bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender differences in depression after acute coronary syndromes
Authors: Mangas Palma P P , Moreira H M , Rocha M R , Pinho A P , Oliveira C O , Marques C M , Cabrita A C , Rodrigues J R , Afonso Rocha A F , Dias P D , Rodrigues R R 
Published: June 2024

Abstract

Introduction
After an acute coronary syndrome (ACS), a considerable number of patients experience clinically significant depressive symptoms. The prevalence of major depressive disorder ranges from 20 to 30% and is a well-established risk factor for adverse cardiovascular (CV) outcomes and mortality. Depression complicates the optimal management of CV disease by worsening CV risk factors and decreasing adherence to healthy lifestyles and evidence-based medical therapies (1,2).

Purpose
To characterize gender differences in depressive symptoms in patients enrolled in a cardiac rehabilitation program (CRP) after an ACS.

Methods
We performed a retrospective single-centre cohort study which included patients who were referred to our CRP from 2009 to 2018 after an ACS. Evaluation of depressive symptoms was performed using the self-administered Hospital Anxiety and Depression Scale (HADS) before and 12 months after the end of the CRP. Quality of life was evaluated using the EuroQol-5D Questionnaire. We used multiple linear regression to identify variables that made an important contribution for HADS score and to adjust for confounding variables.

Results
A total of 466 patients were included (75.6% male, with a mean age of 54.4 + 9.62 years). Women were more likely to have major depressive disorder (12.7% vs 5.80%, p=0.033) and less likely to have hypertension (60.6% vs 78.2%, p&lt;0.001), diabetes (7.70% vs 16.3%, p=0.024) or to smoke (60.6% vs 78.2%). At the baseline evaluation, women had a higher mean HADS-Depression score (6.60 vs 5.25, p=0.009) and lower EuroQol-5D score (0.85 vs 0.92, p&lt;0.001). Other baseline characteristics were similar between the groups. During the CRP, women were referred more frequently for psychotherapy (50.0% vs 48.5%, p=0.002) and attendance was similar between the groups.
After 1 year of follow-up, women had a mean HADS-Depression score higher than baseline, while men had a decrease on the mean score (0.83 vs -0.24, p=0.03). Multiple linear regression analysis revealed that female gender was a significant predictor of the of HADS-Depression score after adjustment for age, previous diagnosis of major depressive disorder, antidepressant medication and diabetes (β=1.26, 95% confidence interval 0.14-2-38, p=0.027).

Conclusion
Female gender was associated with depression after ACS, independent of all relevant risk factors. New strategies are needed in CRPs, including tailored interventions, mental health support and education, in order to improve quality of life and improve gender disparities.
Does the relationship between time-varying achieved HbA1c and risk of coronary events depend on haptoglobin phenotype within the Action for Health in Diabetes (Look AHEAD) study?
Authors: Carew A , Warren R A , Bancks M P , Espeland M A , Bahnson J L , Lewis C L , Levy A P , Sapp J L , Urquhart R , Wang J L , Rimm E B , Cahill L E 
Published: June 2024

Abstract

Background
Our previous research has identified the haptoglobin (Hp) phenotype as a potential biomarker that could be used to personalize glycemic control in type 2 diabetes mellitus (T2DM) to prevent coronary artery disease (CAD), the most common cardiovascular disease (CVD). We observed that attaining HbA1c ≥8.0% compared with 7.0–7.9% was consistently associated with incident CAD risk among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with the Hp2-2 type(1). No similar association was observed among participants without the Hp2-2 type. However, most ACCORD participants were middle-aged and older males who were at high risk of CVD. Therefore, the optimal glycemic target for CAD prevention for the Hp types remains unclear among women, younger adults, and those at lower risk of CVD.

Objective
To explore the relationship between achieving specific clinically relevant HbA1c targets and risk of incident CAD in separate Hp types in a diverse cohort of individuals living with T2DM (the Action for Health in Diabetes (Look AHEAD) study(2)).

Methods
Hp type was measured in 4,539 blood samples from the Look AHEAD study using a validated assay. Cox regression models with time-varying covariables were used to quantify the association between time-varying achieved HbA1c (&lt;6.5%, 6.5-6.9% and ≥8.0% compared to 7.0-7.9%), updated at years 1-4 and biennially thereafter, and incident CAD in the Hp2-2 (n=1,590) and non-Hp2-2 (n=2,949) types separately. Further pre-specified subgroup analyses by age, sex, and history of CVD were performed in each Hp type group separately.

