bluuebunny/crossref_metadata_2025 huggingface dataset:
The ApoB/LDL-C ratio predicts cardiovascular events in coronary artery disease patients independent of type 2 diabetes status
Authors: Larcher B , Plattner T , Mader A , Vonbank A , Leiherer A , Muendlein A , Drexel H , Saely C H
Published: October 2024

A high ApoB/LDL-C ratio reflects small LDL particle size which like type 2 diabetes (T2DM) is associated with insulin resistance. Whether the ApoB/LDL-C ratio and the presence of T2DM are mutually independent predictors of cardiovascular events is unclear and is addressed in the present study.

We enrolled a large high-risk cohort of 1200 patients with coronary artery disease. T2DM was diagnosed according to current ADA guidelines. Prospectively, cardiovascular events were recorded over a mean follow-up period of 10.5±4.9 years.

At baseline, the ApoB/LDL-C ratio was significantly higher in patients with T2DM (n=422) than in subjects who did not have T2DM (0.81±0.18 vs. 0.74±0.15 p<0.001). During follow-up, 662 patients suffered cardiovascular events. The Apo B/LDL-C ratio predicted cardiovascular events in univariate analysis (HR=1.11 [1.03-1.20] p= 0.006), and the event rate was higher in patients with than in those without T2DM (62.2% vs. 52.3%; p=0.001). In a multivariate adjusted Cox regression model both the ApoB/LDL-C ratio and T2DM significantly predicted cardiovascular events in a mutually independent manner, with standardized adjusted HRs of 1.11 [1.03-1.20]; p=0.008 and 1.39 [1.18- 1.64]; p<0.001, respectively.

We conclude that in subjects with coronary artery disease the ApoB/LDL-C and T2DM are mutually independent predictors of cardiovascular events.
Perfusion metabolism mismatch predicts short-term complications in Takotsubo syndrome
Authors: Sato T , Otaki Y , Suzuki Y , Kurihara M , Nanasato M , Iguchi N , Isobe M
Published: October 2024

Background

Takotsubo syndrome (TTS) is a transient cardiac condition triggered by sudden emotional or physical stress characterized by LV dysfunction in the absence of obstructive epicardial coronary artery disease. 123I-BMIPP, an iodinated fatty acid analogue, can identify impaired myocardial metabolic activity. With the use of dual SPECT protocol, reduced uptake of 123I-BMIPP compared to perfusion which is called perfusion-metabolic mismatch is observed in apical regions in TTS. The mismatch may indicate jeopardized but viable myocardium, reflecting transient ischemic damage or metabolically stunned myocardium. However, the association between the perfusion metabolism mismatch in TTS and its complications remains underexplored.

Purpose

Our study aimed to analyze the degree of perfusion metabolism mismatch at the acute phase in TTS and investigate its association with short-term complications.

Methods

This retrospective study conducted between 2012 and 2024 at a single center included 82 patients diagnosed with TTS. Patients underwent dual SPECT imaging using 99mTc or 201 Tl and 123I-BMIPP within two weeks of admission. We applied quantitative analysis using QGS/QPS software from Cedars-Sinai. Total perfusion deficit ("TPD") was calculated based on sex-matched normal limits providing the extent of perfusion abnormality. Meanwhile, perfusion-metabolism mismatch scores ("worsen") were determined by comparing the total BMIPP counts to the total counts of perfusion. We then assessed the correlation of these imaging findings with biomarkers, regional wall motion abnormalities, and the occurrence of short-term complications. Short-term complications included heart failure, left ventricular outflow (LVOT) obstruction, mitral regurgitation, cardiac arrhythmia, cardiogenic shock, left ventricle (LV) rupture, and cardiac death during the hospitalization period.

Results

All study patients exhibited wall motion abnormalities seen in apical segments. The count of myocardial segments with regional wall motion abnormality was correlated with both TPD (r=0.34, p=0.002) and perfusion metabolic mismatch score (r=0.40, p<0.001). TPD had a moderate correlation coefficient with max CK-MB (r=0.44, p<0.001) and troponin T (r=0.40, p<0.001) levels. However, perfusion metabolic mismatch did not display correlations with max CK-MB (r=0.05, p=0.65), and Troponin T (r=0.12, p=0.28) levels. Among 82 patients, 37 patients experienced any short-term complications. Importantly, patients with short-term complications had elevated perfusion mismatch scores compared to those without short-term complications (14.0 [6.0-22.5] vs. 5.0 [3.0-10.0], p<0.001). However, no significant difference was observed in TPD between the two groups (9.0 [4.5-20.0] vs. 7.0 [3.0-12.0], p=0.130).

Conclusions

Our research highlights a significant association between perfusion-metabolism mismatch and an increased risk for short-term complications in patients with Takotsubo syndrome.
Causal associations of insulin and Lp(a) levels: a Mendelian randomization study
Authors: Lejawa M , Golawski M , Fronczek M , Osadnik T , Pawlas N , Lisik M , Paneni F , Ruscica M , Jozwiak J , Gierlotka M , Banach M
Published: October 2024

Background

Numerous observational studies have demonstrated circulating lipoprotein(a) [Lp(a)] to be inversely related to occurrence of type 2 diabetes [T2D]. However, this is not consistently supported by Mendelian randomization [MR] studies. In vitro studies have shown insulin to downregulate Lp(a) expression, which might be another mechanism behind the correlation observed between Lp(a) and T2D.

