bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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<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.
A polyphenol-rich active substance (TOTUM-070) lowers LDL-cholesterol in subjects with moderate hypercholesterolemia. The OLALIP study
Authors: Otero Y , Sirvent P , Langhi C , Bargetto M , Sapone V , Flageul O , Le Guicher G , Pickering G , Macian N , Cazaubiel M , Peltier S , Bard J M
Published: June 2024

Background/Introduction

Hypercholesterolemia is a major risk factor for cardiovascular diseases. Some polyphenols have shown promising potential in modulating circulating cholesterol. The polyphenol-rich active substance TOTUM-070 (T070) is a blend of five plant extracts that have previously demonstrated beneficial effects in preclinical models, and in subjects with moderate hypercholesterolemia when used at 5g/day for 12 weeks (the HEART study NCT04760951).

Purpose

The OLALIP study is an open-label, single-centre, single-arm, clinical trial designed to assess the effects of consuming TOTUM-070 at 2.5g/day for 6 weeks on lipid metabolism in individuals at an increased cardio-metabolic risk.

Methods

Thirty-one subjects were recruited, including men and women aged 18 to 70 years, with a BMI ranging from 18.5 to 35 kg/m2, and moderate hypercholesterolemia not requiring immediate pharmacological lipid-lowering treatment. The subjects received a daily dose of 2.5g of T070, divided into two administrations (BID), for 6 weeks. The primary outcome was to evaluate the effect of T070 on LDL-cholesterol (assessed by Friedewald formula). Secondary outcomes included the effects on total cholesterol (TC), HDL-cholesterol, non-HDL cholesterol, triglycerides, Apo-A1, Apo-B and free fatty acids (FFA).

Results

A total of 31 subjects completed the study (21 males and 10 females; age: 48.9 ± 11.5 years; BMI 26.6 ± 2.9 kg/m2). After 6 weeks of supplementation, LDL-cholesterol decreased by 10% (1.31 ± 0.2 vs 1.46 ± 0.2 g/L at baseline, p<0.0001). In a subpopulation of subjects with a baseline LDL-cholesterol level ≥ 1.3 g/L (n=23), the reduction in LDL-cholesterol reached 13% (p<0.0001). Moreover, 96% of the subjects in this subpopulation presented reduced LDL-cholesterol levels after 6 weeks of T070 supplementation. Among the secondary outcomes, there was a decrease in TC (-8%, p<0.0001), non-HDL cholesterol (-11%, p<0.0001), Apo B (-7%, p<0.05) at the end of the supplementation period. HDL-cholesterol was not significantly modified.

Conclusion

The polyphenol-rich active substance T070 showed beneficial effects on hypercholesterolemia when administered at a daily dose of 2.5g for 6 weeks. This represents half the dose and duration of previous studies, highlighting the relevance of using T070 in the management of hypercholesterolemia.
Unlinking sudden death from coronary artery disease - a systematic scoping review of the association of low-density lipoprotein cholesterol and sudden death
Authors: Beyer R E , Parekh S N , Inigo J D , Chitroceanu A M , Day G R , Koehler A , Simpson Jr R J
Published: June 2024

Background

Sudden death (SD) is a common first manifestation of cardiovascular disease (CVD) and accounts for more than 350 000 deaths per year in the U.S. (1) Coronary artery disease is held accounted for up to 80% of SD cases. (2) Whilst low-density lipoprotein (LDL-c) is a major modifiable risk factor for atherosclerosis and CVD, (3) it is still unclear whether elevated LDL-c is associated with SD. Recent studies found conflicting results, (4,5) challenging our understanding of the pathogenesis of SD.

Purpose

To address this apparent paradox for the association of LDL-c with sudden death and to investigate the role of this risk factor in SD, we performed a systematic scoping review of the literature reporting on LDL-c and SD.

Methods

Our review followed PRISMA-Scr guidelines. A comprehensive search string was developed at the guidance of an experienced librarian. Two independent reviewers screened PubMed and EMBASE for peer-reviewed case-control and cohort studies with LDL-c as an exposure variable, and SD as outcome variable. Articles were reviewed in a two-step process of (a) title and abstract screening and (b) full-text screening. Disagreements were resolved through consensus.

Results

Of 1835 articles retrieved, 570 met screening eligibility criteria. Studies that did not include LDL-c as exposure and SD as outcome or did not provide effect sizes were removed. We identified 9 relevant studies from 1982 to 2015, conducted in the U.S., Europe, and Asia, with a total of 9,639 SD cases. Two studies found an increased risk of SD with higher LDL-c and 2 studies found the contrary. 4 studies did not identify LDL-c as an independent associate of SD. One cohort study found a U-shaped relationship where both higher and lower levels led to higher risk for SD. Spectrum of included study type was broad, and definition of sudden death varied among studies. Results are displayed in Table 1.

