bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of 10-year risk for recurrent atherosclerotic cardiovascular events in a secondary prevention population: Insights from CHART-2 and Suita studies in the Japanese population
Authors: Oyama K , Kokubo Y , Nochioka K , Hamaya R , Shiroto T , Takahashi J , Miyamoto Y , Shimokawa H , Yasuda S
Published: October 2024

Background

Despite the European Society of Cardiology (ESC) guidelines advocating risk prediction models for secondary prevention in established atherosclerotic cardiovascular disease (ASCVD) patients, such models for Japanese individuals remain limited, owing to their comparatively lower ASCVD risk than Western populations. Given this gap, there is a need to develop tailored risk assessment tools for Japanese ASCVD patients to optimize secondary prevention strategies.

Purpose

Leveraging data from two large-scale, long-term cardiovascular cohorts in Japan, our aim was to develop and externally validate a 10-year risk model predicting recurrent cardiovascular events among patients with established ASCVD.

Methods

The CHART-2 and Suita studies, large-scale prospective observational multicenter cohort studies in Japan, served as the primary data sources for this investigation. From the CHART-2 study, which comprised 3,560 patients with a history of coronary artery disease or ischemic stroke, we derived our risk model. External validation was conducted using data from the Suita study, which included 445 patients with similar ASCVD backgrounds. The primary outcome of interest was a composite endpoint encompassing cardiovascular death, myocardial infarction, or stroke. Variable selection was performed based on clinically relevant factors previously employed in established risk scores (SMART, REACH, and TRS 2°P risk scores). Logistic regression was utilized for model development, and the predictive performance was assessed using the C-index.

Results

Over a median follow-up of 10.1 years, the derivation cohort experienced 756 cardiovascular events. Patients in the derivation cohort had an average age of 68.9 ± 10.6 years, with 91% and 24% having a history of coronary artery disease and ischemic stroke, respectively. Using logistic regression, the multivariate model revealed a higher recurrent risk associated with several factors including age, smoking status, systolic blood pressure, diabetes, renal function, number of ASCVD events, atrial fibrillation, lipid levels, left ventricular systolic dysfunction, and statin use. A simple risk score based on these predictors demonstrated a >5-fold gradient of 10-year recurrent risk with a C-index of 0.65 (95% CI 0.63-0.68, Figure). The prediction model was externally validated in the Suita study wit 245 cardiovascular events and a median follow-up of 10.4 years, showing good discriminative ability with a C-index of 0.64 (95% CI 0.60–0.68).

Conclusion

Our newly developed prediction model offers a valuable tool for identifying individuals at heightened risk of recurrent cardiovascular events over a 10-year period, thereby facilitating more targeted and effective secondary prevention strategies tailored to the unique characteristics of Japanese ASCVD patients.
Impact of measured or calculated small dense LDL cholesterol compared with apolipoprotein B or non-HDL cholesterol for long-term secondary prevention in patients with stable coronary artery disease
Authors: Koba S , Satoh N , Ito Y , Yokota Y , Tsunoda F , Sakai K , Nakamura Y , Shoji M , Hirano T , Shinke T
Published: October 2024

Background

This study was aimed to investigate whether directly measured small dense low-density lipoprotein cholesterol (D-sdLDL-C) can predict long-term coronary artery disease (CAD) events compared with LDL-C, non–high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), and estimated sdLDL-C (E-sdLDL-C) determined by Sampson’s equation in patients with stable CAD.

Methods

D-sdLDL-C measured at Showa University, and E-sdLDL-C were evaluated in 790 male and 244 female patients with stable CAD. CAD events defined as sudden cardiac death, onset of acute coronary syndrome, and/or need for coronary revascularization were monitored for 12 years. Cut-points of D-sdLDL-C, E-sdLDL-C, LDL-C, non-HDL-C, and apoB were determined by receiver operating characteristic curves.

Results

CAD events were observed in 238 male and 67 female patients. The Kaplan–Meier event-free survival curves showed that patients with D-sdLDL-C ≥32.1 mg/dL had an increased risk for CAD events (chi-square from log-rank test = 7.23), whereas risk in patients with E-sdLDL-C ≥36.2 mg/dL was not. In the group with high D-sdLDL-C, the multivariable-adjusted hazard ratio (HR) was 1.47, 95% confidence interval (CI) 1.15-1.89, and it remained significant after adjustment for LDL-C, non-HDL-C, or apoB. These results remained significant in the patients treated with statin. HRs for high LDL-C, non-HDL-C, or apoB were not statistically significant after adjustment for high D-sdLDL-C. The high D-sdLDL-C enhanced risk of high LDL-C, non-HDL-C, and apoB (HR 1.73, 95%CI 1.27-2.37). Conclusions: High D-sdLDL-C can predict long-term recurrence of CAD in stable CAD patients independently of apoB and non-HDL-C by distinguishing the patients at high risk. D-sdLDL-C is an independent risk-enhancer for secondary CAD prevention whereas E-sdLDL-C is not.Figure
Association of serum testosterone levels with left atrial size, function, and risk of atrial fibrillation in adult men: observational and mendelian randomization analyses
Authors: Cho S H , Yang P S , Jang E S , Kim D H , Yu H T , Kim T H , Uhm J S , Pak H N , Lee M H , Joung B Y
Published: October 2024

Background

Numerous studies have investigated the association between serum testosterone levels, testosterone replacement therapy (TRT), and cardiovascular risk. However, research examining the relationship between testosterone levels and atrial fibrillation (AF) risk remains limited. We comprehensively analyzed the association between total testosterone (TT) levels, intermediary phenotypes such as left atrium (LA) size and function, and the risk of AF in middle-aged and older men.