Results
During 16 years of follow-up, 744 incident CAD cases were documented. Compared with HbA1c 7.0-7.9%, having HbA1c &lt;6.5% was associated with a 29% lower CAD risk among participants with the non-Hp2-2 type (adjusted HR 0.71, 95% CI 0.55-0.90). In subgroup analyses, this association was present in participants with the non-Hp2-2 type who were male (0.58, 0.42-0.80), who did not have a history of CVD (0.67, 0.49-0.93), and who were aged ≥65 years at baseline (0.64, 0.43-0.95). HbA1c ≥8.0% was associated with CAD risk among participants with the Hp2-2 type who had a history of CVD (1.81, 1.02-3.21). No associations were observed between the other HbA1c targets and CAD risk when Hp2-2 participants were combined or partitioned into subgroups.

Conclusion
Achieving HbA1c &lt;6.5% compared with 7.0–7.9% reduced the risk of CAD events in Look AHEAD participants with the non-Hp2-2 type, but not in participants with the Hp2-2 type. HbA1c ≥8.0% was associated with higher CAD risk among participants who had the Hp2-2 type and a history of CVD.
A high level of cardiorespiratory fitness is associated with a stiffer spleen in a population-based cohort study
Authors: Manteufel E , Kaczmarek S , Lehnert K , Markus M , Ewert R , Stubbe B , Ittermann T , Friedrich N , Tzschaetzsch H , Meyer T , Sack I , Doerr M , Bahls M 
Published: June 2024

Abstract

Background
Higher cardiorespiratory fitness (CRF) and muscle strength are independently associated with reduced risk of cardiovascular disease and morbidity. Higher CRF and muscle strength are also associated with an improved immune response. Since the spleen plays an integral role in the innate and adaptive immune system, we hypothesized that CRF and muscle strength would be associated with biophysical characteristics of the spleen. We related CRF and muscle strength with spleen stiffness as measured by shear wave elastography in a large population-based cohort from the Study of Health in Pomerania (SHIP).

Methods
We used cross-sectional data from 677 participants of the population-based, prospective Health Study in Pomerania (SHIP-START-4). A symptom-limited cardiopulmonary exercise test was performed according to a modified Jones protocol. Hand grip strength was determined using a JAMAR dynamometer. Time-harmonic elastography was used to measure splenic shear wave velocity as a surrogate for splenic stiffness. The shear waves in the spleen were generated by a loudspeaker integrated into an examination table, which emitted multifrequency vibrations in the range of 27 to 56 Hz. Tissue strain was encoded from radiofrequency data acquired by an ultrasound system. Shear wave velocity maps covering the entire visible spleen in B-mode were calculated using the k-MDEV method. Finally, mean values were calculated within a manually drawn region of interest. We used linear regression models adjusted for age, sex, and body weight to relate CRF and muscle strength to spleen shear wave velocity.

Results
The median age of the study population was 61 (25th quartile: 52 and 75th quartile: 70) years and 54% were women. A one liter/min higher VO2peak was associated with a 0.05 (95% confidence interval [CI] 0.01 - 0.07; p &lt; 0.01) m/s higher splenic shear wave velocity. A 100 watt higher peak workload was also associated with a 0.05 (95% CI 0.01 - 0.08, p &lt; 0.01) m/s higher splenic shear wave velocity. When CRF was normalized to body weight, a 1 ml/kg/min higher CRF was associated with a 0.007 (95% CI 0.005 - 0.009, p &lt; 0.01) m/s higher splenic shear wave velocity. We found no associations between hand grip strength and splenic shear wave velocity.

Conclusions
In our study, we found that higher VO2peak, VO2peak adjusted for body weight and maximal workload were associated with higher spleen stiffness. As a non-invasive and inexpensive test, time-harmonic shear wave elastography has potential for patient care. Interestingly, there seems to be no correlation between muscle strength and splenic shear wave velocity. It remains unclear why CRF, but not muscle strength, is related to splenic shear wave velocity.
Blood pressure assessment, treatment and control for primary prevention of cardiovascular disease in patients with and without depression
Authors: Ellins E , Summers R , Akbari A , Lloyd K , Osborn D , John A , Gravenor M , Halcox J 
Published: June 2024

Abstract

Background
Patients with depression are at increased risk of future cardiovascular disease (CVD) events compared to those without depression. The reasons for this are not fully understood. Appropriate management of CVD risk factors, including blood pressure (BP) are essential for primary prevention of CVD.

