bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of pacing-related differences on clinical and echocardiographic outcomes after TAVR with SAPIEN-3 valve
Authors: Lak H , Sammour Y , Chawla S , Gajulapalli R D , Kumar A , Parikh P , Svensson L G , Harb S , Tarakji K , Wazni O , Reed G W , Puri R , Krishnaswamy A , Kapadia S
Published: October 2021

Background

Data regarding the impact of pacing on outcomes after transcatheter aortic valve replacement (TAVR) is evolving especially with regards to pre-existing PPM. We examined the impact of new and prior PPM on clinical and hemodynamic outcomes after SAPIEN-3 (S3) TAVR.

Methods

Consecutive patients who underwent transfemoral-TAVR using S3 valve between April 2015 and December 2018 at our Clinic were included.

Results

Among 1028 patients, 10.2% required new PPM within 30 days, while 14% had pre-existing PPM. The presence of either prior or new PPM had no impact on 3-year mortality (log-rank p=0.6), or 1-year major adverse cardiac and cerebrovascular event (MACCE) (log-rank p=0.65). New PPM was associated with lower left ventricular ejection fraction (LVEF) at both 30 days (54.4±11.3% vs. 58.4±10.1%; p=0.001), and 1 year (54.2±12% vs. 59.1±9.9%; p=0.009) compared to no PPM. Similarly, prior PPM was associated with worse LVEF at 30 days (53.6±12.3%; p<0.001) and 1 year (55.5±12.1%; p=0.006) compared to no PPM. Interestingly, new PPM was associated with lower 1-year mean gradient (11.4±3.8 vs. 12.6±5.6 mmHg; p=0.04), and peak gradient (21.3±6.5 vs. 24.1±10.4 mmHg; p=0.01) despite no baseline differences. Prior PPM was also associated with lower 1-year mean gradient (10.3±4.4 mmHg; p=0.001), and peak gradient (19.4±8 mmHg; p<0.001), and higher doppler velocity index (0.51±0.12 vs. 0.47±0.13; p=0.039). Moreover, 1-year LV end-systolic volume (LVESVi) was higher with new (23.2±16.1 vs. 20±10.8 ml/m2; p=0.038), and prior PPM (24.5±19.7; p=0.038) compared to no PPM. Prior PPM was associated with higher moderate-to-severe tricuspid regurgitation (35.3% vs. 17.7%; p<0.001). There were no differences with regards to the rest of the studied echocardiographic outcomes at 1 year.

Conclusion

In this S3 cohort, new and prior PPM did not affect 3-year mortality or 1-year MACCE, however they were associated with worse LVEF, higher LVESVi and lower mean and peak gradients on follow-up compared to no PPM.

Funding Acknowledgement

Type of funding sources: None. Figure 1. All-cause Survival
Cerebrovascular accidents in patients supported with veno-arterial extra-corporeal membrane oxygenation- is duration of support important?
Authors: Hussain S , Zero N , Al-Saadi T , Asghar M , Glowacki N , Andrade A , Sciamanna C , Joshi A , Dia M , Macaluso G , Tatooles A , Pappas P , Cotts W , Pauwaa S
Published: October 2021

Purpose of study

Veno-Arterial Extra-corporeal Membrane Oxygenation (VA-ECMO) is indicated for refractory cardiac and/or respiratory failure. Adverse events remain considerable despite best practices. We specifically aimed to understand risk factors associated with cerebrovascular accidents (CVA) in patients who underwent VA-ECMO support.

Methods

We retrospectively assessed all VA-ECMO patients from 2007 to 2019 at our institution. We identified those who experienced a CVA while supported by VA-ECMO. Patients with the primary event (CVA) were matched to controls (no CVA) based on age and sex. Comparisons were made between groups using McNemar's, Mantel-Haenszel, and Wilcoxon Signed-Rank tests where appropriate.

Results

Of the 278 VA-ECMO patients in the registry, 32 patients who experienced a CVA were identified; 24 (8.6%) ischemic and 8 (2.9%) hemorrhagic. Median age was 59.5 years (inter-quartile range: 49–65 years) and 75% of patients were males. Hypertension, diabetes, CAD and CHF were common co-morbidities (Table 1). Cardiogenic shock was the most common indication for VA-ECMO support in both cohorts, 75% in cases and 71.9% in controls. Cannulation strategies were identified as central or peripheral. There was a significant association of duration of VA-ECMO support with incidence of CVA, with a p-value of 0.03. Regression analysis showed a trend of increased risk of CVA by 4% for each additional day on VA-ECMO, however, this was not statistically significant (Odds ratio: 1.04; confidence interval 1.00–1.08). Most common outcome was death followed by decannulation to recovery and bridge to LVAD.

Conclusion

Ischemic and hemorrhagic CVAs are not uncommon during VA-ECMO support. Our case control study shows an association of duration of VA-ECMO support with incidence of CVA. This underscores the importance of timely assessment and weaning or bridging of VA-ECMO patients to their next management step.

Funding Acknowledgement

Type of funding sources: None.
Protective effects of renal denervation based on MRI assessment of the brain in patients with resistant hypertension
Authors: Sukhareva A E , Falkovskaya A Y U , Baev A E , Ussov V Y U
Published: October 2021

Purpose

The purpose of this single-centre, prospective, comparative study was to evaluate the pattern and severity of the brain structural changes in patients with resistant hypertension based on MRI assessments and their changes one year after renal denervation.