Conclusion

Unlike other risk factors for coronary artery disease, LDL-cholesterol does not show a consistent association with sudden death. Focusing solely on lipid reduction may have limited impact on sudden death incidence. This suggests that sudden death may be of more multifactorial nature and require comprehensive strategies for effective prevention.
Do triglycerides impact cardiovascular outcomes? A 10-year follow up study from a Portuguese cohort
Authors: Santos Moreira H , Mangas Palma P , Rocha M , Pinho A , Oliveira O , Santos L , Cabrita A , Marques C , Araujo V , Rocha A , Rodrigues J , Dias P , Lebreiro A , Rodrigues R
Published: June 2024

Introduction

Hypertriglyceridemia has long been described as a marker of increased cardiovascular (CV) risk, but the intricate interplay of triglycerides (TG) and CV events is still a matter of ongoing debate, with previous studies showing controversial data.

Purpose

The aim of this study was to determine whether TG level in very-high risk patients (pts) following acute coronary syndromes (ACS) are associated with major adverse CV outcomes at long-term follow-up (FUP). The primary composite endpoint included all-cause mortality and hospital admissions due to CV events.

Methods

We performed a retrospective analysis of ACS pts, referred to a cardiac rehabilitation program (CRP) after discharge, in our centre, between 2008 and 2018. Comprehensive data including information from index event and posterior FUP was collected through medical records review. Pts were subsequently stratified in two groups according to TG level: group A with TG < 150 mg/dL and group B with TG ≥ 150 mg/dL. Statistical analysis was performed in SPSS software.

Results

A total of 591 pts were enrolled with a predominant male representation (85.3%) and a mean age of 55 ± 10 years old. The most frequent diagnosis at admission was ST segment elevation myocardial infarction (49.6%, 293 pts). Smoking history (77.3%) and hypercholesterolemia (61.6%; p=0.185) were the most prevalent CV risk factors. After the acute phase, all pts underwent CRP, with nutritional support and lipid-lowering therapies intensification, namely high intensity statins. At the end of CRP visits, with a median duration time of 11 (IQR 1) months, 23.2% of pts were included in group B, with a median TG level of 190 (IQR 75) mg/dL. Both groups had comparable demographic and CV features, including a similar metabolic profile with overall median LDL level of 79 (IQR 39) mg/dL (p=0.672). The mean FUP time of our cohort was 10 (± 2) years and was not significantly different between groups A and B (p=0.351). During FUP, 159 (26.9%) pts reached the primary endpoint, mainly at the expenses of recurrent ACS (91 pts, 57%). However, there were no statistically significant differences between groups regarding the occurrence of the primary outcome (122 vs 37 pts, p = 0.972), nor event free survival time (figure 1).

Conclusion

In agreement with some recent trials, our pragmatic study has found no long-term clinical impact associated with TG level in a large cohort of pts with previous ACS, followed for a long period of time. Further large scale randomized controlled trials are needed to comprehensively assess the significance of TG and their targeted therapies in the realm of secondary CV prevention.
The effects of two different exercise protocols in patients with good controlled type 2 diabetes mellitus: proprioceptive exercise vs resistive exercise
Authors: Kaya Aytutuldu G , Subasi F E R Y A L , Akinci B U K E T , Arslan G U L G U N
Published: June 2024

Background

Exercise has benefits on glycemic control, increasing exercise capacity, and muscle strength in patients with type 2 diabetes mellitus (T2DM). In the progression of T2DM, proprioceptive deficits may develop, which can cause inadequate muscle strength and neuropathy. Preventive strategies are needed for T2DM patients without neuropathy even in the early stage of disease. Proprioceptive exercises has a potential to improve dynamic balance through an increase in peripheral sensitivity, and prevent from neuropathy and reduction in falls associated with sensory deficits.

Purpose

To compare the effects of proprioceptive exercise training or resistive exercise training on glycemic control, functional capacity, dynamic balance, sensation and muscle strength in patients with good-controlled T2DM.

