bluuebunny/crossref_metadata_2025 huggingface dataset:
Type 1 and 2 matrix metalloproteinases, tissue inhibitor of metalloproteinases and left ventricular diastolic dysfunction in hypertensive patients
Authors: Lareva N , Kalinkina T , Govorin A
Published: October 2021

The purpose of the study. To assess the level of matrix metalloproteinases of types 1 and 2 (MMP1, MMP2), as well as tissue inhibitor of metalloproteinases (TIMP) in relation to indicators of left ventricular myocardial deformation in patients with essential hypertension, depending on the presence of left ventricular (LV) diastolic dysfunction (DD).

Materials and methods

114 hypertensive patients (40 women and 74 men) were involved in the study. The average age of the patients was 42±8.3 years. The diagnosis was confirmed by a thorough clinical and instrumental examination. Patients had no CVD or renal disease. LV diastolic filling parameters were assessed according to ASE/EACVI criteria (2016). The indicators of myocardial deformation were studied as well. The level of MMP1, MMP2 and TIMP was assessed by the method of enzyme-linked immunosorbent assay. Statistical methods such as Cruskell-Walles criteria and Spearman's correlation coefficient were used.

Results

1st group consisted of 66 patients with normal LV filling parameters, 2nd group was represented by 48 patients with LV DD, control group consisted of 35 healthy men and women, matching by age.

The level of MMP1 in group 2 was increased by 112% compared with group 1 and by 117% compared with the control group (101.1±10.4, 47.7±13.2 ng/ml and 46.6±26.1 ng/ml, respectively, p<0.01). In group 2 patients, there was an increased level of MMP2 by 107% compared with patients in group 1 and by 112% compared with the control group (2519.0±233.9 ng/ml, 1216.1±189.8 ng/ml and 1186, 9±64.0 ng/ml, respectively, p<0.01). The TIMP level was higher in hypertensive patients with LV DD: 2.3 times higher than in the group of patients without diastole disturbance, and 2.4 times higher than in the control group (158±24 ng/ml, 68.2±18.8 ng/ml and 66.3±14.0 ng/ml, respectively, p<0.05). Differences between groups 1 and controls were not found for any of the studied parameters.

The study of global longitudinal myocardial deformation (Avg) depending on the presence of LV DD showed that in the 2nd group patients this indicator was 22.8% lower than in 1st group patients (p<0.05). Compared with healthy people in groups 1 and 2, there was a decrease in Avg by 23.3% and 40.7%, respectively (p<0.05). The analysis revealed a moderate negative correlation between the global longitudinal LV deformity and the level of MMP2 (r=−0.64, p<0.05).

Conclusion

Thus, in hypertensive patients with LV DD, an increase in the level of MMP1, MMP2, and TIMP interrelated with global myocardial deformation was revealed, which suggests the participation of these markers in the formation of impaired LV diastolic filling in hypertension.

Funding Acknowledgement

Type of funding sources: None.
Renal biomarkers reflect overall hypertensive organ damage: “one organ to rule them all”
Authors: Terentes-Printzios D , Aznaouridis K , Ioakeimidis N , Gardikioti V , Xaplanteris P , Georgakopoulos C , Dima I , Oikonomou D , Tsioufis K , Vlachopoulos C
Published: October 2021

Background/Introduction

Hypertension is associated with higher cardiovascular risk as well as several markers of subclinical target organ damage (TOD). Albumin to creatinine ratio (ACR) in urine has been recognized as an independent risk factor for cardiovascular events.

Purpose

We hypothesized that there is a relationship between ACR and markers of TOD in never-treated hypertensives.

Methods

We enrolled 924 consecutive essential hypertensives (mean age 53±12 years, 486 males) without known cardiovascular disease (CVD). Markers of subclinical TOD [left ventricular mass index (LVMI), pulse wave velocity (PWV), ankle-brachial index (ABI) and estimated glomerular filtration rate (eGFR)] were evaluated in all patients. LVMI was assessed echocardiographically using the Devereux formula. Carotid-femoral PWV was estimated with the Complior device. eGFR was calculated by the Cockcroft-Gault formula. ABI was calculated by dividing the highest ankle systolic blood pressure by the highest brachial systolic blood pressure.