Material and methods

The study comprised 58 patients with resistant hypertension (RH), aged 52.1±9.1 years, who underwent renal denervation (RDN) according to the good clinical practice guidelines. Patients underwent office blood pressure measurements, 24-hour blood pressure monitoring (BPM), and brain MRI scanning. Using brain MRI, the cerebrospinal fluid (CSF) system measurements, in particular the linear measurements of the cerebral lateral ventricles, the linear measurements of the external subarachnoid spaces in 6 regions (in the right and left frontal, parietal, and occipital lobes), sizes of the 3rd and 4th ventricles (length and width), dimensions of intracerebral cisterns (quadrigeminal, prepontine, and chiasmatic), the presence of periventricular leukoaraiosis and focal changes in the brain white matter were evaluated.

Results

Initially, patients with RH had a high incidence of the structural brain alterations: 75% with fine focal brain lesions, 75% with impaired CSF dynamics, 23% with sulcal widening, and 90% with periventricular oedema. After RDN, a significant hypotensive effect was noted. According to brain MRI, the number of patients without impaired CSF dynamics did not change significantly: 25% initially, and 20% a year later (χ2=0.63 p=0.43, and χ2=0.72 p=0.40). The number of patients with grade I impaired CSF dynamics after 6 months significantly increased after 12 months from 50% to 64% (χ2=4.00, p=0.046) due to lowering the number of patients without impaired CSF dynamics and patients with grade II impaired CSF dynamics (χ2=1.56, p=0.21). The number of patients with sulcal widening significantly decreased: from 23% to 8% one year following RDN (χ2=40.21 p=0.000). The incidence of periventricular cerebral oedema did not significantly change one year after the procedure; however, the incidence of fine focal brain lesions significantly decreased (from 75 to 60%, p=0.02).

Conclusion

Thus, it has been revealed that patients with RH are characterised by a high incidence of structural brain alterations based on MRI assessments. A year after bilateral renal denervation, there are significant improvement in intracranial hypertension signs and decrease in the incidence of fine focal brain lesions, without a significant change in the CSF dynamics parameters (Table 1). Figure 1 shows a clinical example of a decrease in the number of fine focal brain lesions after the intervention.

Funding Acknowledgement

Type of funding sources: None.
Association between isolated diastolic hypertension and cardiovascular events: a systematic review and meta-analysis of prospective cohorts
Authors: Huang M , Tang T , Cheng X
Published: October 2021

Background

Isolated diastolic hypertension (IDH) is a subtype of hypertension, which is defined as systolic blood pressure (SBP) <140 mmHg and diastolic blood pressure (DBP) ≥90 mmHg by 2018 European Society of Cardiology (ESC) guideline and 2019 National Institute for Health and Care Excellent (NICE). Whereas some previous studies have demonstrated the significant association between IDH and cardiovascular (CV) events, some have not.

Purpose

To assess the association between IDH and the risk of CV events, CV mortality, and all-cause mortality.

Methods

We conducted a systematic search for publications using Medline, Embase, and the Cochrane Library from inception through March 2021 for prospective cohort studies exploring the association between IDH and CV events, CV mortality, and all-cause mortality. Relative risks (RR) or hazard ratios were extracted from the selected studies. Random effect models with inverse variance weighting were used to calculate the pooled RR and 95% confidence interval (CI). The primary outcome was a composite of total CV events including CV mortality. The secondary outcomes were CV mortality and all-cause mortality. We defined the IDH as SBP <140 mmHg and DBP ≥90 mmHg, reference group as BP less than 140/90mmHg.

Results

Overall, 15 studies were identified including 1049587 participants (5.5% IDH). For the primary outcome, IDH was significantly associated with risk of CV events (RR, 1.40 [95% CI, 1.18–1.66], p<0.001). The increased risk of CV events was also observed in subgroup analyses based on age (less or more than 50) and sex. However, in further stratified analysis based on geographical region, only the Asia population showed a significant association with increased risk of CV events, whereas results were null in Europe and North America populations. For the secondary outcomes, IDH was significantly associated with increased CV mortality (RR [95% CI], 1.41 [1.12–1.78], p<0.001) but not with all-cause mortality (RR [95% CI], 1.13 [0.86–1.48], p=0.378). The sensitivity analysis showed the overall results did not vary significantly after exclusion of any one study.

Conclusions

IDH is associated with increased risk of CV events and CV mortality. Further, more large-scale prospective epidemiological cohorts are needed to confirm our conclusion.

Funding Acknowledgement

Type of funding sources: None. Primary outcomeSecondary outcomes
Cardiovascular multimorbidity and associated factors: the first Brazilian Registry of patients with hypertension
Authors: Batista S R , Vitorino P V O , Silva R R , Sousa A L L , Barroso W K S , Coca A
Published: October 2021

Background

Cardiometabolic multimorbidity (CM-MM) defined by the occurrence of at least two of morbidities (diabetes mellitus, stroke, acute myocardial infarction) is a important issue for health systems and it was associated with several health negative outcomes, especially decreasing of the life expectancy.

Purpose

To analyze the occurrence of CM-MM and associated factors among Brazilian patients with hypertension.

Methods

Cross-sectional study with participants of The First Brazilian Registry of Patients with Hypertension (BRH) from 45 sites in all regions of Brazil (n=2,646). For this study we select the individuals with ≥65 years (n=1,033) and CM-MM was defined with the presence of ≥2 of the following: diabetes mellitus, stroke, acute myocardial infarction evaluated by self related. CM-MM was analyzed according to sex, age, race, presence of others morbidities (dyslipidemia, myocardial revascularization, heart failure and chronic kidney disease), control of blood pressure, obesity, physical activity, actual smoking and alcohol consumption. The numerical variables were presented by median and interquartile range, the categorical variables by absolute and relative frequency. To verify the variables associated with the outcome, simple logistic regression was performed.