Methods

Thirty patients with good-controlled T2DM were randomized into Proprioceptive Training Group (PG) (n=15, mean %glycated hemoglobin (HbA1c)=6.85±0.58, mean age=51.6±8.09/years, 12 F, 3 M) and Resistive Training Group (RG) (n=15, mean %HbA1c= 6.8±1.1, mean age= 50.86±7.51/years, 12 F, 3 M). Fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were analyzed. Functional capacity assessed with six-minute walking test (6MWT) and dynamic balance was evaluated using a dynamic balance system (Prokin PK200 platform). Proprioception sense measured with angle reproduction test in direction of dorsiflexion and plantar flexion and deviation. Cortical sensation was evaluated with two-point discrimination test. Quadriceps and Ankle muscle strength were assessed with a digital hand-held dynamometer (JTech PowerTrack II Commander). All subjects were performed moderate intensity of aerobic exercise 3 times/week for 6 weeks. In addition, patients in PG continued the proprioceptive training for the lower extremities while RG performed moderate intensity lower extremity resistive training 2 times/week.

Results

Significant but not clinically important decrease in HbA1c and FBG were obtained in the groups. Functional capacity, and lower extremity proprioception, cortical sensation and muscle strength showed in-group improvements in both groups. PG also showed significant intragroup improvements in dynamic balance. The groups were similar in terms of obtained changes in all parameters after training (Table 1 and Table 2).

Conclusion

The proprioceptive training leads similar benefits with resistance training on functional capacity and lower extremity sensation, and muscle strength in patients with good-controlled T2DM. Besides, proprioceptive training can be considered to improve dynamic balance.
Effects of reducing sedentary behaviour on cardiac structure and function in adults with metabolic syndrome: a six-month randomised controlled trial
Authors: Norha J , Saarenhovi M , Kallio P , Sjoros T , Garthwaite T , Laine S , Laitinen K , Houttu N , Vaha-Ypya H , Sievanen H , Loyttyniemi E , Vasankari T , Knuuti J , Kalliokoski K K , Heinonen I H A
Published: June 2024

Background

The effects of reducing sedentary behaviour (SB) on cardiac structure and function remain unknown, yet reducing SB may have potential for heart failure prevention.

Purpose

The aim of this study was to investigate whether reducing SB could lead to healthy cardiac remodelling.

Methods

Sixty-four physically inactive adults with metabolic syndrome were randomised into an intervention (n=33) or a control (n=31) group. The intervention group aimed at reducing SB by 1 h/day for six months and increasing non-exercise activities or standing and the control group was advised to continue as usual. All participants wore accelerometers for SB and physical activity (PA) assessment during the whole study. Conventional echocardiographic measurements of cardiac structure and (resting) function were taken before and after the study.

Results

The intervention resulted in a 40 min/day reduction in SB and a concomitant 20 min/day increase in moderate-to-vigorous PA. In the main analyses, no intervention effects on any echocardiographic variable were observed. However, when the participants were re-grouped according to the measured change in SB (i.e., less sedentary group: SB reduction at least 3 %-points [~27 min/day] vs. continuously sedentary group: SB reduction <3 %-points or increase in SB), left ventricular (LV) mass index and LV end-diastolic diameter decreased statistically significantly more in the less sedentary group (group x time p=0.045 and 0.020, respectively; Figure 1). In the whole study group, the change in light PA correlated inversely with the change in LV mass index (r=-0.32, p=0.026). Furthermore, the change in standing correlated with the change in E/e’ ratio (r=0.28, p=0.048).

Conclusion

An intervention aimed at reducing SB by 1 h/day was not sufficient at affecting cardiac structure or function. However, successfully reducing SB may lead to healthy LV remodelling. Figure 1
Physical activity and autonomic function in patients with heart failure: a mediation analysis of functional exercise capacity
Authors: Tanriverdi A , Ozcan Kahraman B , Ozpelit E , Senturk B , Akdeniz B , Yilmaz M B , Savci S
Published: June 2024

Background

Daily physical activity is associated with autonomic nervous system activity in patients with heart failure (1). However, there is a lack of information on whether functional exercise capacity has a mediating effect on the relationship between physical activity and autonomic function in patients with heart failure.

Purpose

To investigate the mediating effect of functional exercise capacity on the relationship between physical activity and autonomic function in patients with heart failure.

Methods

Patients with heart failure with reduced ejection fraction (HFrEF) were enrolled in this cross-sectional study. Autonomic function was evaluated with the heart rate variability analysis obtained from ECG recording. Physical activity was objectively assessed with an accelerometer. Functional exercise capacity was evaluated with the six-minute walk test (6MWT). The mediation model was tested with the SPSS Hayes process macro (model 4) (2).