Purpose

In this MR study, we investigated the influence of genetically predicted levels of insulin on genetically predicted Lp(a) levels to elucidate the potential causal links between Lp(a) and diabetes.

Methods

Independent genetic variants associated with insulin levels were acquired from a meta-analysis of genome-wide association studies (GWAS, N=151,013). Summary data for Lp(a) were acquired from a GWAS study in the UK Biobank (N=361,194). Inverse-variance-weighted (IVM) method was used to perform a two sample MR study. Sensitivity analysis was conducted via MR Egger, weighted median (WME), as well as leave-one-out analysis.

Results

Genetically predicted insulin levels were negatively associated with Lp(a) levels according to IVM estimate (p=0.003). In sensitivity analysis, WME supported this result (p=0.0002), while MR-Egger was not statistically significant (p=0.11). Leave-one-out analysis did not show the results to depend on any single variant.

Conclusion

This MR study provides robust evidence supporting the association between plasma insulin levels and decreased Lp(a) concentration. These findings suggest that hyperinsulinemia triggered by insulin resistance can be in part responsible for the observed negative correlation between low Lp(a) and T2D risk.

Figure 1. Genetic associations between insulin levels and Lp(a). Each genetic variant included in the analysis is represented as a point + 95% CI. Localization on the horizontal axis represents the correlation of the variant with exposure (plasma fasting insulin, inverse variance normal transformed values). Localization on the vertical axis represents the correlation of the variant with outcome (Lp(a), natural log transformed values). Lines represent estimates of different MR methods.Figure 1.
PCSK9 inhibitors in HIV patients with dyslipidemia
Authors: Datla S , Ali B , Sattouf Z
Published: October 2024

Introduction

Cardiovascular disease has become increasingly prevalent in the HIV (human immunodeficiency virus) population. Antiretroviral therapy and HIV itself independently increase the risk of dyslipidemia. While statins are currently the predominant therapy to treat dyslipidemia in HIV patients, drug-drug interactions and adverse drug events can limit their use. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a naturally occurring inhibitor of the LDL-receptor pathway. PCSK9 inhibitors offer an alternative in patients who cannot tolerate or need additional therapy in addition to statin for optimal dyslipidemia management.

Purpose

The purpose of this study is to compare major adverse cardiovascular events in HIV patients on a PCSK9 inhibitor (evolucumab, alirocumab, inclisiran) vs patients not on a PCSK9 inhibitor.

Methods

A retrospective cohort study was conducted using electronic medical records from a global federated health research network. The TriNetX network was searched on February 10, 2024, including records from 2020 to 2024. Patients were included based on a diagnosis of HIV status and concomitant dyslipidemia. Patients with HIV and dyslipidemia on a PCSK9 inhibitor were propensity-score matched for age, sex, race, and comorbidities with patients who were not on a PCSK9 inhibitor. The outcomes were mortality, myocardial infarction, heart failure and stroke.

Results

A total of 485 patients were included in the study. PCSK9 inhibitor use associated with 9% lower odds of all-cause mortality (odds radio, .29; 95% CI, 0.18-0.48; p<.0001). PCSK9 inhibitor use was also associated with 8% lower odds of heart failure (odds radio, .63; 95% CI, 0.47-0.85; p<.0023). No significant associations were noted for myocardial infarction (odds radio, .87; 95% CI, 0.63-1.21; p=0.406) or stroke (odds radio, .67; 95% CI, 0.45-1.01; p=0.052).

Conclusion

The role of dyslipidemia in HIV is challenging due the complex pathophysiology of HIV. There is an apparent increased risk of cardiovascular disease from the infection itself as well current antiretroviral therapies. While current guidelines recommend the use of statins as first line therapy for dyslipidemia in this population, the drug-drug interaction of statins with ARTs, as well as their side effects, limit their use at times. PCSK9 inhibitors are associated with lower odds of all-cause mortality and heart failure. No significant association was seen for myocardial infarction or stroke. They should be considered as an early intervention alongside statins in HIV patients with dyslipidemia. Further research should be done for the long term safety and tolerance of this therapy as well as cost-effectiveness and access to PCSK9 inhibitors in this population.
Lipoprotein (a) and lipidemic parameters in PCSK-9 inhibitor patients. Experience from a specialized centre in Greece
Authors: Dima I , Skoumas I , Andrikou I , Grigoriou K , Tsioufis K , Vlachopoulos C
Published: October 2024

Background

Previous studies have reported an association between Proprotein Convertase Subtilsin-kexin type 9 (PCSK-9) inhibition and levels of lipoprotein a [Lp (a)], having a possible effect on the cardiovascular benefit achieved by their use. The purpose of this study was to investigate the effect of PCSK-9 inhibitor use in Lp (a) and other lipidemic parameter levels in the population of a specialized Lipids Clinic during a follow up period of 24 months.

Methods

We enrolled 143 (80 males, mean age 60 years old) patients who were on PSCK-9 inhibitor treatment from the outpatient lipid clinic of our hospital. Information were obtained regarding the presence of coronary artery disease (CAD) and CAD risk factors. CAD was present in 72 patients (63%), Familial Hypercholesterolaemia (FH) in 97 patients (85%) and 20 (18%) patients suffered from statin intolerance. Patients were on triple lipid lowering therapy (statin plus ezetimibe plus PCSK-9 inhibitors) except for those with statin intolerance who were either on dual therapy (ezetimibe plus PCSK-9 inhibitors, N=8) or single PCSK-9 inhibitors therapy (N=10). Lp (a) levels and lipid parameters such as Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglycerides (TG) were measured at baseline, 3 months, 12 months and 24 months of treatment. Additionally, patients were categorized according to baseline Lp (a) levels in two groups, Group 1 (<70mg/dl) (N=62), Group 2 (≥70 mg/dl) (N=26). A comparison of the response in lipid parameters between these two groups was performed.