Methods

We utilized data from the UK Biobank, a population-based prospective cohort, focusing on 179,988 White men who had complete serum TT level data and no AF history. Observational associations between TT levels and LA imaging traits, as well as AF risk, were estimated using multivariable regression and time-dependent Cox regression models, treating TT levels as a time-varying variable. Genetic associations were examined by Mendelian randomization (MR), using both UK Biobank and external large consortia genome-wide association study data.

Results

During the median follow-up of 11.8 years (IQR 10.9–12.5), we observed 13,847 incident AF cases (7.7%). Participants with normal TT levels (≥ 300 ng/dL) showed a 15% reduced risk of AF (HR of 0.85 [95% CI, 0.82–0.89]) compared to those with low TT (< 300 ng/dL). Interestingly, participants undergoing TRT experienced a 51% higher risk of AF (1.51 [1.09–2.07]). Furthermore, each 1-standard deviation increase in TT levels was associated with a reduced AF risk (OR of 0.91 [0.89–0.93]) and an improved LA emptying fraction (1.29 [1.06–1.58]). Applying age-specific cutoff values for low TT levels highlighted a more pronounced AF risk reduction in participants with normal TT. MR analyses supported these observations, suggesting potential causal relationships between TT levels and both LA function and AF risk.

Conclusions

Our findings suggest that low TT levels are associated with reduced LA function and increased risk of AF, both observationally and genetically, indicating that serum TT could serve as a surrogate marker or even a potential causal mediator in the development of AF.Abstract tableAbstract figure
Composition of non-HDL cholesterol and residual cardiovascular risk in secondary prevention
Authors: Hansen M K , Olesen K K W , Thrane P G , Gyldenkerne C , Stoedkilde-Joergensen N , Andersen M H , Maeng M , Mortensen M B
Published: October 2024

Background

Non-high-density lipoprotein cholesterol (non-HDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD) and is a recommended secondary prevention treatment target. However, the composition of non-HDL-C, that is, the relative contribution of remnant cholesterol (remnant-C) and low-density-lipoprotein cholesterol (LDL-C), is not considered for cardiovascular risk prediction.

Purpose

To examine ASCVD risk by composition of non-HDL-C.

Methods

Based on the Western Denmark Heart Registry, we established a cohort of patients with ischemic heart disease, including patients with acute coronary syndrome or stable angina pectoris, undergoing coronary angiography for evaluation of coronary artery disease between 2011 and 2020. A complete lipid panel within 1 year after coronary angiography on statin treatment was required. Patients with triglycerides >4.5 mmol/L were excluded. Exposures were remnant-C, LDL-C, non-HDL-C, and composition of non-HDL-C. The latter was defined as remnant-C of non-HDL-C, and LDL-C of non-HDL-C, in percentages. Cox regression analyses obtained adjusted hazard ratios (aHR) for myocardial infarction, ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death), and all-cause death occurring from 1 year after coronary angiography to end of follow-up November 1, 2022.

Results

The secondary prevention cohort included 42,341 statin-treated patients (67.7% were men; median [IQR] age 66 [58-73] years). During median 4.1 years of follow-up, 3,846 patients developed ASCVD. Per 1 mmol/L increase in remnant-C, LDL-C, and non-HDL-C, the aHR for ASCVD was 1.41 (95% CI 1.28-1.55), 1.12 (95% CI 1.08-1.17), and 1.17 (95% CI 1.13-1.21), respectively (Figure 1). The relative contribution of remnant-C and LDL-C was median (IQR) 24.6% (18.5-33.1) and 75.4% (66.9-81.5) of non-HDL-C, respectively. When remnant-C constituted a larger percentage of non-HDL-C (and LDL-C a lower percentage), the aHR for ASCVD showed a linear increase in risk whereas the opposite trend was observed for LDL-C (Figure 2). Thus, per 10% increase in remnant-C of non-HDL-C, the aHR of ASCVD was 1.06 (95% CI 1.03-1.09) compared to 0.94 (95% CI 0.91-0.97) per 10% increase in LDL-C of non-HDL-C. Results were comparable for myocardial infarction and all-cause death, and by age, sex, and other clinically relevant subgroups.

Conclusions

The composition of non-HDL-C is strongly associated with ASCVD risk, with the risk escalating as remnant-C constitutes a larger percentage, and LDL-C a smaller percentage, of non-HDL-C. These findings challenge current guidelines and demonstrate the value of considering composition of non-HDL-C in clinical practice for more accurate risk assessment.Figure 1Figure 2
Subgroup analysis of diabetes in COVID-positive revascularized patients: implications for clinical management
Authors: Musayev O , Dashdemirov R , Ibrahimov F , Musayev K , Dadashova G , Gardashova E , Alimli Z , Gasimzade S , Mushtagzadeh N , Aliyeva F
Published: October 2024

Background

The management of revascularized patients with COVID-19, particularly in the presence of diabetes mellitus (DM), presents significant challenges. Understanding the clinical outcomes in this subgroup is essential for optimizing patient care during the pandemic.

Purpose

This study aimed to investigate the clinical outcomes of revascularized COVID-positive patients with and without DM, focusing on revascularization methods, hospitalization rates, mechanical ventilation requirement, mortality, stroke incidence, and presentation of acute coronary syndrome (ACS) subtypes.