Results

ACR exhibited significant association with LVMI (r=0.277, p<0.001, Figure), PWV (r=0.277, p<0.001) ABI (r=−0.078, p=0.018) and eGFR (r=−0.100, p=0.002). In further analysis, ACR was associated with TOD as suggested by the 2018 European Guidelines for Hypertension [left ventricular hypertrophy (LVMI>115 g/m2 in men and >95 g/m2 in women), increased PWV (PWV>10m/s), decreased ABI (ABI<0.9) and decreased renal function (eGFR<60ml/min)]. Specifically, ACR exhibited significant association with the number of TOD and this association was independent of age and gender (p<0.05).

Conclusions

Our findings support the close relationship between ACR and TOD in hypertension, as well as, the predictive ability of ACR for TOD.

Funding Acknowledgement

Type of funding sources: None. Association between LVMI and ACR
Factors of adherence to lifestyle modification in older patients with cardiovascular comorbidity
Authors: Efremova E , Shutov A M , Skorodumova E G
Published: October 2021

Lifestyle modification is one of the leading strategies for successful therapy. Older patients are characterized by comorbidity and gerontological syndromes that result in low adherence to lifestyle modifications. The aim of this study was to investigate the factors of adherence to lifestyle modification in older patients with cardiovascular comorbidity.

Materials and methods

344 older patients with cardiovascular disease (171 females, mean age 69,5±7,6 years) were examined. Arterial hypertension had 330 (95,9%) patients, coronary heart disease - 298 (86,6%), chronic heart failure - 240 (69,8%), diabetes mellitus – 100 (29%). Arterial hypertension was defined according to ESC Guidelines for the diagnosis and treatment of arterial hypertension, 2018. An integral indicator of adherence to a healthy lifestyle was assessed, including smoking status, physical activity, consumption of fruits and vegetables, and salt restriction. The level of education, income, personal profile (MMPI scale), cognitive status (MMSE scale) were estimated.

Results

145 (42.2%) older patients with cardiovascular comorbidity had high and satisfactory adherence to lifestyle modification. Women more often had a high and satisfactory adherence to adherence to lifestyle modification compared to men: 85 (49.7%) and 60 (34.6%), resp., χ2=7.96; p=0.005. The presence of diabetes mellitus was associated with high and satisfactory adherence to lifestyle modification (OR 2.39; 95% CI 1.29–4.42; p=0.005). Older patients with high adherence to lifestyle recommendations had a higher MMSE score (26.9±2.7 and 24.7±3.7 scores, resp., p=0.01) and lower personality profile indices on the depression scale (MMPI) (52.2±9.8 and 60.6±11.1 T-scores, resp., p=0.01) compared to patients with low adherence. There were no differences from education, income, and marital status (p>0.05). When constructing classification trees in older patients with cardiovascular comorbidity diabetes mellitus was an independent factor for satisfactory and high adherence to lifestyle modification, in the absence - female sex (sensitivity - 84.8%; specificity - 37.5% (AUC = 0.64); p=0.001 for model; χ2=20.2, p=0.0002).

Conclusions

More than half of older patients with cardiovascular comorbidity are characterized by low adherence to lifestyle modification. Diabetes mellitus is the most significant predictor of a high degree of adherence to lifestyle modification in older patients with cardiovascular comorbidity.

Funding Acknowledgement

Type of funding sources: None.
Antihypertensive medication and outcome in patients with COVID-19 compared to non-COVID respiratory infections
Authors: Blum S , Lampart M , Zhou Q , Mueller C , Osswald S , Kuster G M , Twerenbold R
Published: October 2021

Background

Recent reports suggested no adverse effects of antihypertensive medication including inhibitors of the renin-angiotensin system on outcome of patients with coronavirus disease 19 (COVID-19). However, most of these studies lack adequate control groups, and regional and socio-economic differences may additionally affect clinical course and outcome of COVID-19.

