7-9%, &gt;9%) and 10-year ASCVD risk (High-risk [≥20%]). Aspirin use was defined as no use, seldom used (&lt;30% of the time), sometimes used (≥30% - &lt; 70% of the time), and often used (≥70% of the time). Cox regression assessed HRs of myocardial infarction (MI), stroke, and mortality with aspirin use. Results: Of 79, 597 patients with diabetes, 44.6% were classified as high-risk. These patients showed highest utilization of aspirin (45.7%) and statin (44.9%). Compared to high-risk patients with diabetes and an HbA1c of &gt;9% on both a statin and an aspirin, those on statin alone had higher risk of MI [HR MI 1.74 (1.44-2.212), p &lt;0.001], ischemic stroke [HR STROKE 2.52 (1.92-3.29), p &lt;0.001], and mortality [HR 1.67 (1.27-2.19), p &lt;0.001] (Table). Aspirin use alone was associated with higher risk of MI [HR 3.11 (2.42-4.00), p &lt;0.001], ischemic stroke [HR 3.12 (2.08-4.67), p &lt;0.001], and mortality [HR 3.77 (2.71-5.23), p &lt; 0.0004] in the high-risk population with HbA1c &gt;9% (Table). At all A1c levels, patients on no statin or aspirin were at significantly higher risk for MI, stroke, and mortality (Table). In high-risk patients with an HbA1c &gt;9%, ASA use ≥ 70% resulted in significantly lower risk of MI [HR 0.58 (0.49-0.69), p&lt;0.001)], ischemic stroke [HR 0.36 (0.28-0.46), p&lt;0.001] and mortality [HR 0.52 (0.42-0.66), p&lt;0.001]. Conclusion: Low dose aspirin may play a role in prevention of ASCVD events in high-risk patients with diabetes. Future studies can clarify the risk-benefit ratio of using aspirin with statin in patients with poor glycemic control for primary prevention of ASCVD events.

Bridging the gap in cardiovascular care in diabetic patients: are cardioprotective antihyperglycemic agents underutilized?

ABSTRACT Introduction Atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) are two major complications of type 2 diabetes (T2DM). Cardiovascular protection is a key objective, yet not fully reached in clinical practice. Areas covered Both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven their efficacy in reducing major cardiovascular events in high-risk patients with T2DM and SGLT2is in reducing hospitalization for HF in placebo-controlled randomized trials. However, real-life studies worldwide revealed that only a minority of patients with T2DM receive either a GLP-1RA or an SGLT2i and surprisingly even less patients with established ASCVD or HF are treated with these cardioprotective antihyperglycemic agents. Expert opinion Bridging the gap between evidence-based cardiovascular protection with GLP-1RAs and SGLT2is and their underuse in daily clinical practice in patients with T2DM at high risk is crucial from a public health viewpoint. However, the task appears hazardous and the goal not attained considering the current failure. Education of specialists/primary care physicians and patients is critical. Multifaceted and coordinated interventions involving all actors (physicians, patients and broadly health-care system) must be implemented to stimulate the adoption of these cardioprotective antihyperglycemic medications as part of routine cardiovascular care among patients with T2DM.

Postoperative stellate ganglion block to reduce myocardial injury after laparoscopic radical resection for colorectal cancer: protocol for a randomised trial

IntroductionStellate ganglion block (SGB) is usually used in the department of algiatry. But preoperative SGB may reduce adverse cardiovascular events in high-risk patients, although evidence remains sparse. Therefore, we aim...

Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes.

Elevated lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are both associated with adverse events in high-risk patients with established coronary artery disease (CAD). Currently, the association between Lp(a) levels and recurrent cardiovascular (CV) events (CVEs) remained undetermined in patients with different glucose status. Therefore, this study aimed to investigate the prognostic significance of Lp(a) levels for recurrent CVEs in high-risk CAD patients who suffered from first CVEs according to different glycemic metabolism. We recruited 5257 consecutive patients with prior CVEs and followed up for recurrent CVEs, including CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. Patients were assigned to low, medium, and high groups according to Lp(a) levels and further stratified by glucose status. During a median 37-month follow-up, 225 (4.28%) recurrent CVEs occurred. High Lp(a) was independently associated with recurrent CVEs [adjusted Hazard Ratio (HR), 1.57; 95% confidence interval (CI) 1.12-2.19; P = 0.008]. When participants were classified according to Lp(a) levels and glycemic status, high Lp(a) levels were associated with an increased risk of recurrent CVEs in pre-DM (adjusted HR, 2.96; 95% CI 1.24-7.05; P = 0.014). Meanwhile, medium and high Lp(a) levels were both associated with an increased risk for recurrent CVEs in DM (adjusted HR, 3.09; 95% CI 1.30-7.34; P = 0.010 and adjusted HR, 3.13, 95% CI 1.30-7.53; P = 0.011, respectively). This study demonstrated that elevated Lp(a) levels were associated with an increased recurrent CVE risk in patients with CAD, particularly among those with pre-DM and DM, indicating that Lp(a) may provide incremental value in risk stratification in this population.