Methods

A retrospective analysis was conducted on the cohort of 620 COVID-positive revascularized patients. Among them, 267 patients had diabetes mellitus (DM), while 353 patients did not. Data on revascularization methods, hospitalization rates, mechanical ventilation requirement, mortality, stroke incidence, and ACS presentation were collected and compared between the two groups. Statistical analysis was performed to assess the significance of differences observed.

Results

Among the 620 COVID-positive revascularized patients, 267 (43.1%) had diabetes mellitus, while 353 (56.9%) did not. Demographic analysis revealed that 299 (84.7%) of the COVID-positive patients with diabetes mellitus were male, compared to 181 (67.8%) of those without diabetes mellitus. This difference in gender distribution between the two groups was statistically significant (p < 0.001). Additionally, smoking was more prevalent among COVID-positive patients without diabetes mellitus (38.8%) compared to those with diabetes mellitus (22.5%), with a significant difference observed (p < 0.001) (Table 1). Among the revascularized patients, a higher proportion of patients with diabetes mellitus underwent coronary artery bypass grafting (CABG) compared to those without DM (32.6% vs. 24.1%, p = 0.019). Patients with diabetes exhibited significantly higher hospitalization rates (27.0% vs. 15.6%, p = 0.001) and a trend towards increased mechanical ventilation requirement (11.1% vs. 3.6%, p = 0.121). However, mortality rates, stroke incidence, and ACS presentation did not significantly differ between the two groups (Table2).

Conclusion

This study underscores the heightened vulnerability of revascularized COVID-positive patients with DM, as evidenced by higher hospitalization rates and a trend towards increased mechanical ventilation requirement. These findings emphasize the importance of tailored management strategies for this high-risk subgroup to optimize patient outcomes during the ongoing COVID-19 pandemic.Table 1Table 2
Is the obesity paradox leading to a less stringent secondary prevention strategy in post-acute coronary syndrome patients?
Authors: Moreira M , Frias D , Schmidt C , Alves Dias V , Magalhaes S , Santos M , Torres S
Published: October 2024

Introduction

Patients with acute coronary syndrome (ACS) are at very high risk of recurrent cardiovascular (CV) events. Despite being a major CV risk factor, obesity was associated with best survival in patients with ACS, the so-called "obesity paradox". It is uncertain if this finding is leading to a less stringent secondary prevention strategy in this group of patients, and whether it influences prognosis.

Purpose

To analyze the impact of obesity on outcomes after ACS and on other CV risk factor management.

Methods

Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 cardiac rehabilitation (CR) program in 2017, with a follow-up of 24 months. Patients were classified in 2 groups according to body mass index (BMI) at baseline: Group 1 (G1) were obese patients (BMI≥30 kg/m2), and Group 2 (G2) were non-obese patients (BMI<30kg/m2). Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization.

Results

198 patients were included (mean age of 60.3±10.7 years, 82% male) with a mean BMI of 27.7±4.2 kg/m2. Forty-seven patients (23.7%) had a BMI≥30 kg/m2. Patients in G1 were more likely to have hypertension (79% vs 55%; p=0.003) and diabetes (36% vs 20%; p=0.022). CR program was associated with smoking cessation, significant BMI (G1: -0.69 (95%CI: -0.40 to -0.10); G2: -0.39 (95%CI: -0.20 to -0.57) and LDL-Cholesterol (LDL-C) reduction (G1: -38 (95%CI: -25 to -50); G2: -29 (95%CI: -22 to -36), and functional capacity improvement (G1: +1.2 METs (95%CI: +0.9 to +1.5); G2: +1.1 METs (95%CI: +1.0 to +1.4) in both groups at 3 months, with similar magnitude of improvement. At 24 months, BMI had returned to baseline values in both groups, while the improvement in smoking status, LDL-C and functional capacity persisted. At 24 months, MACE occurrence was numerically increased in obese group (G1: 26.1% vs. G2: 17.2%, p=0.182), with a statistically significant higher incidence of non-fatal recurrent ACS in G1 (17% vs. 7.3%, p=0.048).

Conclusions

ACS patients with obesity have worse prognosis, despite the similar improvement in CV risk profile. Our data also suggests that, despite the short-term improvement in BMI, current treatment strategies are not effective at achieving a persistent weight control over 24-months.
Improvement of myocardial lipolysis in iodine-123-beta-methyl-P-iodophenyl-pentadecanoic acid scintigraphy in patients with idiopathic triglyceride deposit cardiomyovasculopathy treated with Tricaprin
Authors: Ono R , Miyauchi H , Iimori T , Hirano K , Kobayashi Y
Published: October 2024

Background

Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare intractable cardiovascular disorder (Orphanet ORPHAcode: 565612) in which defective intracellular lipolysis results in heart failure and coronary artery disease. Myocardial scintigraphy with iodine-123-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) is useful for evaluating myocardial TG metabolism and its washout rate (WR) reflects myocardial lipolysis. A decreased WR (<10%) of BMIPP is one of the diagnostic criteria for TGCV. CNT-01, the active ingredient of which is tricaprin, a medium-chain triglyceride, has the potential to facilitate myocardial lipolysis in a mouse model. However, the effects of CNT-01 (tricaprin) on BMIPP scintigraphy in patients with TGCV remain unclear.

Purpose

To evaluate the effects of CNT-01 on BMIPP-WR in patients with TGCV.