Results

Mean value for Lp (a) in the whole population was 54mg/dl, 48mg/dl, 44mg/dl, and 45mg/dl at baseline, 3, 12 and 24 months, respectively. T test analysis revealed a significant reduction in Lp (a) levels after 12 months (P<0.05) There was also a significant reduction in LDL levels at all time points (165mg/dl to 78mg/dl, 85mg/dl, 78mg/dl respectively, P<0.05), a reduction in triglyceride levels at 3 and 12 months (125mg/dl to 110mg/dl, 108mg/dl respectively, P<0.05) and an increase in HDL levels after 12 months (50mg/dl to 53mg/dl, P<0.05). Moreover, in Group 1, the response in LDL levels was higher after 12 months of treatment with PCSK-9 inhibitors (158mg/dl to 69mg/dl, P<0.05) compared to Group 2 (155mg/dl to 86mg/dl), indicating that high levels of Lp (a) seem to define the response to treatment.

Colclusions

Besides the detrimental effect in LDL levels, PCSK-9 inhibition has an impact on HDL and TG levels. Lp (a) was also reduced indicating an additional important effect of this inhibition. While higher levels of Lp (a) seem to correlate with poorer response to treatment, our findings enhance the already known importance of Lp (a) as a prognostic factor.
Efficacy and severity of side-effects of rosuvastatin compared to other statins post-heart-transplantation
Authors: Van Dijk B C J , Bos D , Roest S , Goedendorp-Sluimer M M , Brugts J J , Constantinescu A A , Van Der Boon R M A , Taverne Y J H J , De Boer R A , Budde R P J , Caliskan K , Manintveld O M
Published: October 2024

Introduction

The International Society of Heart and Lung Transplantation (ISHLT) 2022 guideline recommends statin therapy in heart transplantation (HTx) patients, with the therapeutic low-density lipoprotein (LDL) target being <2.5 mmol/L. Particularly pravastatin is recommended, given proven beneficial effects on long-term clinical outcome and the low prevalence of side effects. Yet, in the general population, rosuvastatin has been shown to be even more potent.

Purpose

We investigated the lipid-lowering effect and severity of side-effects of rosuvastatin compared to less potent statins in HTx patients.

Methods

In this before-after study, we included all HTx patients whom were prescribed a change from the statin they were using to rosuvastatin, for better cardiovascular risk management and/or because of side-effects, between February 2018 and February 2023. We evaluated the weight, lipid profile and side-effects (including myalgia, cramps, stiffness and weakness) of these patients up to one year prior to and after the statin change. At the same time, side-effects were measured in a visual analogue scale (VAS) ranging from 0-10, with the average score of side-effects utilized for analysis. We compared the differences using a Wilcoxon signed rank test.

Results

Out of 299 HTx patients, we included 114 patients, with a median age of 58 [IQR 50-67] years at switch of whom 31 (27%) were females. Median time since HTx was 9 [IQR 5-15] years. The distribution and dosage of prescribed statins before and after switch can be found in Table 1. Compared to statins used prior to therapy change, rosuvastatin was associated with lower total cholesterol, LDL- and triglyceride levels, with high density lipoprotein (HDL) levels remaining the same (Table 2). No difference in bodyweight was found (Table 2). Before switch, 41 (36%) patients achieved the target of LDL-levels below 2.5 mmol/L. After switch, 86 (75%) patients achieved the target of LDL levels below 2.5 mmol/L. Rosuvastatin shows a trend towards a lower prevalence of side-effects (Table 2).

Conclusion

In HTx patients that were prescribed a change of statin due to better cardiovascular risk management and/or complaints of side-effects, rosuvastatin is related to a more favorable lipid profile, without additional side-effects, compared to other statins. Furthermore, many more patients achieve the guideline recommended LDL-target. Ongoing research should determine whether this translates to a better clinical outcome.
Low-density lipoprotein cholesterol goal attainment with "inclisiran first" versus usual care in patients with atherosclerotic cardiovascular disease
Authors: Rodriguez F , Koren M , East C , Ali Y , Kleeman K , Sarwat S , Abbas C , Toth P P
Published: October 2024

Background

Rapid and sustained attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals is critical for patients with atherosclerotic cardiovascular disease (ASCVD). In VICTORION-INITIATE, inclisiran administered twice-yearly by a healthcare professional earlier in the treatment pathway allowed more patients with ASCVD to achieve and sustain LDL-C goals vs current usual care (UC).

Purpose

To evaluate cumulative LDL-C exposure in the overall population and LDL-C goal attainment and safety in subgroups of participants (type of ASCVD, timing of ASCVD event, and history of statin intolerance) who received an "inclisiran first" implementation strategy (IF; adding inclisiran immediately on failure to achieve LDL-C <70 mg/dL [1.8 mmol/L] with maximally tolerated statins) compared with UC.