Results

We included 61 patients with HFrEF (mean age 61.9 8.5; mean ejection fraction 31.26 6.62). The majority of patients were male (70.8%), overweight (45.8%) and NYHA functional class II (56.9%). The root mean square successive differences (RMSSD) index was significantly correlated with daily moderate to vigorous physical activity (MVPA) (r=0.528, p<0.001), and six-minute walk distance (6MWD) (r=0.594, p<0.001). The standard deviation of all normal RR intervals (SDNN) index was significantly correlated with daily MVPA (r=0.467, p<0.001), and 6MWD (r=0.490, p<0.001). The direct effect of MVPA on RMSSD was still statistically significant (B = 0.161 95% CI 0.006 to 0.316) after adding 6MWD. 6MWD partially mediated the effect of MVPA on RMSSD (indirect effect (B) = 0.159 95% CI 0.082 to 0.283), with the mediating effect accounting for 49.69% of the total effect. However, after adding 6MWD, the direct effect of MVPA on SDNN was removed (B = 0.171 95% CI -0.005 to 0.348), indicating that 6MWD completely mediated the relationship between MVPA and SDNN (indirect effect (B) = 0.125 95% CI 0.044 to 0.218).

Conclusion

Functional exercise capacity mediates the relationship between physical activity and autonomic function in patients with HFrEF. These findings indicate that improving functional exercise capacity through a structured exercise program, physical activity counselling, or both, may enhance autonomic function in patients with HFrEF. Figure 1. Correlations between variables.
Evaluating a dietetic educational intervention delivered to patients during hospital-based cardiac rehabilitation (CR)
Authors: Akl N , Cullen K C , Gallagher J G , Cahill A C , Hannon B H , Carroll L C , Dodd D D , Bryceland C B , Mulligan E M
Published: June 2024

Background/Introduction

Cardiac rehabilitation (CR) is an outpatient chronic disease management model recommended in clinical practice guidelines for patients with all forms of atherosclerotic cardiovascular diseases (ASCVD). Nutrition counselling is a core component of the prevention of non-communicable diseases including cardiovascular disease. While striving to deliver care in line with clinical practice guidelines, it is equally important to communicate nutritional information in an accessible way which accommodates varying degrees of health literacy. Therefore, effective delivery of dietetic educational intervention is an integral part of CR. Furthermore, measurement of treatment effectiveness and patient satisfaction are also recognized as important indicators of healthcare quality.

Purpose

To evaluate the effectiveness of the nutritional intervention in CR by (a) assessing improvements in patient’s baseline nutritional knowledge post-intervention; and (b) evaluating patients’ satisfaction with the dietetic intervention provided during CR.

Methods

The group educational intervention was informed by ESC (2021) guidelines and delivered in a discursive manner with patients encouraged to play an active role in the process. To evaluate the intervention a short battery of measures were administered to patients pre and post intervention over a 4-month period (April-August 2023). The study-specific questionnaire was based on the validated GNKQ (General Nutrition Knowledge Questionnaire) which was specifically adapted for the CR population.

Results

Participants were predominantly referred following Acute Coronary Syndrome (ACS), coronary artery disease (CAD) ± revascularization and valve disease (78% male, mean age 62 years). Thirty patients completed both the pre and post intervention evaluation measures (response rate 63%). Post intervention, 29 patients scored >60% on the nutritional knowledge measure (compared to 23 at baseline); 60% of patients were able to identify HDL as the good cholesterol (compared to 43% of patients not receiving the intervention). 77% of patients correctly answered the food labelling question after attending the dietetic session (compared to 63% of patients at baseline). 83% were also able to identify the recommended units of alcohol correctly compared to 47% of patients who did not receive the intervention. 18% of participants provided additional qualitative data which primarily indicated that patients viewed that their nutritional knowledge had improved but that further dietetic input was required.

Conclusion

Nutritional counselling is a core component of CR and the dietitian remains a vital member of the CR multi-disciplinary team. Although the dietetic intervention was successful in improving educational outcomes in some patients, resources should be directed to ensure patients receive optimal dietetic input and thus high-quality CR.
The effect of expiratory muscle strength training on oxidative stress and functional exercise capacity in patients with obstructive sleep apnea syndrome
Authors: Erturk N , Yaman H , Kahraman Yaman S , Celik A , Unal F , Calik Kutukcu E
Published: June 2024

Introduction

Obstructive sleep apnea syndrome (OSAS) is a respiratory sleep disorder with a risk of cardiovascular disease (CVD). Repeated episodes of hypoxemia and reoxygenation throughout the night lead to oxidative stress in OSAS. Expiratory muscle strength training (EMST) is a new effective intervention increasingly used in the rehabilitation of OSAS. In the literature, there is limited evidence about the effects of EMST in patients with OSAS.