Methods

An investigator-initiated, randomized, double-blind exploratory trial (Phase IIa) was conducted. Ten patients with idiopathic TGCV in our hospital were enrolled and orally administered 1.5 g/day of CNT-01 or placebo for 8 weeks. The endpoint was the delta WR on BMIPP scintigraphy. All the participants underwent BMIPP scintigraphy after overnight fasting. Following the protocol recommended by the Japanese Society of Nuclear Cardiology, 111 MBq of BMIPP was intravenously injected at rest after fasting for ≥ 12 h. Early and delayed images were obtained after 20 and 180–210 min, respectively. BMIPP scintigraphy at baseline and 8-week was performed using the same SPECT apparatus. WR is defined as the ratio of the difference between the counts in the early image and time-decay-corrected delayed image divided by the former. We used a recently proposed algorithm for calculating the WR based on the total count and analyzed the WRs (Ann Nucl Cardiol. 2023;9(1):19-25).

Results

A total of 5 patients were assigned to placebo and 5 patients were assigned to CNT-01. During the protocol, delta BMIPP-WRs were -6.18 ± 4.43 and 5.44 ± 2.57 % (95% confidence intervals, -12.33 to -0.03 and 1.88 to 9.00) in the placebo and CNT-01 groups, respectively. The baseline-adjusted difference in delta BMIPP-WR between the two groups was significant (p=0.005) (Picture). No significant changes were observed in clinical parameters.

Conclusion

This study demonstrated that CNT-01 improved myocardial lipolysis in patients with TGCV as measured by BMIPP scintigraphy.
Efficacy of combination therapy with statin and ezetimibe versus high dose statin monotherapy in secondary prevention in high-risk patients
Authors: Halatiu V B , Benedek I , Rodean I P , Benedek T
Published: October 2024

Background

Secondary prevention in patients with acute coronary syndrome focuses on lowering low-density lipoprotein (LDL) cholesterol below 55 mg/dL. In all statin-naïve patients at high risk (LDL-cholesterol target <55 mg/dL), initiation of high-intensity statin monotherapy is recommended by ESC guidelines. Nonetheless, at one month, a significant proportion of patients do not reach their LDL-cholesterol target.

Purpose

The aim of this study was to compare lipid-lowering therapy with statin monotherapy versus statin with ezetimibe in secondary prevention in patients at high risk.

Methods

The current prospective study included 264 consecutive patients admitted with acute ST elevation myocardial infarction who underwent percutaneous coronary intervention. None of the patients had taken lipid-lowering drugs in the previous 12 months. Patients were randomly assigned to one of two treatment groups: Group 1 - rosuvastatin 40 mg (n= 144) and Group 2 - rosuvastatin 40 mg and ezetimibe 10 mg (n= 120). All patients' lipid profiles were assessed upon admission and after one month of lipid-lowering treatment.

Results

At baseline, no patient had LDL cholesterol level lower than 55 mg/dL. There was no significant difference in lipid profile at baseline between the two groups (all p > 0.05). No differences were observed between the two groups in terms of baseline LDL-cholesterol deviation from the target (103.4% versus 99.70%; p= 0.66). As expected, the combination therapy reduced LDL-cholesterol at one month significantly higher compared to high-dose statin monotherapy (-59.65% versus -37.54%; p< 0.0001). After one month of treatment, only 47.92% of patients in Group 1 reached the LDL-cholesterol target (<55 mg/dL) compared to 90.00% of the patients in Group 2 (p<0.0001; R.R.= 0.53).

Conclusion(s)

Our findings show that statin and ezetimibe combination therapy is more effective in reduction in LDL-cholesterol levels and reaching targets compared to statin monotherapy alone. In statin-naïve patients at high risk, early initiation of the statin and ezetimibe combination instead of statin monotherapy should be taken into account in secondary prevention, for an earlier reach of the LDL-cholesterol target and to reduce the overall cardiovascular risk.
Estimate and prognosis of patients who are candidates for treatment with eicosapentaenoic acid after an acute coronary syndrome
Authors: Cordero A , Fernandez Olmo R , Fernandez-Friera L , Manzano S , Bonanad C , Cortez G , Oterino A , Castellano J M , Alvarez-Alvarez B , Flores Blanco P J , Gonzalez-Juanatey J R
Published: October 2024

Background

Treatment with eicosapentaenoic acid (EA) has been shown to reduce the incidence of cardiovascular adverse events (MACE) in patients at high cardiovascular risk with mildly to moderately elevated triglyceride values (>135 mg/dl) and non-elevated (<100 mg/dl) low-density lipoprotein cholesterol (LDLc).

Methods

We performed a multicenter and retrospective study using the ongoing registries of acute coronary syndrome (ACS) patients of 7 hospitals from Spain. Patients with LDLc <100 mg/dl and triglycerides >135 mg/dl were analyzed as candidates to EA.

Results

We included 14,483 patients discharged after an ACS, mean age 67.5 (13.3), 28.1% women and 30.4% with an ST-elevation ACS. Mean LDLc was 99.8 (38.5) mg/dl and median triglycerides 120.5 (interquartile range 90-197) mg/dl. A total of 3,028 (20.9%) were classified as candidates for EA, and they had the same mean age (p=0.87) but significantly higher prevalence of diabetes (35.1% vs. 21.9%), dyslipidemia (63.5% vs. 50.1%), previous coronary heart disease (CHD) (25.9% vs. 13.9%), or heart failure (HF) (3.6% vs. 2.5%). Candidates less frequently had an ST-elevation ACS (26.6% vs. 34.1%; p=0.02) and the incidence of Killip >1 was equivalent in candidates vs. non-candidates (16.6% vs. 17.7%; p=0.15).