Methods

VICTORION-INITIATE was a 330-day, prospective, pragmatically designed trial that randomised participants 1:1 (stratified by insurance status) to IF (open-label inclisiran 284 mg at Days 0, 90 and 270 plus UC) or UC alone (lipid management directed by treating physician’s discretion). The study took place at 45 sites across 20 states in the USA. Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per clinical practice guidelines. This prespecified subgroup analysis evaluated LDL-C goal attainment by timing of the most recent ASCVD event (<1 year/≥1 year prior to consent), ASCVD subtype (coronary heart disease [CHD], peripheral arterial disease [PAD], and cerebrovascular disease [CVD]) and statin intolerance status. Cumulative LDL-C exposure over time in the overall population and safety by subgroup were also evaluated.

Results

Of 450 patients randomised to IF or UC, 11.1% and 84.2% had an ASCVD event <1 year or ≥1 year prior to consent, respectively; 91.8%, 18.2% and 14.7% had a history of CHD, CVD or PAD, and 25.8% were statin intolerant. Cumulative exposure to LDL-C to Day 330 was lower in patients treated with IF vs UC (mean time-adjusted LDL-C: 42.4 mg/dL vs 90.7 mg/dL, Figure). Significantly more patients who received IF achieved LDL-C goals of <70 mg/dL and <55 mg/dL at Day 330 vs UC, irrespective of subgroup (Table). Across subgroups, the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs were similar between IF and UC (IF: 52.6−71.2%, UC: 46.2−66.0% and IF: 10.7−28.3%, UC: 11.4−22.2%, respectively).

Conclusions

Participants with ASCVD and LDL-C >70 mg/dL who received IF had lower cumulative LDL-C exposure over the study period than those treated with UC. IF resulted in rapid and sustained achievement of LDL-C goals regardless of ASCVD subtype, event timing and statin intolerance. The safety profile of IF was consistent across the subgroups analysed.
Safety and Efficacy of Moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease: a meta-analysis
Authors: Alves Kelly F , Oliveira Macena Lobo A , Aquino De Moraes F C , Morbach V , Kendi Tsuchiya Sano V , Menegaz De Almeida A , Marciano Consolim-Colombo F , Laurinavicius A , Goncalves De Sousa M , Batista Souza J
Published: October 2024

Background

Atherosclerotic cardiovascular disease (ASCVD), affects approximately 18.6 million individuals worldwide, poses an important healthcare challenge. Despite the established efficacy of both high-intensity statin monotherapy (HIS) and moderate-intensity statin plus ezetimibe (MIS+EZT) in ASCVD management, the optimal treatment strategy remains unclear.

Purpose

This meta-analysis seeks to assess the impact of moderate-intensity statin plus ezetimibe (MIS+EZT) versus high-intensity statin monotherapy (HIS) on LDL < 70mg/dl; Total Cholesterol; LDL; High Density Cholesterol (HDL) and triglycerides levels. Our goal is to synthesize the existing evidence and pinpoint areas that warrant further investigation.

Methods

A thorough literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane databases, focusing on studies that compared the effects of moderate-intensity statins plus ezetimibe with high-intensity statin monotherapy in ASCVD patients.

Results

In the 13 included studies, involving 8,592 patients, of which 4,525 (52.67%) received moderate-intensity statin plus ezetimibe treatment. The follow-up period ranged from 12 to 219 weeks, with participant ages varying from 66 to 76.5 years in the MIS+EZT group and from 67 to 75.9 years in the HIS group. Analysis revealed significant MIS+EZT-associated with greater percentages in Low Density Lipoprotein (LDL) < 70 (Odds Ratio (OR) 1.76; 95% CI [1.26; 2.45]; p=0.001; I²=73%), LDL reduction (Mean Difference (MD) -5.05 mg/dL; 95% CI [-9.02;-1.07]; p<0.013; I²=56%;); Total Cholesterol reduction (MD -7.91 mg/ dL; 95% CI [-14.90; -0.91]; p<0.027; I²=60%); Triglycerides reduction (MD -8.20 mg/ dL; 95% CI [-13.05; -3.35]; p<0.001; I²=2%;); There was no statistical difference between groups in Drug Adverse reaction (Risk Ratio (RR) 1.19; 95% CI [0.79; 1.78]; p=0.404; I²=0%); and Drug intolerance (RR 0.78 ; 95% CI [0.32; 1.92]; p=0.584; I²=35%).

Conclusions

This meta-analysis underscores the effectiveness of MIS+EZT in enhancing significant clinical outcomes for ASCVD patients, as evidenced by improvements in a greater percentage of patients achieved the LDL <70 target, LDL, Total Cholesterol and Triglycerides levels . Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between the two groups.
The upfront lipid-lowering combination therapy of statins and ezetimibe vs statin monotherapy in the reduction of cardiovascular outcomes. A meta-analysis.
Authors: Banach M , Jaiswal V , Ang S P , Sawhney A , Deb N , Penson P , Toth P
Published: October 2024

Background

Despite some data in last few years, there is still some inconsistency concerning the effectiveness and safety of the upfront intensive lipid lowering combination therapy (LLT; of moderate to high intensity statin therapy and ezetimibe) in comparison to high intensity statin therapy and recommended by some guidelines stepwise therapy approach.

Purpose

We sought to evaluate the efficacy of combination LLT compared with statin monotherapy for cardiovascular outcomes, LDL-C reduction, and associated adverse events.

Methods

A systematic literature search was conducted using PubMed, Embase, and ClinicalTrial.gov to identify relevant articles published from inception until 29th December 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CI).