Objective

We aimed to investigate the effect of EMST on CVD risk, oxidative stress and functional exercise capacity in patients with moderate OSAS who were refused or ineligible for other treatments.

Methods

Sixteen male patients (mean age: 44.12±6.13 years, mean BMI: 30.08±4.43 kg/m2) with moderate OSAS were included. CVD risk ratio calculated with SCORE2. The patients underwent a 12-week EMST program (60% of their maximal expiratory pressures, MEP) using a threshold loading device for 25 breaths per day, seven days per week. Respiratory muscle strength (inspiratory muscle strength-MIP and MEP) was measured. Total antioxidant level (TAS) and total oxidant level (TOS) were determined from serum blood samples. Oxidative stress index (OSI) was calculated. Functional exercise capacity was determined with a 6-minute walk test (6MWT).

Results

At baseline the patients SCORE 2 were min 1%-max 13%. After the 12-week EMST program, there was no significant difference in TAS values (p=0.205), while a significant decrease was observed in TOS (p<0.001) and OSI (p<0.001). MIP (p>0.001), MEP (p<0.001), 6MWT distance (p=0.001) significantly increased after training. No significant difference was observed in SCORE 2 ratios before and after treatment (p>0.05). There was a positive correlation between the ∆OSI and ∆6MWT distance values (r=0.603, p=0.013).

Conclusion

EMST decreases oxidative stress levels and increases respiratory muscle strength and functional exercise capacity in moderate OSAS patients. The rate of reduction in oxidative stress was associated with an increase in exercise capacity. EMST training is a promising treatment modality for OSAS.
Sport-related acute myocardial and tobacco smoking; findings from a regional prospective registry
Authors: Chague F , Kouame I , Braghini N , Bichat F , Maza M , Saint Jalmes M , Porot G , Molins G , Mock L , Ravisy J , Lhuillier I , Vincent-Martin M , Cottin Y , Zeller M
Published: June 2024

Background

Cigarette consumption is a major cardiovascular (CV) risk factor, especially when smoking just before or during exercise. Only few data are available on smoking in sport-related myocardial infarction (SR-MI).

Methods

We analysed characteristics of the smokers of IMACS, a regional prospective multicentre cohort including all patients hospitalised for a SR-MI. SR-MI was defined as MI onset occurring during sport or within the 1st hour of recovery. A one-year follow-up was performed by phone call.

Results

From April 1st 2018 to October 17th 2023, 151 SRMI were included, of whom 13 (8.6%) were female, median age was 61-y. and 39 (25.8%) were current smokers, of whom only 1 was woman (Table). Cycling was the most frequent sport (33.8%) followed by fitness (11.9%), jogging (11.3%) and hiking (10.6%). (Figure). When compared with non-smokers, smokers were 6.5 -y younger (P = 0.001). However, the rate of CV risk factor, STEMI, CV history and prodromal symptoms before the sport session were similar whatever smoking status. Among smokers, 26 (66.7%) declared cigarette consumption within the 2 hours before the sport session or the event. Out of hospital cardiac arrest (OHCA) occurred in 19 (12.6%) patients, more commonly among patients with prior coronary artery disease (CAD) (p = 0.04). OHCA was more common among smokers (p = 0.04); 8 of them (88.9%) had smoked within the 2 hours before the sport session or the event. At follow-up, only one patient suddenly died 8 days after discharge and another one benefitted from cardioversion delivered by its implanted automatic defibrillator (while doing do-it-yourself). Among the survivors at one year follow-up (131 patients, no patient lost in follow up), 97 benefitted from a rehabilitation program and 30 from the 34 smokers quitted. Among the quitters, 5 switched to electronic cigarette.

Conclusions

Although smoking is at high CV risk, especially in the setting of sport, the rate of smokers remains high (> 25%) in patients hospitalised for SR-MI. Moreover, almost two-third had smoked just before the event and appeared associated with occurrence of OCHA. These data highlight the need for prevention programs aiming to reduce the risk of tobacco, especially in sport setting.  Figure.
Cardiopulmonary exercise testing in patients with pulmonary arterial hypertension and the new four strata risk prediction model
Authors: Papageorgiou J M , Kylhammar D , Hedman K
Published: June 2024

Background

Cardiopulmonary exercise testing (CPET) is an established tool for follow-up of patients with pulmonary arterial hypertension (PAH). Recent PAH guidelines recommend a four-strata risk evaluation model at follow-up, not including CPET data. It is unknown how measures obtained at CPET relate to these new risk categories in patients with PAH.