Methods

In the prospective observational cohort COrona VIrus surviVAl (COVIVA) study at our university hospital, we consecutively enrolled patients presenting to the emergency department with symptoms suggestive of COVID-19 between March and June 2020. Patients tested positive for COVID-19 (cases) were compared with patients tested negative, who had a respiratory infection (respiratory control). Primary outcome measure was the composite of ICU admission, 3'-day mortality or rehospitalization for respiratory symptoms.

Results

The final analysis consisted of 191 patients with COVID-19 and 323 respiratory controls. Sixty cases (31.4%) and 87 (26.9%) respiratory control patients were on ACE inhibitors (ACE-I) or angiotensin II receptor blockers (ARB). In unadjusted models the hazard ratio [95% CI] for the composite outcome for patients on ACE-I/ARBs was 2.36 [1.34; 4.16], p=0.003 and 2.05 [1.03; 4.09], p=0.04 among patients with COVID-19 and respiratory controls, respectively. The corresponding multivariable adjusted HRs were 1.32 [0.68; 2.55], p=0.41 and 1.20 [0.58; 2.48], p=0.62. Furthermore, we did not observe an increased risk for the outcome when assessing ACE-Is and ARBs separately or other antihypertensive agents, both in COVID-19 patients and respiratory controls (Table).

Conclusions

In a Swiss cohort of patients with COVID-19 or non-COVID respiratory controls treatment with ACE-I/ARBs or other antihypertensive medication was not associated with adverse events after accounting for comorbidities and risk factors.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Foundation for Cardiovascular Research Basel (FCVR Basel)Swiss Heart Foundation
Clinical and radiological testing for subclinical atherosclerosis in first-degree relatives of patients with premature coronary artery disease: feasibility and diagnostic yield
Authors: Vikulova D , Bevanda L , Pimstone S N , Brunham L R
Published: October 2021

Background

Premature atherosclerotic cardiovascular disease (ASCVD) is highly heritable. The screening of first-degree relatives (FDR) of patients with premature ASCVD is recommended but not routinely performed, and the diagnostic yield of different approaches to such screening is unknown.

Purpose

To determine the feasibility and diagnostic yield of clinical and radiological screening of FDRs of patients with premature coronary artery disease (CAD) in clinical setting.

Method

We recruited FDRs of patients with angiographically-proven CAD with stenosis of ≥50% who presented at the age of ≤50 years for males and ≤55 years for females. After clinical and laboratory assessment, patients with no personal history of cardiovascular disease underwent either coronary computed tomography angiography (CCTA), coronary calcium scoring assessment (CAC), or carotid ultrasound (CUS). Subclinical atherosclerosis was defined as 1) CAC score >100 Agatston units or >75% percentile for age and sex; 2) Stenosis >50% in at least one coronary artery or segment involvement scores >50th percentile in males and >75th in females; or, 3) Carotid plaque on ultrasonography.

Results

We enrolled 220 FDRs between 2017 and 2020, 129 completed clinical assessment (Figure 1). Of them, 28 (21.7%) had a personal history of ASCVD and 101 were tested for subclinical atherosclerosis. The characteristics of these patients are shown in Table 1. The most prevalent cardiovascular risk factors were dyslipidemia (40.6%), hypertension (22.8%), and obesity (21.8%). When assessed with the Framingham risk score calculator without adjustment for family history, only 5.1% and 28.6%, of patients had high or moderate cardiovascular risk, respectively. After adjusting for family history and the presence of statin-indicated conditions, 39.6% and 14.9% of patients were placed in high and moderate risk groups, respectively. Subclinical atherosclerosis was found in 43.6% of all patients (Figure 1) and 57.7% of patients over 40 years of age. The diagnostic yield of procedures was 29.6% for CUS, 37.8% for CCTA and 61.1% for CAC scoring. After the radiological assessment, 13.9% of patients were reclassified to a higher risk group (Table 1).