Results

A total of 11 studies (8 randomized controlled trials and 3 cohort studies) with 106,358 were involved in the analysis. The mean age of the patients in the combination LLT and statin monotherapy group was 65.3 and 65.7 years, respectively. Pooled analysis shows that combination LLT significantly reduces the LDL-C level from the baseline (MD, -12.13 mg/dl [0.31 mmol/l] (95%CI: -18.26 to -5.99 mg/dl), p<0.001), all-cause mortality (ACM) (OR, 0.75, 95%CI: 0.62 to 0.92, p=0.01), cardiovascular mortality (CVM) (OR 0.75, 95%CI: 0.66 to 0.84, p<0.001), major adverse cardiovascular events (MACE) (OR, 0.72 95%CI: 0.63 to 0.82, p<0.001), non-significant reduction in the incidence of stroke (OR 0.82, 95%CI: 0.66 to 1.01, p=0.06) when compared with statin monotherapy alone. Similarly, the therapy discontinuation rate was comparable between combination LLT and statin monotherapy groups (OR, 0.87 (95%CI: 0.53 to 1.40), p=0.56). The risk of adverse events related to the gastrointestinal tract (OR, 1.12 (95%CI: 0.93 to 1.36), p=0.23) and musculoskeletal system (OR, 0.88 (95%CI: 0.52 to 1.50), p=0.65) was comparable between both the groups of patients.

Conclusion

Combination LLT was associated with an overall greater reduction in LDL-C, a lower risk of ACM, MACE, and CVM compared to statin monotherapy alone.Forest Plot of desired outcomes.Central illustration with key findings.
Score-2 in heavy smokers: are we underestimating the risk?
Authors: Cosmi D , Mariottoni B , Tarquini B , Cosmi F
Published: October 2024

Background

The shared diagnostic decision-making process in patients with atypical chest pain is challenging, especially when functional tests are negative. SCORE2 (1) can help in making decisions. In this score, the risk is assessed based on geographical origin, age, sex, current smoking, systolic blood pressure, cholesterol values.

However, it does not take into account the quantity of cigarettes smoked but only the current binary value, yes or no. In our study we wanted to evaluate the impact of smoking on prognosis, considering the number of cigarettes smoked and in particular focusing on heavy smokers.

Methods

In the last 15 years we evaluated 3,588 outpatients aged >35 years (average 64±9, women 55%) for the presence of stable chest pain. We excluded 290 patients who had ECG changes compatible with recent ischemia, history of myocardial infarction or any other major cardiovascular event, evidence of heart failure, left ventricular dysfunction, or cardiomyopathies. In the other 3,298 cases we applied the traditional classification of typical, atypical angina and non-anginal pain. A functional test was performed in all patients. In 2,774 patients with atypical chest pain and negative functional test we evaluated the extent of cardiovascular risk based on SCORE2 and the number of cigarettes currently smoked. One year follow-up was carried out to evaluate vital status and any fatal and non-fatal cardiovascular events.

Results

Table 1 shows the events in patients classified according to the degree of cardiovascular risk of SCORE2 and in heavy smokers (≥ 20 cigarettes per day) aged <70 years as a cathegory in itself. In moderate smokers (<20 cigarettes/day) of any age, the risk was considered binary as in the conventional assessment. Tables 2 and 3 show the risk stratification in male and female patients. SCORE2 is unable to intercept the extremely high risk of heavy smokers aged <70 years.

This happens both in males, considered at moderate risk in 76% of cases but with a rate of fatal events of 2.4% and as many non-fatal events, both in women with a risk considered moderate in 80% of cases but with a 12% rate of fatal events (as seen in Table 1).

Conclusions

SCORE2 does not consider the quantity of cigarettes smoked per day, so if we rely on it heavy smokers seem to have a moderate risk. On the contrary, based on our analysis, they all have an extremely high risk, regardless of other risk factors, and in any case higher than non-smoking or moderately smoking patients. Especially heavy smoking women aged <70 years with atypical chest pain and negative functional tests have an extreme risk of fatal cardiac events (12% at one year). Probably these patients (male and female), regardless of the outcome of functional tests, should be sent for an anatomical evaluation for the detection of high-risk stenosis, as well as firmly urged to improve lifestyles and treat risk factors .
Are metabolically healthy obese individuals really a benign cardiovascular group? An analysis of 162,590 participants with measures of arterial stiffness in UK BIOBANK
Authors: Ananda R , Solomon B , Ray K K
Published: October 2024

Background

There is conflicting evidence as to whether so called metabolically healthy but overweight and obese individuals are at increased cardiovascular risk or mortality.

Purpose

We assessed whether metabolic health correlates with vascular health among these individuals using severity of arterial stiffness as a proxy for vascular health and cardiovascular risk.

Methods

Participants in UK Biobank with body-mass index (BMI) and arterial stiffness index (ASI) recorded at initial assessment between 2006-2010, and free from stroke and myocardial infarction and not underweight (BMI<18.5kg/m2) were included. Participants were stratified by BMI (normal, overweight, obese) and presence of metabolic abnormalities (hypertension, diabetes, dyslipidaemia). The primary outcome was the severity of ASI analysed using multivariate-adjusted linear regression.