PCSK9 inhibition in atherosclerotic cardiovascular disease.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a novel class of hypolipidemic drugs, providing an additional therapeutic option over conventional hypolipidemic treatments. Given the constantly lowering recommended LDL-C goals, low goal achievement rate and low compliance with treatment, new hypolipidemic drug classes may substantially contribute to residual risk reduction for atherosclerotic cardiovascular disease (ASCVD). This review aims to summarize contemporary evidence on the clinical role of PCSK9i in ASCVD prevention. PubMed and MEDLINE databases were searched for keywords in studies on PCSK9i and ASCVD. Approved PCSK9i are the monoclonal antibodies (Mabs), evolocumab and alirocumab, targeting PCSK9, and inclisiran, a small interfering RNA inhibiting PSCK9 synthesis. Overall, PCSK9i effectively reduced LDL-C and other atherogenic lipoproteins, including apolipoprotein B and lipoprotein(a) primarily. PSCK9i Mabs improved imaging markers reflecting coronary atherosclerotic plaque vulnerability and reduced ASCVD events in high-risk patients after short-term treatment ( < 3 years follow-up). They are currently indicated as a third-line treatment for secondary prevention and primary prevention in patients with familial hypercholesterolemia at high risk of not achieving their LDL-C goals. Patients with higher baseline ASCVD risk receive greater benefits from PCSK9i. Recent evidence suggests that evolocumab was effective and safe after long-term treatment. Ongoing trials investigate new therapeutic indications for PCSK9i while their cost-effectiveness is still being considered. PCSK9i is a novel hypolipidemic drug class currently indicated for reducing residual risk in secondary ASCVD prevention and high-risk patients.

Impact of bempedoic acid on cardiovascular events in high risk patients with statin intolerance: The clear outcomes study

Impact of bempedoic acid on cardiovascular events in high risk patients with statin intolerance: The clear outcomes study

Long-term lipid apheresis reduces cardiovascular events in high-risk patients with isolated lipoprotein(A) elevation

Long-term lipid apheresis reduces cardiovascular events in high-risk patients with isolated lipoprotein(A) elevation

Relationship between Serum Proprotein Convertase Subtilisin/Kexin Type 9 Concentration and Prevalence of Coronary Artery Calcium in a Community-Based Sample of Japanese Men.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for reducing low-density lipoprotein cholesterol (LDL-C) and cardiovascular events in high-risk patients. However, the influence of circulating PCSK9 concentration on atherosclerotic plaque formation in the general population remains unknown. We assessed the relationship between serum PCSK9 concentration and coronary artery calcium (CAC) prevalence in the general population. Community-dwelling Japanese men (n=622) aged 46-82 years without a history of cardiovascular disease and lipid-lowering medications were included. Serum PCSK9 concentration and CAC score were measured using the Agatston method, and the multivariable analysis was used to assess their association. CAC was defined as an Agatston score of ＞10. We conducted further analysis stratified by age (＜60, 60-69, and ≥ 70 years). The average age, LDL-C, and median serum PCSK9 concentration were 68 years, 122 mg/dL, and 240 ng/mL, respectively. After multivariable adjustment for traditional cardiovascular risk factors, no significant association was observed between serum PCSK9 concentration and CAC prevalence (adjusted relative risk [aRR] 1.05, 95% confidence interval [CI] 0.97-1.13). With age stratification, serum PCSK9 concentration was significantly associated with CAC prevalence in men aged ＜60 years (aRR 1.38, 95% CI 1.01-1.88) but not in men aged 60-69 years (aRR 0.96, 95% CI 0.85-1.10) or ≥ 70 years (aRR 1.08, 95% CI 0.99-1.19). A higher serum PCSK9 concentration was associated with a higher CAC prevalence in men aged ＜60 years, which was independent of traditional cardiovascular risk factors.