Results

CM-MM was present in 8.9% of participants. The median age was 71.6 (IQ: 67.9–76.8), female (59.7%), 65–70 years of age (39.6%), and 59.8% were white. Obesity was present in 55.8% and 48.4% of individuals have no blood pressure controlled. The occurrence of diabetes mellitus, stroke, and acute myocardial infarction was, respectively, 32.7%, 14.7% and 6.7%. A higher occurrence of CM-MM was observed in males, aged between 70 and 75 years old and with 75 years old or more, the presence of dyslipidemia; myocardial revascularization (MR); heart failure (HF) and kidney disease. The intersection size among diseases is represented in Figure 1. After multiple analysis, the following variables were associated with the presence of cardiovascular multimorbidity: male gender; age equal to or greater than 75 years and report of dyslipidemia, MR and HF.

Conclusions

The prevalence of CM-MM was high and an approach based on the clusters of cardiometabolic diseases can be a potent care strategy.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Intersection size among diseases CM-MM
A novel natural-derived pentameric peptide protects from angiotensin-evoked high blood pressure
Authors: Carrizzo A , Basilicata M G , Pepe G , Ciccarelli M , Di Pietro P , Campiglia P , Vecchione C
Published: October 2021

Background

Arterial hypertension is the most important risk factor for cardiovascular diseases, myocardial infarction, heart failure, renal failure and peripheral vascular disease. In the last decade, milk-derived bioactive peptides have attracted attention for their beneficial cardiovascular properties.

Methods

Here we combined in-vitro chemical assay such as LC-MS/MS analysis of buffalo ice cream, ex-vivo vascular studies evaluating endothelial and smooth muscle responses using pressure myograph, and translational assay testing in-vivo the vascular actions of PG1 administration in murine models.

Results

We demonstrate that a novel buffalo ice-cream-derived pentapeptide “QKEPM”, namely PG1, is a stable peptide that can be obtained at higher concentration after gastro-intestinal digestions (GID) of buffalo ice-cream (BIC). It owns potent vascular effect in counteract the effects of angiotensin II-evoked vasoconstriction and high blood pressure levels. Its effects are mediated by the inhibitory effect on AT1 receptor leading to a downregulation of p-ERK½/Rac1-GTP and consequent inactivation of NADPH oxidase activity.

Conclusions

These results strongly candidate PG1, as a novel bioactive peptide for the prevention and management of hypertension, thus expanding the armamentarium of preventive strategies aimed at reducing the incidence and progression of hypertension and its related cardiovascular complications.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): University
Association of residential distance to coast with myocardial infarction: a prospective cohort study
Authors: Zhuang Z X D , Liao X X , Zhang S Z
Published: October 2021

Background

Little is known about whether the residential distance to coast is associated with incident myocardial infarction (MI), as well as which mechanisms may explain the association. We aim to explore this association using data from a prospective, population-based cohort with unprecedented sample size and broad geographical coverage.

Methods

377,340 participants from the prospective, population-based UK Biobank cohort were included. Residential distance to the coast was defined as participant's residence location to coast.

Results

4,059 MI occurred during median 8.0 years follow-up. Using group (<1 km) as reference, group (20–50 km) was associated with lower risk of MI (hazard ratio, HR 0.79, 95% CI 0.64–0.98) and a U-shaped relation between distance to coast and MI was shown with the low risk interval between 32 km and 64 km (Pnonlinear = 0.0012). Using participants of intermediate region (32–64 km) as reference, participants of offshore region (<32 km) and inland region (>64 km) were both associated with a higher risk of incident MI (HR 1.12, 95% CI 1.04–1.21 and HR 1.09, 95% CI 1.01–1.18, respectively). HR for offshore region (<32 km) was larger in subgroup with low total physical activity (<24 hours/week) (HR 1.24, 95% CI 1.09–1.42, Pinteraction = 0.043), whereas HR for inland region (>64 km) was larger in subgroup in urban area (HR 1.12, 95% CI 1.03–1.22, Pinteraction = 0.065) and in subgroup of high nitrogen dioxide air pollution (HR 1.29, 95% CI 1.11–1.50, Pinteraction = 0.021).

Conclusions

Our findings highlight the complex and diverse associations between residential distance to the coast and incident MI.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Impact of the first coronavirus-disease pandemic wave on cardiovascular admissions and sudden cardiac death rates in Greece
Authors: Pagourelias E , Vassilikos V P , Katsos K , Zaggelidou E , Raikos N , Tzikas S , Tsavousoglou C , Kouparanis A , Anastasakis A , Kassimis G , Ziakas A , Sianos G , Karvounis H , Kanonidis I , Spiliopoulou C
Published: October 2021

Background

Various studies suggest a decrease of hospital admissions for acute coronary syndromes (ACS) during COVID-19 outbreak, implying an increase in ACS related pre-hospital-care deaths as a cause of this phenomenon.

Purpose

Aim of this study was to investigate the impact of social containment measures on ACS admission and acute coronary deaths (ACDs) rates in Greece, during COVID-19 first pandemic wave in 2020.

Methods

Data for this analysis were retrieved by the official records of University Forensic and Cardiology Departments and the Forensic Science Services of the most crowded metropolitan areas of Greece (almost 25% of the entire Greek population ≈ 2.5 million people). The study period was defined as the time between March 15 2020, when the Greek state started to implement strict lock-down measures to contain COVID-19 pandemics, until April 14 2020. To compare admission and SCD rates, a corresponding control period a year earlier was chosen. Incidence rates (IRs) (events over days) of ACSs and ACDs in each time-period were assessed along with IRs ratios (IRRs) and 95% CI intervals. Secondary analysis for non-ischemic cardiovascular deaths (CVDs) or violent deaths (VDs) (including road traffic accident deaths) was also performed.