Results

Of 162,590 participants, 55.0% were female, mean age was 57 years (SD 8), 42.5% were overweight and 24.4% obese. Within the normal BMI strata, 50.7% had ≥1 metabolic abnormality. Compared to individuals with normal BMI and no metabolic abnormalities (ref group), increased weight or metabolic abnormalities were similarly associated with higher ASI; adjusted β-coefficient [β] 0.35, 95%CI 0.30 to 0.40 for participants with normal BMI and ≥1 metabolic abnormality; β 0.32, 95%CI 0.26 to 0.37 for overweight participants without metabolic abnormalities. Obese individuals with no metabolic abnormalities had higher ASI (β 0.65; 95%CI 0.57 to 0.74) but was lower than overweight participants with metabolic abnormalities (β 0.80; 95%CI 0.75 to 0.84). Obese participants with metabolic abnormalities had the highest ASI (β 1.07; 95%CI 1.02 to 1.12) among all six metabolic combinations, p<0.001 for each vs ref group. Sensitivity analysis suggested higher ASI with increasing number of metabolic abnormalities within BMI categories.

Conclusion

Excess weight and metabolic abnormalities, are independently associated with adverse measures of vascular health to a similar degree, suggesting that the so called metabolically healthy obese are not a benign group. Primary prevention strategies should be considered in overweight, or obese individuals even if metabolic abnormalities are absent.
A new natural product derived from cyclosorus terminans provides cardiometabolic protection against obese-induced cardiac dysfunction in rats via suppressing mitochondrial dysfunctions and apoptosis
Authors: Maneechote C , Pratchayasakul W , Arunsak B , Chattipakorn S C , Chattipakorn N
Published: October 2024

Background

The development of a novel pharmacological target for obesity has long been considered challenging in mitigating the global cardiovascular complications and mortality. Given the cytotoxic effects associated with various anti-obesity drugs, there is growing interest in exploring new natural products as potential sources for bioactive agents to treat obesity-associated diseases with minimal side effects. While Cyclosorus terminans extract has demonstrated anti-diabetic and anti-obese efficacies in adipose-derived stem cells, its cardioprotective effects in high-fat diet (HFD)-induced obese-insulin resistance rat models have never been elucidated.

Purpose

To examine the effects of long-term Cyclosorus terminans treatment on metabolic, cardiac, and mitochondrial functions and apoptosis in HFD-induced obese-insulin-resistant rat models

Methods

Male Wistar rats (n=10) were continually fed with HFD and treated with either vehicle (HFV, virgin oil for 2 ml/kg/day, p.o., n=5) or Cyclosorus terminans (HFC, 100 mg/kg/day, p.o., n=5) for 12 weeks. Rats fed a normal diet (NDV, n=5) were used as a control to confirm the development of HFD-induced obesity. The left ventricular ejection fraction (LVEF) and the ratio between early (E) and late atrial (A) ventricular filling velocity were measured using echocardiography, and the homeostatic model assessment for insulin resistance (HOMA-IR) was determined using blood serum. The cardiac tissue was processed to assess mitochondrial reactive oxygen species (ROS) levels, membrane potential (MMP) changes via red/green fluorescence intensity ratio, and apoptotic protein.

Results

HFV rats became obese and had impaired cardiometabolic function as shown by reducing LVEF, E/A ratio, and increasing HOMA-IR, respectively (Fig. 1A-C). These obese rats also had mitochondrial ROS overproduction, MMP depolarization (reduced red/green ratio), and apoptosis (increased Bax protein expression) (Fig. 1D-F). Treatment with Cyclosorus terminans (HFC) significantly mitigated mitochondrial dysfunction and apoptosis, resulting in cardiometabolic protection in HFD-fed rats (Fig. 1A-F).

Conclusion

A new natural product derived from Cyclosorus terminans effectively protected the heart against long-term HFD-induced cardiometabolic impairments by reducing mitochondrial dysfunction and apoptosis. These findings demonstrate Cyclosorus terminans as a novel cardiometabolic protection against obesity-related cardiac complications.
Relationship between obesity and hypertrophic or dilated cardiomyopathy: the role of sex
Authors: Antonopoulos A , Panagiotopoulos I , Terentes-Printzios D , Omer M , Mentias A , Lazaros G , Tsioufis K , Elgendy I , Vlachopoulos C
Published: October 2024

Background

Evidence suggests an association between obesity and the risk for cardiomyopathy development, however robust evidence is still lacking. In this study we sought to explore the relationship of obesity with hypertrophic (HCM) and dilated cardiomyopathy (DCM) and possible interactions with sex using large scale epidemiological real-world data.

Methods and Results

We analyzed data from the Nationwide Inpatient Sample (NIS) of U.S. hospitalizations for the years 2015-2019. There were a total of n=46,934 admissions with a diagnosis of HCM and n=170,924 with DCM. There was a significant interaction between cardiomyopathies’ diagnosis with sex and age subgroups; the rates of both DCM and HCM increased with age (p<0.001 for both); DCM diagnosis was significantly higher in males compared with females (0.85% vs. 0.35%, p<0.001). After adjustment for age, sex, race, and presence of arterial hypertension there was a significant stepwise positive association between obesity and the population rates of both cardiomyopathy subtypes. For hospitalized patients with a body mass index (BMI) ≥30kg/m2 there was an odds ratio (OR) of 1.68 (95%CI: 1.55-1.81, p<0.001) for HCM andOR=1.82 (95%CI: 1.79-1.84, p<0.001) for DCM. More importantly, the positive relationship between a cardiomyopathy diagnosis (HCM or DCM) with increasing BMI was driven by the male sex (p<0.001 for both) and it was non-significant in females.