Purpose
To explore whether there are differences in the likelihood of assessment, treatment and attainment of target levels of BP in patients with depression compared to those without.

Methods
A retrospective observational cohort study of patients without a history of depression or CVD was conducted using individual-level linked electronic health record data between 2010 & 2019 using the all-Wales SAIL Databank. Clinical codes were used to identify depression and hypertension diagnoses, BP assessments and antihypertensive therapy (AHT) from general practice (GP) data. Blood pressure assessment is presented as person year rates, and logistic regression was used to identify the likelihood of treatment and control of BP (&lt;140/&lt;90mmHg).

Results
A total of 2,290,075 patients were included (47% female & 7.7% depressed). Depressed patients were younger than non-depressed (mean age 32.0±15.5 vs 40.7±19.3 yrs respectively). Blood pressure assessment rates (BP checks per person per year) were greater in patients with depression 0.813 (0.811-0.815) vs 0.621 (0.620-0.621). Assessment was most frequent in depressed women (0.988 [0.985-0.991]) and least in non-depressed males (0.490 [0.489-0.490]). In patients with a history of HTN, GP diagnosis or high BP reading (n=738,164), 265,232 (35.9%) were on AHT within one year; a smaller proportion of depressed patients with hypertension were receiving AHT than non-depressed (23,808 [34.0%] vs 241,424 [36.1%] p&lt;0.001). However, after multiple logistic regression (adjusting for age, sex, location of residence, deprivation, and comorbidities), depressed patients were more likely to be on AHT (OR 1.22 95%CI 0.12-1.32). In those patients on AHT 235,134 (88.7%) had at least one valid BP measurement during the year. Of these 114,601 (48.7%) achieved a BP &lt;140/90 mmHg. A greater proportion of depressed patients with hypertension on AHT had documented control of BP than non-depressed (11,143 [57.3%] vs 103,458 [48.0%] p&lt;0.001 OR 1.28 95%CI 1.11-1.50). There was a significant interaction between depression and sex, with depressed females being the most likely to achieve control (p&lt;0.001).

Conclusion
Patients with depression are more likely to have BP assessed and to have hypertension treated and controlled than patients without depression within Welsh primary care. This maybe due to more frequent interaction with their GP, but further research is required to investigate reasons and impact on outcomes.
Heterogeneous associations of traditional atherosclerotic risk factors and long-term complications in different arterial territories: the EPIC Norfolk prospective population cohort
Authors: Van Den Bogaart M , Van Trier T J , Snaterse M , Martens F M A C , Peters R J G , Boekholdt S M , Jorstad H T 
Published: June 2024

Abstract

Background
Atherosclerotic risk factors have been associated with cardiovascular disease (CVD) complications in specific arterial territories. However, these observations are limited by relatively short-term follow-up (i.e. ten years) We therefore investigated longer-term associations between atherosclerotic risk factors and specific cardiovascular complications in a large cohort with ≥20 years follow-up.

Methods
We included participants from the EPIC Norfolk prospective population cohort without a history of CVD. The strength of associations between CVD risk factors (smoking, low-density lipoprotein cholesterol (LDL-c), and systolic blood pressure (SBP)) and CVD events were evaluated using a competing risks regression model. CVD events were defined as hospitalization or death due to ischemic heart disease (IHD), ischemic stroke, hemorrhagic stroke or peripheral arterial disease (PAD) including abdominal aortic aneurysm (AAA). Patients were followed-up until the first event, death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, diabetes, HDL-c, kidney function and body mass index. LDL-c and SBP were analysed by comparing highest versus lowest quartiles. Smokers (at baseline) were compared to never-smokers. For 10.1% of participants with missing risk factor data, median imputation was used.