Results

There has been a relative 38.9% reduction in ACS admissions in 2020 [1.8, 95% CI (1.35–2.34) in 2019 vs 1.1, 95% CI (0.76–1.54) in 2020, p=0.02], concordant with a 66% relative reduction of total admissions (p<0.005). Overall, 171 deaths in 2020 vs 208 in 2019 were referred for autopsies in the enrolled forensic departments. Gender and age distribution were not significantly different between case and control periods. There were no statistically significant differences in the frequency of deaths between the two periods examined, with the exception of deaths secondary to road traffic accidents [IR 0.13, 95% CI (0.04–0.34) in 2020 vs 0.67, 95% CI (0.41–1.03) in 2019, p=0.001] and CVDs [IR 0.43, 95% CI (0.23–0.74) in 2020 vs 1.03, 95% CI (0.70–1.47) in 2019, p=0.007] which significantly decreased during COVID-19 pandemic wave. Absolute numbers, percentile changes and IRs are demonstrated in Figure 1 and Table 1.

Conclusions

Our analysis offers evidence over a significant decrease in ACS-related hospitalization rates during COVID-19 first pandemic wave. This decrease is not linked to an increase in pre-hospital, autopsy defined ACDs, as previously thought, implying that many ACS patients may not ask for help on time due to infection fear, being prone however to late-onset complications. Pre-hospital triage and care services, should be appropriately transformed to facilitate and speed-up access of cardiovascular patients to health-care systems during the pandemic.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Emotional and cardiovascular health: the impact of depression on cardiac autonomic activity
Authors: Theofilis P , Oikonomou E , Lazaros G , Vogiatzi G , Tsalamandris S , Chasikidis C , Fountoulakis P , Anastasiou M , Goliopoulou A , Mystakidi V X , Papakonstantinou M , Christoforatou E , Siasos G , Tousoulis D
Published: October 2021

Background

The coexistence of depression and cardiovascular diseases is frequently accompanied by an increased risk of adverse outcomes. QTc, an indicator of ventricular depolarization and cardiac autonomic activity, has been proposed as a biomarker of this interplay.

Purpose

We aimed to investigate the possible association of depression with QTc interval.

Methods

Assessment of depressive symptoms was performed in 1637 participants of the cross-sectional Corinthia study with the Zung self-rating depression scale in those younger than 65 years of age (Group 1) and with the geriatric depression scale in elderly individuals (>65 years, Group 2). Moreover, electrocardiogram was performed and measurement of the QT interval was derived after correction for heart rate (QTc) using the Bazett's formula. Abnormal QTc was present when QTc duration exceeded 440 ms.

Results

Group 1 individuals classified as having depression had longer QTc duration (No depression: 389.3±27.0 ms vs. Depression: 401.1±32.9 ms, p<0.001) and percentage of abnormal QTc (No depression: 2.0% vs. Depression: 10.8%, p=0.001) (Figure 1, Panels A and B). Elderly individuals had similar values of QTc (No depression: 409.9±29.6 ms vs. Depression: 405.2±46.4 ms, p=0.37) and percentage of abnormal QTc (No depression: 13.2% vs. Depression: 12.3%, p=0.78) irrespective of depression status (Figure 1, Panels C and D). The presence of depression in Group 1 subjects was associated with an increased QTc- by 10.8 ms and with an approximately 7-fold higher prevalence of abnormal QTc duration, even after adjustment for confounders (). Such finding was not detected in elderly individuals (Figure 1, Panel F).

Conclusion

Depression might adversely affect ventricular repolarization especially in middle-aged subjects. These findings highlight the interrelationship between emotional and cardiovascular health and the role of depression as a cardiovascular risk factor.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Cardiovascular risk profile in Portugal: evidence from a large population-based cohort
Authors: Gavina C , Araujo F , Pardal M , Grangeia D , Moreira F , Leitao A , Taveira-Gomes T
Published: October 2021

Background

The rising prevalence of CVD in Portugal translates into more than 35 thousand annual deaths (1,2), with stroke and ischemic heart disease as the leading causes of death (3). Reducing the incidence of ASCVD is a public health priority, for which LDL-C lowering is paramount to halt atherosclerotic plaque progression (4,5). Real-world data is lacking regarding patient characterization, lipid-lowering therapy, and LDL-C levels by CV risk profile.

Purpose

To assess the proportion of patients with low, intermediate, high, and very high CV risk in a population with a complete spectrum of care, and describe their clinical characteristics, cardiovascular medications, and degree of LDL-C control.

Methods

This non-interventional, cross-sectional study included adult patients between 40 and 80 years old followed for primary or secondary CV risk prevention at a major healthcare institution that provides both primary and hospital care. Patient data spanned the period from 1/1/2008 to 31/12/2019. The index date for patient identification and characterization was 31/12/2019. CVD risk assessment was computed according to the 2019 ESC/EAS Guidelines for the management of dyslipidemias (6). Every criterion for risk assessment (excluding imaging and family history) was reconstructed using the most granular available records of clinical observations, measurements, episodes, lab orders, diagnosis and medications recorded at all primary and secondary care sites of the institution. We described patient demographic and clinical characteristics for each CV risk level, lipid-lowering treatment (LLT), and LDL-C levels.