Median follow-up was 1223 (interquartile range 570-2040) days. All-cause mortality was 15.0% (n= 2,166), and 34.71% (n=5,019) of the patients experienced a first MACE. Candidates for EA had higher mortality (18.4% vs. 14.0%; HR: 1.22 95% CI 1.11-1.35) and MACE (39.0% vs. 33.6%; HR 1.14 95% CI 1.06-1.21) rates. Multivariate analysis (figure), adjusted for age, sex, diabetes (DM), previous coronary heart disease (CHD) or heart failure (HF), and medical treatments at discharge, identified an independently higher risk for all-cause mortality among candidates for EA (HR: 1.15 95% CI 1.04-1.26) [Figure 1] and for MACE (HR: 1.14 95% CI 1.05-1.20). The risk was consistent in all subgroups except for the case of mortality, but not for MACE, and previous ACS (figure 2) were a significant interaction (p=0.01) was observed

Conclusions

Approximately 20% of patients discharged after an ACS could be candidates for EA, and this subset of patients are at higher risk of death or a first MACE.
Effects of lipid-lowering therapies on lipoprotein(a) levels in patients with dyslipidemia: a systematic review and network meta-analysis of 64 randomised controlled trials
Authors: Loh E D W , Koh M Y , Toh K Z X , Teo Y N , Teo Y H , Syn N L X , Tan B Y Q , Yeo L L L , Loh W J , Lim A Y L , Poh K K , Kong W K F , Yeo T C , Chai P , Sia C H
Published: October 2024

Background

Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease. However, there has yet to be a drug approved specifically for lowering Lp(a). There is paucity of studies evaluating the use of current lipid-lowering agents, and their effects, if any, on Lp(a).

Purpose

We aimed to identify and compare the effects of lipid-lowering therapies on Lp(a) levels, cardiovascular and safety outcomes, in patients with dyslipidemia.

Methods

A systematic search was performed across four databases (PubMed, Embase, Scopus, Cochrane) for randomised controlled trials (RCTs) published from inception to 3 January 2023. The percentage change of serum Lp(a) levels, cardiovascular and safety outcomes were compared among statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin), fibrates, ezetimibe, niacin, PCSK9 inhibitors (alirocumab, evolocumab, bococizumab) and inclisiran, in patients with primary dyslipidemia. Frequentist network meta-analysis was performed to compare the treatment effects among different drug classes, stratified by use of background statin therapy.

Results

A total of 64 RCTs were included, comprising 55,256 patients. In patients on background statin therapy, PCSK9 inhibitors significantly lowered Lp(a) levels, compared with placebo (mean difference [MD] -26.8, 95% confidence intervals [95%CI] -30.8 to -22.7), ezetimibe (MD -21.6, 95%CI -31.4 to -11.8), fibrates (MD -19.4, 95%CI -37.4 to -1.5), and niacin (MD -13.8, 95%CI -25.6 to -2.1). PCSK9 inhibitors were associated with lower risk of major adverse cardiovascular events and similar risk of treatment-related adverse events than placebo. Comparing the PCSK9 inhibitors, evolocumab achieved greater Lp(a)-lowering than alirocumab in patients on background statin therapy (MD -11.4, 95%CI -18.6 to -4.1), including those with heterozygous familial hypercholesterolemia. Niacin also achieved 12.9% (95%CI 1.8 to 24.0) reduction in Lp(a) compared with placebo, but had a higher risk of treatment-related adverse effects than fibrates. Statin monotherapy did not affect Lp(a) levels, regardless of type or intensity of statin therapy. Ezetimibe and fibrate had no effect on Lp(a) levels.

Conclusions

PCSK9 inhibitors produced the greatest effect on Lp(a) levels, compared with other lipid-lowering therapies. Further studies into PCSK9 inhibitors are necessary to characterise their efficacy and safety specifically for Lp(a)-lowering, and elucidate the impact of Lp(a) reduction on cardiovascular risk.% change in Lp(a) levels
Comorbidity neural network model for personalised recommendations in cardiometabolic risk factor management: towards early precision medicine in routine clinical practice
Authors: Dibner Y , Brandt N , Curcin V , Krentz A , Lozhkina A , Luster A , Pere A , Jaun A
Published: October 2024

Background and Aims

Hypertension and hypercholesterolaemia often develop in tandem to confer a risk of cardiovascular disease that may be more than additive. The present study explored early comorbid therapeutic intervention, i.e., beyond individual disease silos, while minimising data bias to provide clinical decision support tools that are portable across clinics.

Methods

A neural network was created to reproduce UK national clinical guidelines with an accuracy higher than 95%. Relying on real-world evidence from the UK primary care Clinical Practice Research Datalink electronic health record resource, a transfer learning methodology was then applied to achieve recommended risk factor goal attainment after two years. Shapley values derived from game theory were used to define similar digital twin cohorts, and to evaluate individualised recommendations that deviated from national clinical guidelines by rejecting a no-benefit hypothesis retrospectively in a classical proportion test. The methodology was ported to an independent hold-out dataset with anonymized records from six primary care clinics in the South of England.

Results

The adult patient population (n=469,496, mean+SD age 61+11yr; M 56% vs F 44%; primary 84% vs secondary prevention 16%) included 101,255 diagnosed for hypertension and 112,180 for cholesterol management. While a majority of the 52,504 therapeutic decisions in a test set agree with single morbidity guidelines, for 4639 deviations from the guidance, a significant minority was identified for whom alternative therapy was recommended. Rejecting a no-clinical benefit hypothesis at the 95% confidence level in a retrospective analysis, 1367 decisions showed statistically significant better outcomes over guidelines, for example by escalating anti-hypertensive therapies for patients receiving statin therapy (1085) or by complementing anti-hypertensive therapy with a statin (158). Similar findings were obtained when tested in a hold-out dataset with 13,725 decisions for 6531 patients.