Conclusion

Non-invasive cardiovascular imaging detected subclinical atherosclerosis in 43.6% of healthy patients with a family history of premature ASCVD, moving 1 in 7 patients to a higher risk group and suggesting that this screening approach may improve risk prediction in this population.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research.St. Paul's Hospital Foundation and the Vancouver General Hospital Foundation. Figure 1Table 1
Mild renal dysfunction is associated with increased risk of ischemic heart disease disease among healthy adults
Authors: Tiosano S , Fardman A , Kaplan A , Kalstein M , Moshkovits Y , Segev S , Beckerman P , Segev A , Grossman E , Maor E
Published: October 2021

Introduction

The relationship between ischemic heart disease (IHD) and advanced chronic kidney disease is well established. However, there is a paucity of data regarding the long-term association in between renal function and incidence of IHD.

Purpose

To study the remote association between point renal function and future incidence of ischemic heart disease among healthy adults.

Methods

We evaluated asymptomatic self-referred adults who participated in a medical screening program. All subjects were free of IHD at baseline. Glomerular Filtration Rate (GFR) was calculated by CKD-EPI and divided into quartiles (Q1 represents the lowest quartile). Study endpoint was the development of IHD which was externally adjudicated by a physician. Mortality data were available for all subjects from national registry. Cox regression models were applied while adjusting for confounders.

Results

The final study population included 27,647 subjects (68% men) with a mean age of 47 years. At baseline (first screening visit), median GFR by CKD-EPI was 84 [IQR 74; 95] and 86 [IQR 74.; 101] mL/min per 1.73m2 for men women, respectively. During median follow up of 6 years [IQR 2; 12], 2,286 (8%) of subjects developed IHD, of whom 1,912 (10%) were men and 374 (4%) were women. Incident IHD was in 964 (13.98%), 705 (10.22%), 437 (6.34%) and 171 (2.48%) subjects from GFR Q1-Q4, respectively. Kaplan Meier survival analysis demonstrated a graded increased risk of IHD with decreasing eGFR quartiles (p Log rank <.001; Figure 1). Multivariate cox regression analysis revealed hazard ratio of 1.26 (95% CI 1.06, 1.51), 1.43 (95% CI 1.20, 1.70), and 1.25 (1.05, 1.50) for IHD incidence for Q1-Q3, respectively (using Q4 as reference). While considering GFR as a continuous variable, each 10 units increase in GFR was significantly associated with 4% less risk for developing IHD - HR 0.96 (95% CI 0.93–1.00, p=0.04).

Conclusion

Mild renal dysfunction even within the normal range is independently associated with remote risk of IHD among young apparently healthy adults. Cardiovascular screening should be considered among young patients with reduced renal function, even within normal reference range.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Association of nephronophthisis 4 genetic variation with cardiorenal syndrome and cardiovascular events in Japanese general population: the Yamagata (Takahata) study
Authors: Otaki Y , Watanabe T W , Goto J G , Saito Y S , Aono T A , Kobayashi Y K , Sato J S , Watanabe M W
Published: October 2021

Background

Nephronophthisis (NPHP) 4 gene encoding nephrocystin-4, which contributes to end-stage renal disease in children and young adults, is involved in the development of the heart and kidneys. Cardiorenal syndrome (CRS), which consists of bidirectional dysfunction of the heart and kidneys, is a risk factor for cardiovascular events. Single nucleotide polymorphisms (SNPs) within the NPHP4 gene are reportedly associated with kidney function, even in adults. However, the association of NPHP4 gene variability with CRS and cardiovascular events remains unknown.

Purpose

To examine whether NPHP4 gene variability is related to CRS and cardiovascular events in general population.

Methods and results

This prospective cohort study included 2,946 subjects who participated in a community-based health study with a 16-year follow-up period. We genotyped 11 SNPs within the NPHP4 gene whose minor allele frequency was greater than 0.1 in the Japanese population. The SNP rs12058375 was significantly associated with CRS and cardiovascular events. Multivariate logistic analysis demonstrated a significant association between the homozygous A-allele of rs12058375 with the presence of CRS. Haplotype analysis identified the haplotype with the A-allele of rs12058375 as an increased susceptibility factor for CRS. Kaplan-Meier analysis demonstrated that homozygous A-allele carriers of rs12058375 had the greatest risk of developing cardiovascular events among the NPHP4 variants. Multivariate Cox proportional hazard regression analysis revealed that the homozygous A-allele and heterozygous carriers of rs12058375 were associated with cardiovascular events after adjusting for confounding factors. The net reclassification index and integrated discrimination index were significantly improved by the addition of rs12058375 as a cardiovascular risk factor.