Results

We identified 111.394 patients eligible for analysis. Sufficient records for CV risk assessment were available for 82.271 patients. According to 2019 ESC/EAS Guidelines CV risk categories, 25.7%, 21.4%, 12.2% and 40.7% of patients had low, intermediate, high and very high CV risk. High/very high CV risk patients had a mean (SD) age of 65.6 (10.1) years. Type 2 diabetes was present in 13.1% of high CV risk and 40% of very high CV risk groups. Although approximately 70% of patients with high/very high CV risk were treated with a LLT, only 5.1% of high CV risk and 3.6% of very high CV risk had LDL-C levels within the recommended targets. There was a very low use of high intensity statins or combination therapies in high/very high CV risk categories (table 1). Patients with atherosclerotic CV disease accounted for 34.6% of those at very high CV risk and only 4.8% attained desired goals (table 2).

Conclusions

There is a pressing need for better control of LDL-C levels at every stage of CV risk, with a particular focus on high and very high CV risk patients. Effective strategies for LCL-C control are thus needed.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This study was funded by Novartis Farma, Produtos Farmacêuticos S.A.
Prediction of future atherosclerosis in 13 years from young asymptomatic adults
Authors: Huynh Q , Magnussen C , Venn A , Dwyer T , Marwick T
Published: October 2021

Aim

To compare the Pooled Cohort Equation (PCE) and Ideal Cardiovascular Health Score (ICHS) with a simpler cardiovascular risk score not requiring laboratory tests (the Fuster-BEWAT score, FBS) in predicting the presence and extent of subclinical atherosclerosis 13 years later.

Methods

Data included 894 adults (48% male) who were aged 26–36 years at baseline and 40–50 years at follow-up. The primary outcome was the presence of carotid plaque measured by ultrasound at follow-up. Secondary outcomes were number of arteries affected, plaque thickness and plaque area. All three scores were calculated at both baseline and follow-up.

Results

At follow-up, 86 participants (9.6%) had unilateral carotid plaques and 23 participants (2.6%) had bilateral carotid plaques. At baseline, all three scores were predictive of the presence of carotid plaque at follow-up (PCE odds ratio (OR) = 1.42 [95% CI: 1.19–1.70], ICHS OR=0.87 [0.77–0.99], FBS OR=0.86 [95% CI: 0.77–0.96]) and all secondary outcomes. All baseline scores predicted outcomes more strongly than those at follow-up, and did so independent of any changes over 13 years of follow-up. Similar levels of discriminatory power were found for all three baseline scores in predicting the presence of carotid plaque after 13 years (PCE C-statistic = 0.69 [95% CI: 0.63–0.75], ICHS C-statistic = 0.67 [95% CI: 0.61–0.74] and FBS C-statistic = 0.68 [95% CI: 0.62–0.74])

Conclusions

All baseline scores predicted subclinical atherosclerosis 13 years later. The similar discrimination of the scores highlights the benefit of using FBS as a simpler and more feasible risk score for predicting future cardiovascular risk in low-risk young people.

Funding Acknowledgement

Type of funding sources: None.
Association of physical signs with genotype, lipid- and inflammation-related markers, coronary stenosis or calcification, and outcomes in patients with heterozygous familial hypercholesterolemia
Authors: Liu M M , Li J J
Published: October 2021

Background

Although several previous studies indicated that the existence of physical signs [tendon xanthomas or corneal arcus (TX/CA)] was associated with the risk of coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolemia (HeFH), its relations to genotypes and clinical characteristics have not been fully determined. The present study aims to examine the association of TX/CA with genetic mutation, lipid and inflammation-related markers, coronary calcification, coronary severity and cardiovascular events (CVE) in Chinese patients with HeFH.

Methods

A total of 489 HeFH patients diagnosed with Dutch Lipid Clinic Network (DLCN) criteria and/or genetic testing were consecutively recruited. To compare the patients with TX/CA versus those without, propensity score matching (1:4 matched) was performed to adjust for age and sex. Patients were finally divided into the TX/CA group (n=50) and non-TA/CA group (n=200). Data including genetic mutation [low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9)] and laboratory analysis including lipoprotein(a), PCSK9, high-sensitivity C-reactive protein (hsCRP), computed tomography angiography, coronary angiography, and follow up CVEs were compared.

Results

Patients with physical signs presented significantly higher LDL cholesterol levels (8.65±2.53 vs. 7.70±2.18 mmol/L, p=0.025), more LDLR (+) mutations (OR 2.896, 95% CI 1.295–6.473, p=0.010), higher prevalence of high tertiles of Gensini, SYNTAX and Jeopardy score, and coronary artery calcium scores compared to those without. In addition, patients in the TX/CA group had a higher prevalence of high PCSK9 and hsCRP tertiles compared with those without signs. Over an average of 3.7 years of follow-up, patients with TX/CA were at a significantly greater risk of CVE (multivariate adjusted hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.14–6.90, p=0.024).

Conclusions

The physical signs were associated with positive genetic mutation, higher PCSK9 or hsCRP concentration and worse outcomes in patients with HeFH, suggesting that these signs may help to risk stratification in patients with HeFH.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Capital Health Development Fund (201614035) and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2016-I2M-1-011)
Sex modifies the association between body mass index and carotid artery intima media thickness in the multi-ethnic Singapore population
Authors: Dalan R , Mina T , Nur Azizah N A , Tong T , Loh M , Wansaicheong G , Chambers J
Published: October 2021

Background and aims

Globally cardiovascular disease (CVD) risk is higher in men than in women in the younger age group but the risk is attenuated in later life with an unexpected higher risk in women in some populations. A better understanding of sex differences in CVD is needed. Carotid artery intima-media thickness (CIMT) has been proposed for CVD risk assessment in individuals at intermediate risk. We study the gender interactions in the associations of the traditional cardiovascular risk factors with CIMT.