Results
We included 23,581 participants (56% women) with a mean baseline age of 58 (IQR 51-66). During mean follow up of 22.4 years (IQR 19-23), occurrence of any CVD event was observed in 29.4% (6,926) individuals. Of these, 55.3% (4,449) were IHD, 15.0% (1,211) were ischemic stroke, 5.9% (471) were hemorrhagic stroke and 23.8% (1,920) were PAD or AAA. LDL-c was strongly associated with IHD [adjusted hazard rate (aHR) 1.67, 95% CI 1.50 - 1.85], but not significantly with hemorrhagic stroke (aHR 1.07, 95% CI 0.78 – 1.47). SBP was significantly associated with ischemic stroke (aHR 1.94, 95% CI 1.53 – 2.46), but not with hemorrhagic stroke (aHR 1.39 95% CI 0.97 – 2.00). Smoking was strongly associated with PAD/AAA (aHR 2.49, 95% CI 2.13 - 2.92), but not with ischemic stroke (aHR 1.20, 95% CI 0.95 – 1.51) and hemorrhagic stroke (aHR 1.20 95% CI 0.83 – 1.73) (Figure 1).

Conclusions
There is considerable heterogeneity in the associations between atherosclerotic risk factors and long-term cardiovascular complications in different arterial territories. Knowledge of these differences may assist in personalised treatment decisions and risk communication. Hazard Ratios for CVD events.
Statin therapy eligibility in a large primary prevention cohort according to European Society of Cardiology Guidelines
Authors: Hauguel-Moreau M , Mansencal D , Miliani K , Beauchet A , Rodon C , Dubourg O , Mansencal N 
Published: June 2024

Abstract

Background
2016 European Society of Cardiology (ESC) guidelines on statin therapy eligibility in primary prevention were updated in 2021, with significant differences and particularly the use of a new estimation of 10-year fatal and nonfatal CVD risk with Systematic Coronary Risk Estimation 2 (SCORE2).

Purpose
The aim of the study was to compare the proportion of subjects aged 40 to 69 years eligible to statin therapy according to the 2016 and 2021 ESC recommendations in a large primary prevention cohort.

Methods
We conducted a screening campaign between January 2007 and December 2022 for cardiovascular risk factors in large urban cohort of subjects aged 40-69 (the CARVAR 92 study). We systematically calculated the individual cardiovascular risk for all our subjects. We thus estimated the proportion of subjects eligible for statin therapy based on 2021 ESC guidelines versus 2016 ESC guidelines. Costs relating to statin therapy were also estimated.

Results
27,807 subjects were included in the CARVAR 92 study: 13.7% were eligible to statin therapy according to the 2016 ESC guidelines versus 32.2% according to the 2021 guidelines (p &lt; 0.0001). The proportion of subjects eligible to statin therapy increased by a factor 2.3 between the 2016 and 2021 ESC guidelines for the whole cohort, and increased by a factor 12 in men aged 40 to 50 (from 3.8% of individuals eligible to statin therapy for 2016 recommendation to 45.7% [p &lt; 0.0001] for 2021 recommendation). Costs associated with statin therapy for the whole cohort increased by a 2.7 factor between 2016 and 2021 recommendations.

Conclusion
In a large primary prevention cohort, we observed a strong increase in the number of subjects eligible to statin therapy with the new 2021 ESC recommendations (versus 2016) and therefore in statin costs, particularly in men between 40 and 50 years old. The clinical and economic impact on the occurrence of cardiovascular events of these new recommendations in a real life remains to be evaluated. Eligibilty to statin therapy.
The effect of atorvastatin on mevalonate levels in blood plasma in patients with coronary heart disease and muscle side effects
Authors: Lauritzen T , Munkhaugen J M , Lindahl S H L , Bergan S B , Peersen K P , Husebye E H , Vethe N T V 
Published: June 2024

Abstract

Background
Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in the mevalonate biosynthesis pathway. By this mechanism, the synthesis of cholesterol is reduced as well as the synthesis of isoprenoid intermediates, which are essential to the isoprenylation of several proteins. Decreased protein isoprenylation has been suggested as a potential pathophysiological mechanism of statin intolerance, but in-vivo studies remain to be conducted.

Purpose
To assess whether mevalonate levels in blood plasma, in response to atorvastatin treatment, are associated with statin intolerance in patients with coronary heart disease (CHD).