Purpose

To explore standard CPET variables in patients with PAH in relation to the recently suggested four-strata risk assessment categories in PAH.

Methods

A single-center, retrospective analysis of patients diagnosed with PAH group 1 who underwent CPET between years 2007-2022. Patients were categorized as: low risk, intermediate-low risk, intermediate-high risk or high risk based on natriuretic peptide (NT-ProBNP), six minute walking distance (6MWD) and World Health Organization functional class (WHO-FC).

Results

In total, 23 patients (18 female, age 59 (41,69) years) with complete CPET and clinical data allowing accurate risk categorization were included. Thirteen patients were categorized as low-risk, six as intermediate-low and four as intermediate-high risk with no patient as high risk.

Figure 1 depicts CPET parameters comparing low-risk group, intermediate-low and intermediate-high risk group. Significant differences between the groups were found regarding peak oxygen uptake (VO2-peak) and the ventilation-to-carbon dioxide relationship (VE/VCO2-slope). More specifically, differences were significant between low-risk group vs intermediate-high risk group for VO2-peak (p-value 0.023) and VE/VCO2-slope (p-value 0.043).

Conclusion

We present that the new four-strata risk evaluation model in PAH is associated with marked differences in CPET parameters. This calls for further research evaluating the possible value of using CPET data in adjunct to the clinically based model.
Analyzing aortic stenosis-related mortality before and after transcatheter aortic valve replacement approval: insights from CDC data
Authors: Ashri S , Barbash I M , Fefer P , Segev A , Fishman B , Gerber Y , Maor E
Published: June 2024

Background

In recent decades, Transcatheter Aortic Valve Replacement (TAVR) has revolutionized the treatment landscape for aortic stenosis (AS). This study aimed to investigate the shifts in AS-related mortality rates before and after the introduction of TAVR in the United States (US).

Methods

Mortality data for all US adults (1999- 2020) were retrieved from the CDC WONDER dataset, encompassing all US death certificates and their associated causes. We analyzed AS-related age-adjusted mortality rates (AAMR) per 100,000 persons, contextualized with the FDA's TAVR approval for high-risk patients in 2012 and intermediate-risk patients in 2016. These rates were compared with mitral regurgitation (MR)-related mortality.

Results

We observed 306,376 AS- and 52,049 MR-related deaths. The average annual AAMR (95% CI) shifted from 4.21 (4.14, 4.28) in 1999-2012 to 4.31 (4.24, 4.38) in the years 2013-2016 and to 3.69 (3.63, 3.75) in the years 2017-2020 (FIGURE). Mitral valve AAMR also declined, however more moderately. While in pre-approval period, AS-related mortality was higher in rural compared with urban areas [4.42 (4.25, 4.59) and 4.16 (4.08, 4.24), respectively], the AAMR decline was comparable for both from the time of TAVR approval for high-risk patients to its approval for intermediate-risk patients, with a decrease of ~0.62 deaths per 100,000 persons annually for both demographics. Gender-specific analysis revealed that prior to approval, males exhibited higher mortality rates compared to females [4.59 (4.47, 4.72) vs. 3.94 (3.86, 4.03)]. However, the decline in mortality rates among males outpaced that among females (0.75 and 0.54 deaths per 100,000 persons annually, respectively.

Conclusions

Mortality rates associated with aortic stenosis have declined over the past two decades, with a clear temporal connection to the integration of TAVR into practice. Importantly, this decline was consistent across genders and geographical areas, suggesting that TAVR may play a pivotal role in mitigating health disparities within the US population.
Severe mitral regurgitation requiring surgery: comparison of repair versus replacement
Authors: Debski M , Qadri S , Bhalraam U , Debska K , Zacharias J , Vassiliou V
Published: June 2024

Background

According to ACC/AHA, ESC/EACTS and NICE UK Guidelines for the Management of Valvular Heart Diseases, when surgery is considered for primary mitral valve disease and mitral valve repair is expected to be durable according to the Heart Team evaluation, mitral valve repair is preferred over replacement as it is associated with better survival [1-3]. When repair is not feasible, experts advocate for mitral valve replacement with preservation of the subvalvular apparatus. These guideline recommendations are based solely on observational studies. In secondary mitral valve regurgitation, the advantage of mitral valve repair is less clear [4].

Purpose

This study aims to compare outcomes of repair and replacement in all aetiologies of severe mitral regurgitation in a tertiary cardiothoracic centre.