Conclusion

Genetic variations in the NPHP4 gene were associated with CRS and cardiovascular events in the general population, suggesting that it may facilitate the early identification of high-risk subjects with CRS and cardiovascular events.

Funding Acknowledgement

Type of funding sources: None.
HbA1c, coronary atheroma progression and cardiovascular events
Authors: Dykun I , Bayturan O , Carlo J , Nissen S E , Nicholls S J , Puri R
Published: October 2021

Background

Hemoglobin A1c (HbA1c) reflects long-term glycemic control and is associated with an increased risk of cardiovascular events among diabetic and non-diabetic patients. The specific impact of HbA1c upon atheroma progression and incident cardiovascular events relative to the presence of other cardiovascular risk factors remains uncertain.

Purpose

We tested the hypothesis that on-treatment HbA1c levels independently associate with coronary atheroma progression measured with serial intravascular ultrasonography (IVUS) and major adverse cardiovascular events (MACE: death, myocardial infarction, cerebrovascular accident, coronary revascularization, or hospitalization for unstable angina) rates.

Methods

We performed a post-hoc pooled analysis of data from eight prospective, randomized trials involving serial coronary IVUS. HbA1c was measured at baseline and the average of the follow-up values was taken. The percent atheroma volume (PAV) was calculated as the proportion of the entire vessel wall occupied by atherosclerotic plaque, throughout the segment of interest. Using multivariable mixed modeling, we determined the association of HbA1c with annualized change in PAV. Cox proportional hazard models were used to assess the association of HbA1c with incidence of MACE.

Results

Among 2,791 patients, mean age was 58.9±9 years and 29.1% were women. Mean on-treatment low-density lipoprotein (LDL)-cholesterol was 80.2±33.7 mg/dl and median on-treatment triglycerides (TG) were 125.5 (94.7, 170.2) mg/dl. Mean baseline and follow-up HbA1c was 6.2±1.2% and 6.3±1.2%, respectively. Overall, there was no net significant annualized change in PAV (0.15±0.21, p=0.47). In a fully adjusted multivariable analysis (following adjustment of age, sex, body mass index (BMI), systolic blood pressure, smoking, LDL- and high-density lipoprotein cholesterol, TG levels, peripheral artery disease, trial, region, and baseline PAV), higher on-treatment HbA1c levels were independently associated with annualized changes in PAV [beta-estimate (95% confidence interval): 0.13 (0.07, 0.19), p<0.001]. On-treatment HbA1c levels were significantly and independently associated with incidence of MACE [hazard ratio (95% confidence interval): 1.17 (1.07, 1.28), p<0.001].

Conclusions

Independent of achieved cholesterol levels, vascular risk factors and BMI, greater HbA1c levels significantly associate with coronary atheroma progression and clinical outcomes. These results support the notion of a direct, specific effect of glycemic control upon the natural history of coronary atheroma and atherosclerotic events, supporting the rationale of therapies designed to directly modulate it.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Iryna Dykun was supported by the German Research Foundation
Anticipating recurrent ischemic events after an acute coronary syndrome: validation and application of the SMART-REACH score
Authors: Gomes D , Presume J , Albuquerque F , Lopes P , Sousa Paiva M , Reis Santos R , Aguiar C , Ferreira J , Trabulo M , Mendes M
Published: October 2021

Background

The SMART-REACH score (SRS) was developed to predict the risk of major adverse cardiovascular events in ambulatory patients with established cardiovascular disease, although it has not been extensively validated. Patients at higher risk of recurrent ischemic events may benefit from novel, more intensive treatment options, and earlier identification of these patients can potentially improve outcomes.