Conclusions

The findings from this nationwide observational analysis support a sexual dimorphism in the relationship between obesity and hypertrophic or dilated cardiomyopathy, which should be further investigated.Cardiomyopathy-obesity
Activation of fibroblast growth factor 21 by Canagliflozin reduces high-fat diet associated obesity-related cardiac injury: a translational study from bench to bedside
Authors: Liu P Y , Vairaperumal T , Lee Y T , Tsai T Y
Published: October 2024

Aims/hypothesis

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes, and evidence shows that they may confer a cardioprotective effect to reduce the incidence of cardiovascular conditions in obese type 2 diabetes patients. The mechanisms underlying this effect remain unclear, but an SGLT2i, canagliflozin (CANA), has been reported to increase levels of fibroblast growth factor-21 (FGF21) and enhance activation of its downstream target proteins. We thus aimed to study whether the effect on FGF21 by CANA can reduce obesity-related cardiac injury.

Methods

1) Animal study: Sixteen-week-old normal diet and high-fat diet male mice were treated with or without 30 mg/kg CANA once a day for 24 weeks, and were subsequently examined for body weight, blood glucose levels, adipose tissue changes, lipid accumulation in the liver, and cardiac function.

2) Cell study: An in vitro study that treated H9c2 cardiomyocyte cells cultured in a simulated high-lipid environment containing palmitic acid (PA) with FGF21 recombinant protein was also conducted to examine protein expression profiles. Furthermore, the effect of CANA on FGF21 expression.

3) Human clinical trial: A randomized double-blinded control trial (NCT 05764811) was performed to test effect of CANA on MRI liver fibrosis scores of obese type 2 diabetes patients (n = 40).

Results

1) High-fat diet mice treated with CANA for 24 weeks had lower average body weight than untreated controls (34 g vs. 40 g, p < 0.001). In addition, CANA treatment stimulated FGF21 protein production in liver tissue and plasma at higher levels for both normal diet and high-fat diet mice, and reduced expression levels of proteins associated with fibrosis and apoptosis.

2) H9c2 cardiomyocyte culture studies suggested that a simulated high-lipid environment with PA caused higher expression of apoptotic proteins, but the addition of FGF21 recombinant protein significantly reduced apoptosis signalling. 3) MRI before and after 4 weeks of CANA treatment in obese type 2 diabetes patients showed a significant reduction in liver fibrosis scores for those receiving CANA treatment.

Conclusion

CANA treatment stimulated FGF21 protein expression and reduced fibrosis and apoptosis signalling protein expression. Moreover, reductions in liver fibrosis scores were observed in obese type 2 diabetes patients treated with CANA. Taken together, this suggests that CANA-induced FGF21 expression may exert a cardioprotective effect against fibrosis and apoptosis and can potentially reduce the risk of obesity-related cardiac injury.
Circadian heart rate fluctuations predict 21-year cardiovascular and all-cause mortality in type 2 and type 1 diabetes
Authors: Nesti L , Chiriaco M , Sacchetta L , Moriconi D , Santoni L , Forotti G , Chiriaco G , Natali A , Solini A , Trico D
Published: October 2024

Background

Alterations in circadian heart rate (HR) fluctuations have been associated with cardiovascular events in the general population. This study aimed at defining their long-term prognostic value for cardiovascular and all-cause mortality in patients with diabetes.

Methods

We examined a cohort of 349 patients with type 2 or type 1 diabetes (52% women, age 57.1±11.9 years, BMI 29.4±5.9 kg/m2, HbA1c 8.6±2.1%, 81% type 2 diabetes) who underwent 24h ambulatory blood pressure and HR monitoring (ABPM) and assessment of diabetic microvascular complications. The median standard deviation (SD) value of ABPM-derived HR measurements was used to define patients with low daily HR fluctuations (low 24h-HR SD), while a <10% decline in average night-time vs day-time HR identified patients with blunted nocturnal HR dip (n=107, 31%). The clinical features and time-dependent prognostic impact of these conditions were evaluated over a 21-year observational follow-up.

Results

Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and high prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years of follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. After adjustment for potential confounders, the low 24h-HR SD group had a higher risk for both cardiovascular (hazard ratio 1.99, 95% CI 1.29–3.06, p=0.002) and all-cause mortality (hazard ratio 1.50, 95% CI 1.03–2.18, p=0.033), compared with high 24h-HR SD. Consistently, patients with blunted nocturnal HR dip had a higher adjusted risk for cardiovascular (1.61, 95% CI 1.07–2.43, p=0.023) and all-cause mortality (1.61, 95% CI 1.11–2.34, p=0.012), compared with those with preserved nocturnal HR dip.

Conclusions

Impaired circadian HR fluctuations are frequent in patients with long-standing diabetes and are associated with microvascular disease and increased long-term cardiovascular and all-cause mortality. Identifying these conditions via 24h-ABPM may provide a cost-effective risk stratification tool in this high-risk population.Kaplan-Meier curves
Association between normal range UACR and insulin resistance and prediabetes among US adults:
Authors: Wu S , Yang Y , Zhu J
Published: October 2024

Background

Recent studies have shown that urine albumin-to-creatinine ratio (UACR) within the normal range is associated with increased risk of hypertension, diabetes, cardiovascular death and all-cause death. However, the relationship between normal range UACR and the prevalence of insulin resistance (IR) and prediabetes has not been explored.