Methods

We compared the outcomes of 1751 consecutive patients (median age 69 [IQR, 60-75) who underwent first MV repair (n=1249, 71%) or replacement (n=503, 29%) for mitral regurgitation between 2000 and 2021. Patients undergoing aortic valve replacement and those with MV stenosis or mixed MV disease were excluded. Coronary bypass was performed in 36% of patients and 23% required tricuspid repair. Median follow-up was 7.1 (IQR, 3.6-11.6) years. To balance the cohorts, we used genetic matching with replacement which yielded 419 pairs of patients well-matched across 27 covariates (Figure 1) [5].

Results

Comparing the outcomes of mitral valve replacement to repair in the matched sample, we observed more frequent blood transfusion (29% vs 21%, p=0.013), longer intensive care unit (median 1 day [IQR, 1-2] vs 1 [IQR, 1-1], p=0.027) and post-operative length of stay (10 [7-15] vs 9 days [IQR, 7-12], p=0.002) . Regarding complications, we observed a similar rate of multiorgan failure, pulmonary and gastrointestinal complications. On the other hand, there were more strokes and transient ischaemic attacks in the mitral replacement group (6.7% vs 0.6%, p<0.001). In matched groups, MV replacement was associated with higher risk of mortality at 90-day (HR: 2.36, 95% CI: 1.31-4.25) and long-term follow-up (HR: 1.32, 95% CI 1.09-1.59) compared to MV repair (Figure 2). Repair was better in patients with degenerative mitral regurgitation, those <= 70 years old and elective cases. Patients > 70 years old, these with infective endocarditis, functional regurgitation and urgent cases had similar outcomes with either technique.

Conclusion

This study adds to the body of evidence supporting repair over replacement and broadens current understanding of early complications showing higher rate of cerebrovascular complications in MV replacement compared to repair. Balance before and after matching.  Kaplan-Meier survival curves.
General Comment No. 25 on Children’s Rights in Relation to the Digital Environment: Implications for Children’s Right to Privacy and Data Protection in Africa
Authors: Ayalew Yohannes Eneyew , Verdoodt Valerie , Lievens Eva
Published: June 2024

The UN Committee on the Rights of the Child has published its much-awaited General Comment No. 25 on children’s rights in the digital environment in 2021. Much of the conversations since its adoption have centred on how General Comment No. 25 influences State behaviours in the western world or globally. Little attention has been given as to what General Comment No. 25 means for children’s right to privacy in Africa. This article seeks to explore the role of General Comment No. 25 in clarifying States’ obligations in respect of children’s rights to privacy and data protection in the digital era on the African continent. In doing so, this article first contextualises General Comment No. 25 in the broader context of the United Nations human rights system and analyses its recommendations on children’s right to privacy. Second, the article examines children’s right to privacy in Africa and analyses the specific features of the African human rights system that influence the understanding of this right. Finally, the article illuminates certain child-specific privacy and data protection measures that are being or have been included or discussed in the law-making processes and policy debates in a selection of African countries and links them to both General Comment No. 25 and the socio-cultural context of the continent.
Risk factors associated with multidrug-resistant tuberculosis in areas with a moderate tuberculosis burden
Authors: Mansoori Noormohamad , Pahlavanzadeh Bagher , Atarjalali Masoumeh
Published: June 2024

Background

The emergence of multidrug-resistant tuberculosis (MDR-TB) or rifampicin-resistant (RR) TB poses a significant challenge for TB control initiatives on a global scale. This study’s aim was to estimate the incidence of MDR-/RR-TB and identify the risk factors associated with their incidence in four provinces in northern Iran.

Methods

Drug susceptibility testing was conducted using the proportion method on Lowenstein–Jensen media. The demographic and clinical data were collected from the Iranian TB registry.

Results

Among 1083 individuals diagnosed with TB, 27 (2.5%) were identified as having MDR-/RR-TB, while 73 cases (6.7%) were any drug resistant (ADR). The statistical analysis revealed a significant association between marital status and MDR-/RR-TB (p=0.003). In addition, significant associations were observed between ADR-TB and gender (p=0.035) and previous treatment for TB (p=0.02).