Purpose

We aimed to validate the SRS and evaluate its performance in a population recently admitted with acute coronary syndrome.

Methods

In this single-centre retrospective cohort, we included 320 patients aged 45 to 80 years, who were discharged following admission for an acute coronary syndrome between 2016 and 2018. To calculate the SRS for each patient, we considered clinical data on admission (age, gender, smoking, diabetes, prior history of vascular disease, heart failure or atrial fibrillation), lipid values obtained within the first 24 hours of hospitalization, serum creatinine level at baseline and once the patient was deemed clinically stable, and discharge medication. The outcome of interest was defined as stroke, myocardial infarction or cardiovascular death (MACE) at two years of follow-up. SRS was assessed for discrimination and calibration.

Results

Mean age was 63±9 years, and 240 (75%) were male. There was high prevalence of cardiovascular risk factors: 71% had hypertension, 32% had diabetes mellitus, 42% were active smokers and 25% had previously established cardiovascular disease. The outcome of interest was observed in 38 patients (22 cardiovascular deaths, 6 strokes and 14 myocardial infarctions). SRS showed good discrimination of the estimated MACE risk with overall C-statistic of 0.646 (95% CI, 0.554–0.737, p=0.004) (picture 1) and calibration (p-value for the goodness-of-fit test of 0.544). The global estimated risk of MACE at 2-years was 4.8% (3.8%-6.8%). The expected/ observed ratio was 0.56 for the occurrence MACE (picture 2).

Conclusions

Over the first two years after discharge from an acute coronary syndrome, one of every 8 patients developed a potentially fatal recurrent ischemic event. The SRS performed reasonably well in discriminating those at highest risk of MACE, suggesting that this score may help select patients at discharge for ad initium more intensive pharmacological therapy.

Funding Acknowledgement

Type of funding sources: None. ROC curve for the SMART-REACH scoreExpected versus observed MACE
Prediction of congestive heart failure in patients using artificial intelligence: proof of concept
Authors: Pana M , Vasilescu E I , Busnatu S S , Andrei C , Popescu N A , Sinescu C J
Published: October 2021

Introduction

Due to the aging of the population we are confronting ourselves with an increased number of patients with chronic heart failure which stands a prevalence of over 37,7 million cases worldwide, being a major public health issue, first by the substantial morbidity and mortality that carries and second by the economic burden it brings annually upon the health-care system.

The main purpose of this study is to test a machine learning algorithm which can predict, through voice analysis the acutisation of heart failure, considering the particularities of the patient's voice.

Methods

The data we have used has been collected from a total of 16 patients, 9 men and 7 women, ages between 65 and 91 years old, who have agreed to take part in the study.

The selective criteria of inclusion has been the cause of hospitalization, selecting only the patients presented with cardiogenic acute pulmonary edema, regardless the precipitation cause or other known cardiovascular comorbidities. With the same electronic device we have recorded each patient's voice, twice a day, starting from the day one of hospitalization, when their general status was critical, until the day of discharge, when they were clinically stable.

Each voice recording containing specific keywords has been associated to the most used classification system for heart failure, the New York Heart Association Functional Classification and introduced into the machine learning algorithm.

Results

After integrating the information from 15 patients, the algorithm has classified correctly the 16th patient into the third NYHA stage, based only on his voice recording.

Conclusion

Voice is a cheap and easy way to monitor a patient's health status. The algorithm we have used for analyzing the voice provides high accuracy results, but for a larger dataset it might not be the best choice as it is computationally expensive. We are looking to obtain larger datasets and to compute more complex voice analyzer algorithms.

Funding Acknowledgement

Type of funding sources: None.
Prevalence, genotype and phenotype of familial hypercholesterolemia in 10,194 Finnish men
Authors: Korhonen L , Maria M , Vangipurapu J , Laakso M , Kuusisto J
Published: October 2021

Background

Familial hypercholesterolemia (FH) is the most frequent monogenic disease with an estimated prevalence of 1:250. The prevalence of different variants varies widely between the populations. According to previous studies, the prevalence of heterozygous FH in Finland has been reported to be 1:400–650, seven Finnish LDLR founder mutations having been considered to cause 80% of FH.