Conclusions

The results support the contention that machine learning can identify patient subgroups for whom comorbid intervention deviating from clinical guidelines may be appropriate. A novel aspect of the study is the demonstration of clinically portable and actionable application of machine learning in the context of comorbid cardiometabolic diseases. The results represent practical steps towards personalised precision medicine for cardiovascular comorbidity in routine clinical practice.
High discontinuation rate of statins among PCSK9i users: a nationwide study from 2015-2023
Authors: Engebretsen I , Oedegaard K , Halvorsen S , Bugge C , Kristiansen I , Stoevring H , Munkhaugen J
Published: October 2024

Background

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are recommended as additional lipid-lowering drug treatment for high-risk patients if the low-density lipoprotein cholesterol (LDL-C) targets are not achieved with statins and ezetimibe alone. Nationwide data from clinical practice on the use of PCSK9i are lacking. In 2015, PCSK9i became available in Norway with reimbursement restricted to patients with familial hypercholesterolemia (FH) and/or atherosclerotic cardiovascular disease (ASCVD) with LDL-C above certain levels.

Purpose

To investigate the use and adherence of lipid lowering drugs among a nationwide cohort of PCSK9i users, utlizing complete pharmacy dispensation data.

Methods

Information on all PCSK9i users ≤80 years with at least one year of follow-up after the first dispensation were extracted from the Norwegian Prescribed Drug Registry. We evaluated adherence to PCSK9i by calculating the proportion of days covered (PDC) during the initial year of PCSK9i therapy. Poor adherence was defined as PDC <80%, and discontinuation was defined as a gap in treatment ≥180 days during the follow-up period. We analyzed treatment patterns of statins and ezetimibe during the 1-year period before and after PCSK9i initiation by determining the proportion of patients with at least one dispensation of statin and/or ezetimibe treatment.

Results

A total of 2,997 PCSK9i users were identified. Median age at treatment initiation was 62 (IQR: 13) years and 43% were female. Non-adherence to PCSK9i was observed in 16% of the patients, and 18% discontinued treatment (Table). Non-adherence to PCSK9i was more prevalent in females, and in the lowest and highest age quartiles. No significant difference in non-adherence was found among patients with ASCVD compared to patients with FH. In the year preceding PCSK9i initiation, 74% of patients used statins (including combinations with ezetimibe), 11% used ezetimibe monotherapy, and 15% did not use any statin or ezetimibe treatment (Figure). During the year following PCSK9i initiation, 35% used statins (including combinations), 17% used ezetimibe monotherapy, and 48% did not use any statin or ezetimibe treatment. Among patients with ASCVD, 72% used statins prior to PCSK9i initiation, and 22% used statins after. Among patients with FH, 77% used statins prior to PCSK9i initiation, while 51% used statins after.

Conclusion

In this nationwide study of incident PCSK9i users, we observed a substantial decrease in usage of statins and ezetimibe following PCSK9i initiation. Further, almost 1 in 5 patients discontinued treatment with PCSK9i. There is a large potential for optimizing treatment and adherence to PCSK9i and conventional lipid-lowering drugs among Norwegian patients with ASCVD and familial hypercholesterolemia.Adherence and discontinuation to PCSK9iUse of statin and ezetimibe
Lipid goal attainment across baseline socioeconomic and clinical factors comparing an "inclisiran first" implementation strategy and usual care: subgroup analysis of VICTORION-INITIATE
Authors: Koren M , Rodriguez F , Toth P P , Ali Y , Kleeman K , Sarwat S , Abbas C , East C
Published: October 2024

Background

Addressing inequities in cardiovascular care has become a public health priority. Recent results from VICTORION-INITIATE, a pragmatically designed, randomised clinical trial showed the benefit of using inclisiran immediately if patients with atherosclerotic cardiovascular disease (ASCVD) fail to achieve low-density lipoprotein cholesterol (LDL-C) <70 mg/dL (1.8 mmol/L) on maximally tolerated statins.

Purpose

To evaluate effectiveness and safety of an "inclisiran first" implementation strategy (IF) versus usual care (UC) in subgroups that may be associated with healthcare inequities.

Methods

VICTORION-INITIATE was conducted at 45 representative clinical settings across 20 states in the USA. Patients with ASCVD randomised 1:1 (stratified by insurance status) received open-label inclisiran 284 mg at Days 0, 90 and 270) plus UC or UC alone (lipid management directed by treating physicians). Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per lipid guidelines. We compared efficacy and safety endpoints for IF and UC in prespecified subgroups (race, ethnicity, sex, renal function and statin intensity) and by income level (post-hoc analysis).

Results

The study randomised 450 patients. Baseline demographic and clinical parameters were balanced between study arms (≥65 years of age: IF: 63.1%, UC: 61.3%; non-White: IF: 15.6%, UC: 15.1%; Hispanic: IF: 13.8%, UC: 16.9%; female: IF: 29.8%, UC: 32.0%; income ≤$50,000: IF: 58.7%, UC: 58.2%; estimated glomerular filtration rate ≥30 to <60 mL/min/1.73m2: IF: 20.0%, UC: 17.8%; no statins at baseline: IF: 9.8%; UC: 10.2%). Across all subgroups, more patients achieved LDL-C goals at Day 330 with IF vs UC (Figure 1). Within the UC arm, the proportions of patients achieving LDL-C <70 mg/dL and <55 mg/dL, respectively, were numerically lower for non-White (8.8% and 2.9%) and Hispanic (10.5% and 2.6%) than White (24.6% and 10.2%) and non-Hispanic (24.9% and 10.3%) patients. We did not observe differences in LDL-C goal attainment for these subgroups in patients receiving IF. Compared with UC, IF resulted in greater mean percentage change in other lipids and lipoproteins from baseline to Day 330, irrespective of subgroup (Figure 2). Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs compared similarly between IF and UC for each subgroup (IF: 35.5−69.2%, UC: 34.2−84.2%, and IF: 3.2−16.9%, UC: 0.0−36.8%, respectively).