Conclusions

Our findings provide important information on the drug resistance pattern of Mycobacterium tuberculosis strains, as well as risk factors in northern Iran. Given the identified risk factors, creative approaches to promote treatment adherence in TB patients, particularly divorced/widowed women and individuals with a previous history of TB treatment, are required.
Population size and movement ecology of intertidal gastropods on rocky shores and seawalls in Singapore
Authors: Yeo Hannah H J , Loke Lynette H L , Todd Peter A
Published: June 2024

Increasing coastal development and global warming have resulted in large-scale habitat changes, with artificial coastal structures replacing extensive tracts of natural shores. In Singapore, for example, more than 63% of the natural coastline has been replaced by seawalls. Multiple studies from both temperate and tropical regions have compared species diversity supported by these artificial structures with natural rocky shores. Few, however, have estimated and compared the population size and movement of common intertidal species between these two habitat types. Using mark–recapture techniques, this study investigated: (1) the population size of three common gastropod genera (Nerita spp., Trochus spp. and Turbo spp.) and (2) differences in displacement of Nerita spp. and Trochus spp., two common species found on natural rocky shores and seawalls in Singapore. The results of our mark–recapture surveys indicated that seawalls supported large densities of Nerita spp.—more than 50 times greater than that on adjacent rocky shores. The mark–recapture data also revealed that movement of the gastropod species differed between the two habitats, with individuals on seawalls generally travelling longer distances.
Mucormycosis in Diabetes
Authors: Das Shukla , Rai Gargi , Gupta Chhavi , Gupta Neelima , Arora Vipin , Singh Praveen Kumar , Mohapatra Subhashree , Ansari Mohammad Ahmad , Hakami Zaki H. , Dar Sajad Ahmad
Published: June 2024

Fungal infections are a major health challenge especially in immunocompromised patients. Mucormycosis, a severe, frequently fatal fungal infection, has a unique predisposition to infect patients with diabetes. The infection is caused by organisms belonging to the order Mucorales, among which Rhizopus species are the most common. Uncontrolled diabetes complicated by diabetic ketoacidosis is one of the major risk factors for upsurge in mucormycosis cases. The defense mechanisms, involving macrophages and neutrophils for phagocytosis, are compromised in diabetes. In 2 cases of rhino-orbital-cerebral mucormycosis with underlying diabetes, we observed a marked immune imbalance, with elevated Th17 and diminished T regulatory cells. Recovery of CD4+CD25+ T cells after treatment indicated a favorable phenotype outcome; though high circulating CD4+CD161+ can be detrimental to the patient predisposing to future relapse(s). Mucorale specific T cells contributing to human immune responses against the fungi can be investigated to identify a surrogate diagnostic marker of invasive mucormycosis.
Characterization of zebrafish coagulation cofactors Fviii and Fv mutants and modeling hemophilia A and factor V deficiency
Authors: Dhinoja Sanchi , De Maria Anthony , Qaryoute Ayah Al , Jagadeeswaran Pudur
Published: June 2024

The aim of this study is to characterize zebrafish coagulation cofactors fviii and fv mutant fish and assess if they phenocopy classical hemophilia A and factor V deficiency in humans.

The embryos from fviii and fv zebrafish heterozygote mutants generated by ENU mutagenesis were purchased from the ZIRC repository. They were reared to adulthood and genotyped. The heterozygote male and female were crossed to get homozygote, heterozygote, and wild-type fish. Functional kinetic coagulation assays and bleeding assays were performed on normal and mutant adult fish, and venous laser injury assays were performed on the larvae.

The DNA from fviii and fv mutants were sequenced to confirm if they have a premature stop codon in exon 19, and in exon 2, respectively, and in both mutants, the amino acid glutamine is replaced with a stop codon. Homozygous and heterozygous 5 days post fertilization (dpf) larvae for fviii and fv deficient mutants exhibited prolonged time to occlusion after venous laser injury compared to wild-type controls. The homozygous and heterozygous fviii adult mutants showed modest bleeding and delayed fibrin formation in the kinetic partial thromboplastin time (kPTT) assay with their plasma. fv homozygous larvae had poor survival beyond 12 dpf. However, heterozygous fv mutants exhibited heavy bleeding and prolonged fibrin formation in the kPTT and kPT assay compared with wild-type siblings.

Our characterization showed fviii and fv mutants from ZIRC phenocopied to a considerable extent classical hemophilia A and factor V deficiency in humans, respectively. These models should be useful in studying and developing novel drugs that reverse the phenotype and in generating suppressor mutations to identify novel factors that compensate for these deficiencies.
Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis
Authors: Peng Jia-Ying , Wang Si-Yang , Chen Miao-Qi , Liu Cheng-Xin , Zhao Yi-Ting , Xu Tong-Shan , Wu Qian-Long
Published: June 2024

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = −0.72; 95% CI −0.88 to −0.56; P < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18–0.92; P < 0.05), exacerbations (OR = 0.10; 95% CI 0.05–0.18; P < 0.05), and recurrence (OR = 0.17; 95% CI 0.06–0.50; P < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP.

SYSTEMATIC REVIEW REGISTRATION

PROSPERO CRD42022362370.