Methods

We performed carotid ultrasonography in the large population health study-HELIOS conducted in Singapore. Measurements were performed as per Mannheim consensus, at the far wall of bilateral common carotid artery at 8 sites in each participant. We report the average of all measurements (avgCIMT) and maximum value (maxCIMT). We analysed 2061 healthy participants recruited between 2018–2020. Inclusion criteria for this analysis: non-smokers, not known to have diabetes, hypertension, hyperlipidemia or ischemic heart disease. Individuals with systolic blood pressure >160 mm Hg or fasting glucose >7.0 mmol/L on recruitment were excluded. Multivariable linear regression analysis was performed to examine the association between CIMT and cardiovascular risk factors in the healthy population adjusting for age, sex and ethnicity. All analysis was performed using Stata version 16.0.

Results

After exclusion, 1407 healthy participants were included in the analysis. Median (IQR) avgCIMT: 0.56 (0.50, 0.65) in men; 0.54 (0.50, 0.58) in women. Median (IQR) maxCIMT: 0.64 (0.57, 0.76) in men; 0.61 (0.54, 0.70) in women. The avgCIMT and the maxCIMT were higher in males when compared to women and all traditional cardiovascular risk factors associated with CIMT after adjustment for age, sex and ethnicity (P<0.05) (Table 1). Interaction tests in multivariable model adjusted for age, ethnicity, pulse pressure, non HDL-C and HbA1c showed a significant interaction between sex and body mass index (BMI) with predicted effects on avgCIMT and maxCIMT being relatively higher in males at the same BMI when compared to females (P-interaction <0.01) (Figure 1).

Conclusion

Sex modifies the relationship between BMI and CIMT in Singapore's multi-ethnic population. Understanding the intermediary mechanisms involved will help in developing personalized preventive strategies.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Effect of statin on progression of degenerative aortic root dilatation
Authors: Avinashsingh Eswarsingh A S , Bose A B , Islam T S , Shah S H , Alampoondi Venkataramanan S A I , Muthyala A M , Manohar S M , Rupendu S R , Shah N S
Published: October 2021

Background

Aortic root dilatation (ARD) is the most common thoracic aortic aneurysm (TAA). Causes of TAA include congenital and heritable disorders, degenerative disorders, inflammatory and infectious etiologies (1.) Hypertension management and smoking cessation are the two most important risk factor modification strategies to prevent rapid progression (>2 mm/year) of TAAs. Beta blockers and angiotensin receptor blockers are the preferred agents to treat HTN (5,6). Statin use is associated with a lower rate of progression of ascending arch and thoracoabdominal aortic aneurysms (2,3,4). However, their role in the progression of degenerative ARD remains unclear.

Purpose

To evaluate the association between statin use and progression of ARD.

Methods

A retrospective chart analysis was performed on 340 patients with a known diagnosis of degenerative ARD. Aortic root measurements were followed by serial transthoracic echocardiograms from the time of first diagnosis for a total of 10 years. The study population was dichotomized based on statin use. The mean change in ARD was calculated for each patient in millimeters. Baseline characteristics were compared between the groups. Multivariate adjusted linear regression models were used to estimate unit change in mean ARD change based on statin use.

Results

Patients in the statin group were older, more obese, with a higher prevalence of comorbidities and medication use compared to patients not on statin. Over a 10-year follow up, the mean increase in ARD was comparable for statin vs. non-statin users (0.83 mm vs. 0.73 mm, p=0.53). On a multivariate regression model adjusted for baseline demographics, risk factors and medication use, the statin group showed a 0.16 mm reduction in ARD compared to non-statin group but this decrease was not statistically significant (Table 1, p=0.47)

Conclusion

In patients with degenerative ARD on a pre-existing regimen of statin, there was no statistically significant change in ARD.

Funding Acknowledgement

Type of funding sources: None. Table 1
Neurological outcome at 30-day as an estimator of 1-year functional status after out-of-hospital cardiac arrest with post-encephalopathy
Authors: Nitta G , Matsuda J , Kato S , Hada Y , Inaba O , Matsumura Y , Nozato T , Ashikaga T , Sasano T
Published: October 2021

Background

Implantation of implantable cardioverter-defibrillators (ICD) for secondary prevention is fully recommended for those with an estimated survival over 1-year with a good functional status. However, we often face the difficulty to estimate the functional status and hesitate to implant ICD for patients with post-resuscitation encephalopathy.

Methods

There were 2391 out-of-hospital cardiac arrest (OHCA) patients transferred to 2 hospitals. We included 405 cardiovascular arrest patients, who got return of spontaneous circulation (ROSC) from January 2015 to December 2018. Among the patients, 343 patients could be considered to be implanted ICD for secondary prevention according to the initial waveform or the causes of OHCA. At 1-month later, 184 patients (54%) survived. To assess the association of functional status at 30-day and 1-year, we investigated patients' characteristics, pre-hospital information and clinical findings, and evaluated the neurological outcome according to the cerebral performance category (CPC) scale.