Conclusions

VICTORION-INITIATE enrolled a diverse population reflective of "real-world" US clinical practice. The IF strategy consistently resulted in higher rates of LDL-C goal attainment for all subgroups studied and did not lead to differences in lipid outcomes by race or ethnicity as compared to usual care. No additional safety concerns for the IF strategy were identified.
Trajectories of weight and their impact on cardiac remodeling and function 16 years after bariatric surgery
Authors: Piche M , Tremblay X , Blais M , Premont C , Mathieu M A , Auclair A , Pettigrew M , Marin-Couture E , Lajeunesse-Trempe F , Marceau S , Poirier P
Published: October 2024

Introduction

Obesity is a major risk factor for heart failure, particularly heart failure with preserved left ventricular (LV) ejection fraction. Surgical treatment of obesity have significant beneficial short-term effects on weight loss and on cardiac function; its long-term impact on cardiac remodeling and function remains largely unknown.

Purpose

We examine the long-term effect of bariatric surgery on cardiac remodeling and function in adults with preserved LV ejection fraction.

Methods

Forty-four individuals with severe obesity [body mass index (BMI) ≥35kg/m2] and preserved LV ejection fraction (≥50%) who underwent bariatric surgery (biliopancreatic diversion with duodenal switch [BPD-DS]) were included. Anthropometric measurements and echocardiography were obtained at baseline, 12 months and 16 years follow-up.

Results

Mean age of participants (71% female) was 44 ± 8 years and body mass index (BMI) 49.6 ± 6.1 kg/m2. Bariatric surgery led to marked weight reduction and significant improvements in obesity-related metabolic conditions/comorbidities (hypertension, dyslipidemia, type 2 diabetes). Mean percentage of weight loss at 12 months was 37.1 ± 7.0 %. Percentage of weight regain at 16 years averaged 8.9 ± 35.0 %. Bariatric surgery was associated with a significant reduction in indexed LV mass and LV hypertrophy (p <0.01), and improvement in LV diastolic function parameters (p <0.01) at 12 months. In many participants, cardiac remodeling parameters deteriorated at 16 years follow-up compared to the echocardiographic measurements taken at 12 months post-surgery. Prevalence of LV diastolic dysfunction increased at 16 years (81 vs. 38%; p<0.001), even after adjusting for age. Weight regain at 16 years (regaining >10% of weight lost; n=25; 57%) was not found to be associated with a worsening in cardiac remodeling compared to those who maintained weight loss, except for indexed LV mass (-9.3 ± 10.6 vs. -5.5 ± 7.8 g/m2.7; p=0.04) and LV end-diastolic diameter (-5.4 ± 4.0 vs. -3.5 ± 3.3 cm; p=0.01).

Conclusion

Bariatric surgery (BPD-DS) leads to durable long-term weight loss. Weight regain following bariatric surgery does not appear to have adverse effect on cardiac remodeling and function. Surgical treatment of obesity may be an effective and safe way to prevent clinical cardiac dysfunction and heart failure related to obesity.
Left atrial volume in obesity and hypertension: an innovative "ideal human" index allows for weighing their impact - a non-contrast cardiac CT study
Authors: Sosnowski M , Harpula J , Dobrolinska M , Parma Z , Mlynarski R , Wojakowski W
Published: October 2024

Left atrial (LA) enlargement is a common and early feature of cardiac involvement in the natural history of obesity and arterial hypertension (AH). Mechanisms involved in this process are cumulative, and partly shared, thus separating and balancing their contributions is challenging. In a proportion of patients referred for coronary artery calcium (CAC) scoring, these clinical entities are present. The LA volume (LAV) is relatively easy to quantify from a CT scan. Measured LAV values can be misleading unless constitutional parameters (height (h) or body size area (BSA), are considered. We introduced a new indexing parameter, consisting of height and the difference between numerical values of height and BSA. In the "ideal human", the difference is zero. Any deviation from this value determines the share of body mass regardless of height.

Aim

We hypothesize that a novel indexation approach allows for earlier detection of the increased LAV in normotensive and AH patients considering the body mass index.

Method

We retrospectively analyzed CT data from 2535 patients, 1658 w (64±10 ys), and 876 m (aged 6±11ys), with CAC scoring over the last 15 years The LAV was determined by using commercially available software. The raw and indexed (for h, BSA, and the novel parameter [h+ (h-BSA)]) LAV volumes were compared in patients with normal BMI (<25kg/msg), overweight (25-29.9), and obesity (≥30) who with normal blood pressure or with AH.