Methods

The study included 14,208 US adults with normal range UACR values and without diabetes from the National Health and Nutrition Survey (1999-2018). The outcome variables included IR and prediabetes, as defined by the 2013 American Diabetes Association guidelines. The weighted multivariate linear regression, weighted multivariate logistic regression, restricted cubic spline (RCS) regression, and subgroup analysis were conducted to examine the relationship of UACR with IR and prediabetes.

Results

The weighted multivariate linear regression analysis showed that a 1-standard deviation (SD) increment in ln (UACR) was positively associated with fasting plasma glucose (FPG) (β = 0.02, 95% CI: 0.01, 0.04), glycosylated hemoglobin (β = 0.01, 95% CI: 0.00, 0.02), fasting serum insulin (FSI) (β = 0.50, 95% CI: 0.31, 0.68), and homeostasis model assessment of insulin resistance (HOMA-IR) (β = 0.14, 95% CI: 0.09, 0.19). The weighted multivariate logistic regression analysis revealed that a 1-SD increment in ln (UACR) was significantly associated with an increased prevalence of prediabetes (OR = 1.10, 95% CI: 1.04-1.15), but not with IR (OR = 1.05, 95% CI: 0.99-1.12). With the lowest quartile of UACR as a reference, ORs (95% CIs) for IR in the second, third, and fourth quartiles were 1.10 (0.86, 1.15), 1.15 (0.98, 1.33), and 1.12 (0.95, 1.32), respectively, and ORs (95% CIs) for prediabetes were 1.35 (1.19, 1.52), 1.32 (1.14, 1.53), and 1.44 (1.24, 1.66), respectively. Subgroup analysis indicated that smoking had a significant impact on the association between UACR and prediabetes. The association between UACR and prediabetes was more significant in smokers than in non-smokers (P for interaction = 0.03). RCS regression analysis revealed a non-linear positive dose-response association between UACR and indicators of diabetes.

Conclusion

Elevated UACR, even within the normal range, was positively associated with indicators of diabetes and increased prevalence of prediabetes among US adults. Smoking had a significant impact on the association between UACR and prediabetes, with a more pronounced association observed among smokers.uacr with diabetes markersUacr with ir and prediabetes
Prognostic outcomes of masld and obesity in acute myocardial infarction
Authors: Kong G , Koh J , Wong E , Zhang A , Ping C , Yeo T C , Yip J , Foo R , Chan M Y , Loh P H , Chew N W S
Published: October 2024

Background

Patients with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) have an increased risk of cardiovascular disease. This study seeks to examine the prognostic significance of obesity and MASLD in patients presenting with acute myocardial infarction (AMI).

Methods

This study compared the clinical characteristics and outcome of patients with and without obesity and MASLD at a tertiary centre in Singapore. Patients were stratified by their obesity and MASLD statuses into four groups. Obesity was defined as BMI ≥27.5. MASLD was defined as hepatic steatosis, which was determined using Hepatic Steatosis Index, and at least one of the five metabolic criteria. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality, adjusted for age, sex, ethnicity, previous AMI, AMI type, and left ventricular ejection fraction.

Results

A total of 5702 patients with AMI were included in this study. Among the cohort, 3803 were non-obese and without MASLD, 343 were non-obese with MASLD, 638 were obese without MASLD, and 918 were obese with MASLD. The mean follow-up duration was 3.1 ± 2.4 years. Non-obese patients with MASLD were most likely to develop complications of heart failure, cardiogenic shock, and stroke. On 30-day follow-up, there were no significant differences in all-cause mortality (p=0.312). However, on long-term follow-up, non-obese MASLD patients had the highest mortality (9.6%, p=0.019). After adjusting for confounders, patients who were non-obese with MASLD, and patients who were obese with MASLD, remained independently associated with higher long-term all-cause mortality (HR 1.400, 95% CI 1.077-1.820 and HR 1.222, 95% CI 1.005-1.485 respectively), with non-obese patients without MASLD as the reference.

Conclusions

This study demonstrates that regardless of obesity status, patients with MASLD have poorer outcomes in AMI. With its high metabolic burden, it is important to identify patients with MASLD for risk stratification and targeted treatment.Adjusted long-term all-cause mortality
Twelve-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus
Authors: Ikonomidis I , Katogiannis K , Kountouri A , Pavlidis G , Thymis J , Korakas E , Kostelli G , Katsanaki E , Michalopoulou E , Vlachomitros D , Pliouta L , Balampanis K , Lambadiari V
Published: October 2024

Background

Individuals diagnosed with type 1 diabetes mellitus (T1DM) exhibit indications of vascular and endothelial dysfunction earlier in comparison to healthy individuals. Evidence shows that SGLT-2 inhibitors (SGLT-2i) have a beneficial impact on cardiovascular health in individuals with type 2 diabetes mellitus (T2DM). We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM.

Methods

We recruited in total 40 patients with T1DM and pour glycemic control who were treated with insulin and received dapagliflozin (n=20) or intensification of insulin treatment (n=20) (control group). We measured at baseline and at twelve months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography.

Results

At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p>0.05). After 12 months of treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−16%, p<0.05), in PWV (−9.3%, p<0.05), in cSBP (−6%, p<0.05) and in GLS (+4%, P<0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +0.4%, PWV: -1%, cSBP: −2%, GLS: −1% at 4 months, P>0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after one year treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P<0.05).

Conclusions

Twelve months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control.