Results

At 1-month later, 145 patients (79%) survived with CPC≤2, and 39 patients (21%) survived with CPC>2. Bystander CPR (P=0.009), pre-hospital ROSC (P<0.001), low lactate level on admission (P=0.001), high geriatric nutritional risk index score (P<0.001) and without ECMO (P=0.002) were significantly associated with good neurological outcome at 30-day. The 1-year Kaplan-Meier event rate revealed significantly different survival rate (CPC>2 at 30-day:38.5%, vs CPC≤2 at 30-day:97.2%; P<0.001). In multivariate analysis, CPC scale at 30-day (OR 0.022; 95% CI 0.003–0.140; p<0.001) was the independent predictor of favorable neurological outcome at 1-year. Among the patients with CPC>2 at 30-day, only 3 patients (7.7%) of CPC=3 achieved the improvement of neurological outcome at 1-year (CPC≤2), while no patient of CPC=4 did. And one patient (2.5%) with CPC=3 was implanted ICD during the follow-up period. Twenty-five patients (64%) died of non-cardiovascular death with frailty of post-resuscitation encephalopathy after they were transferred to other hospital with the acceptation and intention of the do-not-attempt-resuscitation.

Conclusions

Neurological prognosis at 30-day after OHCA might be an estimator of 1-year functional status to guide us to implant ICD for secondary prevention.

Funding Acknowledgement

Type of funding sources: None.
Atherosclerotic cardiovascular risk and simulation of lipid-lowering therapy in China
Authors: Bi L E I , Yi J Y , Wu C Q , Lu J P , Zhang H B , Yang Y A N G , Li X I , Zheng X I N
Published: October 2021

Background

Lipid-lowering therapy is a key strategy to reduce atherosclerotic cardiovascular disease (ASCVD) risk. However, little is known about the burden of lipid-lowering therapy in China.

Purpose

We aim to simulate the proportion of individuals in need of different lipid-lowering therapy regimens to reach diverse low-density lipoprotein cholesterol (LDL-C) goals based on the ASCVD risk stratification.

Methods

We used the data from China PEACE Million Persons Project, a national screening project covering 31 provinces in China. The ASCVD risk stratifications and LDL-C goals were based on the 2016 Chinese Guideline for the Management of Dyslipidemia in Adults. Stepwise lipid-lowering therapy (atorvastatin 20 mg, add-on ezetimibe and add-on evolocumab) was simulated by a Monte Carlo model based on individual's LDL-C level.

Results

We included 2,876,272 participants (89.7% of the screened) who were not receiving lipid-lowering therapy (mean age 55.8±9.9 years; 60.5% women). The proportion of participants at low, moderate, high and very high ASCVD risk were 57.9%, 17.5%, 22.3% and 2.3%, respectively. In individuals at low or moderate risk, 10.5% did not reach the goal of LDL-C<3.4mmol/L; after statin simulation, 99.8% met the goal. In high-risk patients, 49.0% did not reach LDL-C<2.6mmol/L; after statin monotherapy (82.7%), add-on ezetimibe (10.6%) and add-on evolocumab (6.7%), 99.7% met the goal. In very-high-risk patients, 72.2% did not reach LDL-C<1.8mmol/L; while 99.1% met the goal after all patients received the simulation: statin monotherapy (76.5%), add-on ezetimibe (13.0%) and add-on evolocumab (10.5%). In a total of 609,489 participants (21.2% of the overall participants) needing lipid-lowering therapy, 88.5% required statin monotherapy and 11.5% additional non-statin therapy (Figure).

Conclusions

Moderate-intensity statin therapy is pivotal in the lipid-lowering therapy in China; nearly 10% in need of lipid-lowering therapy required additional non-statin therapy.

Funding Acknowledgement

Type of funding sources: None.
Very low high-density lipoprotein-cholesterol and long-term mortality
Authors: Dykun I , Hendricks S , Babinets O , Al-Rashid F , Totzeck M , Rassaf T , Mahabadi A A
Published: October 2021

Background

High-density lipoprotein-cholesterol (HDL-C) has anti-atherogenic, anti-inflammatory, anti-oxidative, anti-apoptotic, and vasodilatory properties. While a linear inverse relationship between HDL-C levels and all-cause mortality is established, recent observational studies suggest a U-shaped association between HDL-C and outcome.

Purpose

We tested the hypothesis that both low and high HDL-C levels associate with long-term mortality.

Methods

The present analysis is based on the longitudinal ECAD registry of consecutive patients undergoing coronary angiography at the West German Heart and Vascular Center between 2004 and 2019. HDL-C was quantified at hospital admission using standardized enzymatic methods. The incidence of death due to any cause was evaluated during follow-up. Cox regression analysis was used to determine the association of HDL-C with incident mortality, adjusting for age, sex, systolic blood pressure, low-density lipoprotein cholesterol, smoking status, and family history of premature cardiovascular disease. In addition to the analysis on HDL-C as continuous variable, the association of HDL-groups (<10th percentile, 10th-<25th percentile, 25th-<50th percentile, 50th-<75th percentile, 75th-90th percentile, and ≥90thpercentile) with incident mortality was determined using HDL-C <10th percentile as reference.

Results

Among 17,433 patients, mean age was 65.9±12.6 years and 70.1% were men. Mean HDL-C was 48.7±16.2 mg/dL. During a mean follow-up 3.38±2.10 years, 2,401 patients (13.8%) died. In multivariable analysis, higher HDL-C levels were independently associated with lower all-cause mortality [hazard ratio (95% confidence interval): 0.83 (0.76, 0.91) per 1 standard deviation change in HDL-C, p<0.001]. Associations between HDL-C and mortality were equally present in male [0.83 (0,74, 0.93), p=0.001] and female patients [0.85 (0.73, 1.00), p=0.0496]. Using HDL-C <10thpercentile as reference (<31mg/dl), all other HDL-C groups showed stable effect sizes below 1.0 without signs of increasing morality probability in high HDL-C groups [0.50 (0.44, 0.58), p<0.001; 0.41 (0.36, 0.46), p<0.001; 0.37 (0.32, 0.42), p<0.001; 0.36 (0.36, 0.31), p<0.001; and 0.40 (0.34, 0.47), p<0.001 for HDL-C 31–37 mg/dL, 38–45 mg/dL, 46–56 mg/dL, 57–69 mg/dL, and ≥70mg/dl, respectively].