Methods
In 2019, 71 CHD patients with self-perceived statin-associated muscle symptoms (SAMS) during atorvastatin therapy were randomized to double-blinded treatment with atorvastatin 40 mg/day and matched placebo in a crossover design. Based on predefined criteria, 20 patients reported more symptoms on atorvastatin than placebo whereas 51 patients showed no difference in muscle symptom intensity. During a 7-months-open-label follow-up period, two research cardiologists attempted to reintroduce statin treatment at the highest tolerable dose. Seven out of 71 patients (10%) were clinically intolerant to statins, i.e. not tolerating ≥3 different statins due to myalgia with no or minor increase in creatine kinase. The remaining 64 patients were statin-tolerant. Mevalonate in blood plasma was measured with LC-MS/MS.

Results
Mean age was 65 (SD 9) years, and 32% were female. There was no significant difference in mevalonate levels in blood plasma between statin intolerant (n=7) and tolerant (n=64) patients (median 39 vs 32 nmol/L, p=0.51). The statin-intolerant patients had a minor reduction in mevalonate on atorvastatin treatment compared to the statin-tolerant (Figure). Absolute differences in mevalonate were median -8.1 nmol/L vs. -24.3 nmol/L (p=0.04), and relative differences were median -9.7% vs -40.9% (p=0.04) for the intolerant vs the tolerant group.

Conclusion
CHD outpatients intolerant to 3 or more statins had a less pronounced reduction in mevalonate levels in blood, during intake of atorvastatin, compared to statin tolerant patients. Statin-induced mevalonate reduction does not seem to be the cause of statin intolerance. Further studies are needed to clarify the role of mevalonate in patients with statin side effects. Mevalonate differences.
High Lp(a) levels are a potential risk factor for aortic valve interventions in patients with bicuspid aortic valve
Authors: Arsanjani R , Farina J M , Pereyra M , Kamel M A , Abbas M T , Scalia I , Mahmoud A K , Baba Ali N , Ayoub C , Sell-Dottin K , Alsidawi S , Lester S , Barry T , Majdalany D S , Marcotte F 
Published: June 2024

Abstract

Background
Bicuspid aortic valve (BAv) is associated with increased oxidative stress and inflammation, resulting in valve fibrosis, calcification, and ultimately early degenerative valve disease, often necessitating premature aortic valve intervention. In recent years, growing evidence has been published supporting the role of lipoprotein(a) [Lp(a)], an important carrier of oxidized phospholipids, in the development of aortic valve disease in the general population. However, the specific influence of Lp(a) levels in patients with BAv remains to be firmly established.

Purpose
To assess the role of Lp(a) levels in the development of aortic valve disease and the necessity for aortic valve interventions among individuals with BAv.

Methods
This retrospective multicenter study encompassed consecutive patients diagnosed with BAv from January 1997 to December 2022, all of whom had undergone serum Lp(a) measurement. This study evaluated the association between Lp(a) concentrations and the occurrence of aortic valve interventions. A cutoff point of ≥30 mg/dl for high Lp(a) levels was established. Binary logistic regression was utilized to calculate the odds ratio (OR) for an aortic intervention according to high versus low Lp(a) levels. Additionally, Kaplan Meier curves were employed to estimate the cumulative requirement for an aortic valve replacement based on Lp(a) concentrations.

Results
A total of 452 patients with BAv and a Lp(a) measurement were included in the study, with a mean age of 37.2 ±10.5 years at the time of BAv diagnosis, with 71.2% being male. Among these, 101 (22.3%) patients underwent an aortic valve replacement. In 72 cases (71.3%) aortic stenosis was the primary indication for intervention, while aortic regurgitation accounted for 29 cases (28.7%). The presence of elevated Lp(a) levels (≥30 mg/dl) demonstrated a significant association with the requirement for an aortic valve intervention (OR 2.2, 95%CI 1.4-3.6, p&lt;0.001) in both the regression analysis and using the Kaplan-Meier estimator (Figure). High Lp(a) concentrations posed a risk factor for aortic valve replacements regardless of whether the primary indication for intervention was significant stenosis (OR 1.8, 95%CI 1.1-3.1, p=0.028) or regurgitation (OR 2.5, 95%CI 1.2-5.4, p=0.018).

Conclusion
Increased concentrations of Lp(a) may influence the clinical trajectory of patients with a BAv and may be a significant risk factor for aortic valve replacement, irrespective of the primary indication for intervention. Further investigations will be critical in unveiling the precise pathological mechanisms of Lp(a) in BAv. Confirming whether reducing Lp(a) levels could slow the progression of aortic disease in this demographic requires further exploration. Kaplan-Meier estimator.