Results

The LAV was larger in high BMI categories than in normal BMI. In non-AH subjects, the LAV increased from an average of 71 ml (normal) to 80 ml (overweight) and 90 ml (obese). In AH, the LAV increase showed a similar trend of averages (77, 88, 94 ml, F=2.59,p<0.01). Indexing LAVs were non-concordant, as shown in Figure. Thus, one can recognize that LAV normalization for the new index has brought the differences most evident and persuasive. In normal BMI, indexation ways did not significantly affect the LAV estimation. Whilst the body weight increased, no difference could be recognized for values indexing for BSA (red). The LAV indexation for height (blue) cannot help diagnose its increase in obesity. The distinguishing strength can be seen while using the [h-(h-BSA)] denominator (green). It indicates that in any scenario, body mass gain plays a greater role in the LAV increase than AH does.

Conclusions

Body mass is a more important factor that is associated with LAV than AH.. Common methods of LAV indexing, especially referred to as BSA, introduce errors leading to values mimicking normality in non-healthy people and should be forbidden. The proposed indexation way can help overcome the observed discrepancies and support early recognition of the consequences of obesity and hypertension.
Obesity paradox, weight-free anthropometric measures, and major adverse cardiovascular events in the elderly: Insight from the Northern Shanghai Study
Authors: Xu C , Zhao S , Zhang Y
Published: October 2024

Aims

Many studies have investigated the obesity paradox in the elderly. However, besides body mass index (BMI), many other anthropometric measures, such as the waist-to-hip ratio (WHR), provide a better indication of body fat distribution and may be more useful in a geriatric population.

Methods

3285 participants aged over 65 years old from the Northern Shanghai Study were included in this analysis. Eight anthropometric measures, including weight-related measures (BMI, weight-adjusted-waist index, body shape index and body surface area) and weight-free measures (WHR, waist-to-height ratio, body roundness index, relative fat mass) were measured and calculated with standard methods. Major adverse cardiovascular events (MACEs) included the non-fatal myocardial infarction, non-fatal stroke or cardiovascular death.

Results

Participants had an average age of 71.4 years and 1428 (43.47%) were men. The median follow-up was 5.4 years (IQR, 4.4-7.3 years) and 218 events occurred. Participants with obesity (BMI ≥ 28 kg/m2) were associated with a higher risk of MACEs compared with the normal (adjusted Hazard ratio = 1.54, 95% confidence interval (CI): 1.07-2.22, P=0.020). Restricted cubic splines also highlighted the robust correlation between high BMI and high MACEs risk (Pfor overall=0.025, Pfor nonlinear=0.339). Similarly, the aHR for the incidence of MACEs in WHR quartile 4 versus quartile 1 was 1.96 (95% CI: 1.26-3.05, P=0.003). When WHR was examined as a continuous variable, the result remained unaltered (Pfor overall=0.020, Pfor nonlinear=0.353). In adjusted model, all four weight-free measures were significantly associated with increased risk of MACEs (all P<0.05), while only two weight-related measures were related to the risk of MACEs.

Conclusion

In the elderly, BMI and alternative anthropometric measures showed no evidence of an "obesity paradox". Weight-free measures were more relevant to a risk of MACEs.Take home message
Long-term changes in cardiac geometry and mechanics after bariatric surgery- insights from the FatWest study
Authors: Grymyr L M D , Gerdts E , Nadirpour S , Nedreboe B G , Cramariuc D
Published: October 2024

Background

Patients with severe obesity have a high prevalence of subclinical cardiac organ damage including impaired longitudinal and radial cardiac mechanics. Previous studies on the impact of bariatric surgery on cardiac remodeling, most of them with short patient follow-up, have yielded inconsistent results.

Purpose

To assess progressive changes in cardiac geometry and mechanics up to five years following bariatric surgery.

Methods

In the prospective Bariatric Surgery on the West Coast of Norway (FatWest) study, cardiac remodeling was assessed by 2D echocardiography preoperatively and at six months, one year and five years after Roux-en-Y gastric bypass in a cohort of 97 patients (44±10 years, 72% women, body mass index [BMI] 41.8±4.8 kg/m²). Excess weight loss (EWL) was calculated as: absolute weight loss/(initial weight-ideal weight)x100. Left ventricular (LV) size was assessed by the LV mass/ height^2.7, LV longitudinal mechanics by the peak global longitudinal strain (GLS) and radial mechanics by the midwall shortening (MWS). LV myocardial oxygen demand was estimated from the LV mass-wall stress-heart rate product. Right ventricular diameter was measured in the basal one-third of the ventricular cavity. Left atrial (LA) reservoir function was assessed by the LA emptying fraction.

Results

After a mean follow-up of 63±13 months, the average postoperative EWL was 66%. Overall, both right ventricular diameter, LV mass index, LV GLS, myocardial oxygen demand and LAEF (68% vs. 64%) improved significantly at the 5-year follow-up (all p<0.05), while MWS remained unchanged (Figure). Prevalence of normal LV geometry increased gradually from 56% to 80%, while that of LV hypertrophy fell from 36% to 16% (p<0.001). Analyses of temporal trends showed that improvement in BMI, LV mass and LV GLS occurred during the first postoperative year (Figure).

In Cox regression analysis, a low 5-year GLS was associated with preoperative hypertension after adjustment for age, sex, preoperative diabetes mellitus, and postoperative changes in BMI, mean blood pressure and myocardial oxygen demand (p<0.01). In a similar linear model, after adjustment for the same covariates, LV mass index at the 5-year follow-up was independently related to the magnitude of the postoperative BMI reduction (R² = 0.58, p<0.001).

Conclusion

Ventricular size and longitudinal mechanics are significantly improved 5 years after bariatric surgery, with the reverse remodeling occurring during the first postoperative year. Residual abnormal 5-year LV geometry and mechanics are related to preoperative hypertension and suboptimal BMI reduction.Figure