Conclusions

In a large longitudinal registry cohort of patients undergoing invasive coronary angiography, only very low HDL-C levels were associated with increased long-term mortality. We found no signs of a U-shaped association between HDL-C and prognosis.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Iryna Dykun was supported by the German Research Foundation (DY 149/2-1)Stefanie Hendricks was supported by the Universitätsmedizin Essen Clinician Scientist Academy (UMEA)
Statin-associated muscle symptoms in clinical practice: evidence from a 6-year retrospective study
Authors: Barkas F , Adamidis P , Koutsogianni A D , Anastasiou G , Liamis G , Elisaf M , Liberopoulos E
Published: October 2021

Introduction

There is conflicting evidence regarding the prevalence of statin-associated muscle symptoms (SAMS) in clinical practice and randomized clinical trials.

Aims

We aimed to record SAMS prevalence in the setting of a specialized lipid clinic.

Methods

This was a retrospective study including adults with dyslipidemia who were followed-up for ≥3 years (1999–2015) at the outpatient Lipid Clinic of our University General Hospital, Greece. We evaluated subjects' clinical and laboratory data with an emphasis on the prevalence of SAMS (including myalgias, muscle crumps and creatine kinase, CK, increase >10 upper limit of normal values) and recorded the rates of low-density lipoprotein cholesterol (LDL-C) target attainment according to the current ESC/EAS guidelines.

Results

Among 1,334 dyslipidemic subjects followed-up for 6 years (4–10), the prevalence of SAMS was 3% (n=41); 2% reported myalgias/crumples and 1% exhibited increased CK levels once. Only 7% (n=3) of those were statin intolerant, whereas the rest were able to receive any maximally tolerated statin dose. The corresponding prescription rates for low-, moderate- and high-intensity statins were 12%, 61% and 20%, respectively, whereas 32% received combination treatment with ezetimibe. None of the statin intolerant patients and 12% of those treated with any tolerated statin dose had optimal LDL-C levels.

Conclusions

The prevalence of SAMS is low in the setting of a specialized lipid clinic. Therefore, physicians should cautiously work-up to identify individuals with clinically relevant SAMS to offer alternative therapeutic regimens satisfactorily addressing their cardiovascular risk.

Funding Acknowledgement

Type of funding sources: None.
The relationship between visceral fat depots and markers of renal dysfunction in patients with borderline arterial hypertension and obesity
Authors: Erbes P E , Shulkina S G , Byvaltseva E N , Antipova A A , Smirnova E N , Kolomeets N Y
Published: October 2021

Introduction

Obesity is a potent risk factor for the development of kidney disease (CKD). The localization of adipose tissue and its hormonal activity plays an important role in the formation of the cardiorenal relationship.

Purpose of work

To assess the relationship between visceral fat stores with hormonal activity of adipose tissue, metabolic parameters and markers of renal dysfunction in patients with borderline arterial hypertension (AH) and obesity.

Materials and methods

The study included 100 people aged 44.8±6.4 years. Group 1 – patients with borderline hypertension – SBP 134.1±4.7 mm Hg; DBP – 84.3±5.9 mm Hg, BMI 36.1±3.2kg/m2. Group 2 was patients with BMI 35.5±3.9 kg/m2, SBP level 120.6±10.1 mm Hg and DBP 70.1±8.4 mm Hg. Albumin/creatinine ratio urine (ACRU), β2 microglobulin, tumor necrosis factor (TNF), interleukin 6 (IL6), monocytechemoattractant protein (MCP-1) was determined in a single portion of morning urine, the level of leptin, resistin and cystatin C was determined by ELISA. Glomerular filtration rate (GFR) was calculated using the CKD-EPI formula and cystatin C (Hoek's formula). The examination of visceral adipose tissue (VAT) was using an ultrasound method of investigation: the epi- and pericardial fat depots were assessed; VAT 1 – measurement at the level of the navel from the inner surface of the rectus abdominis to the posterior wall of the aorta and L4; VAT 2 – measurement at the level of the navel from the inner surface of the rectus abdominis to L4; the thickness of the posterior perirenal VAT on the right and left and the area of perirenal fat on both sides.

Result

The amount of fat depots in the groups is shown in Table 1. Indicators of hormonal activity of adipose tissue and renal markers are presented in Table 2. In the group with borderline hypertension the relationship between VAT 1 and 2 with ALT levels (r=0.40) and (r=0.42) was established, AST (r=0.52) and (r=0.47); HDL (r=−0.67) and (r=−0.70), TG (r=0.38) and (r=0, 39), HOMA index (r=0.45) and (r=0.39), MCP-1 (r=0.28) and (r=0.36). Perineal fat depot located to the right and left is correlated with LDL (r=0.40) and (r=0.37), glucose (r=0.49) and (r=0.50), ACRU (r=0.43) and (r=0.57), urinary excretion of cystatin C (r=0.28) and (r=0, 39). The connection with the optimal blood pressure level in control group was established between the perineal adipose tissue on the right and the left with the level of TG (r=0.35) and (r=0.29), GFR according to Hoek (r=0.29) and (r=0, 38), MCP-1 (r=0.36) and (r=0.29).

Findings

The increase of perinephral adipose tissue in obese patients is associated with an increase in cytokine excretion in the urine, an increase in VAT is accompanied by a deterioration in metabolic parameters.

Funding Acknowledgement

Type of funding sources: None.