Purpose

To investigate the genetics of FH in the large Finnish population-based study.

Methods

The whole exome sequencing using Next Generation Sequencing method was performed for 10,194 men from eastern Finland who participated in the METSIM (Metabolic Syndrome in Men) study. The findings were confirmed by Sanger sequencing. The coding regions of the FH causing genes LDLR, APOB and PCSK9 were sequenced. The pathogenicity of the variants was classified according to the ACMG guidelines, and using the Genome Aggregation Database (gnomAD), and the ClinVar archive.

Results

Total 22 individuals of 10,194 carry 8 different pathogenic/likely pathogenic (P/LP) FH variants (7 LDLR variants, 1 APOB variant and 0 PCK9 variants). Seven LDLR gene variants classified as P/LP were detected in 21 individuals. Two of the seven variants are founder mutations (p.Pro309Lysfs*59, p.Arg595Gln), four are other previously reported variants (p.Arg124Trp, p.Glu228*, p.Asp266Asn, p.Asp445Glu) and one is a novel variant (p.Gly396Ala). Of the 21 individuals carrying P/LP LDLR variants, 16 carry founder mutations and five other P/LP LDLR variants. Of individuals carrying any P/LP LDLR variant, 28.6% had premature (men <55 years, women <60 years) atherosclerotic cardiovascular disease (CVD): coronary artery disease (CAD) 28.6%, peripheral artery disease (PAD) 0.0%, and stroke or TIA 0.0%. CVD at any age was diagnosed in 38.1% (CAD 33.3%, PAD 4.8%, stroke or TIA 9.5%). Only one individual from 10,194 carry APOB variant which is classified as P/LP. The detected APOB variant is a previously reported variant (p.Gln4494del). None of the 10,194 individuals carry P/LP PCSK9 variants. Thus, the prevalence of P/LP FH variants in the population from eastern Finland was 0.22%, 1 in 463.4 (LDLR variants 0.21%, 1 in 485; APOB variants 0.01%, 1 in 10 194). Of the P/LP variant carriers, 72.7% carry founder mutation of the LDLR, and 27.3% carry other LDLR and APOB variants.

Conclusions

The prevalence of heterozygous FH in the population-based study of 10,194 men from eastern Finland was 1 in 463.4, which is about the same as previously reported. LDLR variants accounted for the majority of FH cases, and although previously reported Finnish LDLR founder mutations were common, about 30% of the mutations detected were other LDLR and APOB variants. Pathogenic/likely pathogenic APOB variants were, however, rare and PCSK9 variants were not found.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Kuopio university hospital
The frequency and profile of lipid lowering treatment in a contemporary Russian population
Authors: Ryabikov A , Mazdorova E , Shapkina M , Avdeeva E , Simonova G , Hubacek J A , Bobak M , Malyutina S ,   The HAPIEE Group
Published: October 2021

Background

Despite of guidelines for management of dyslipidemias (DLP) and the availability of effective and safe lipid lowering drugs (LLD), about one half of CVD patients do not reach the target lipid levels. The knowledge on DLP management in Russian population is limited.

Objective

To analyze the frequency and profile of LLD therapy in subjects with DLP and cardiometabolic diseases in a contemporary Russian population.

Methods

A random population sample of men and women 55–84 years old (n=3898) was examined in 2015–17 in the Russian arm of the HAPIEE project. A composite dysmetabolic group included DLP (total cholesterol, TC ≥5 mmo/l or low-density lipoprotein cholesterol, LDLC ≥3 mmol/l or triglycerides, TG ≥1.7 mmol/l) and/or coronary heart disease (CHD) and/or diabetes mellitus type 2 (DM2). Regular medication intake for 12 months was coded by ATC.

Results

In studied population sample 88% of subjects had dysmetabolic disorders (DLP - 83.1%, CHD - 14.9%, DM2- 20.8%); among them 32.8% subjects received LLD therapy (21.2% in men vs. 39.4% in women, p<0.001) and 17.1% did not report the status of LLD receiving. The frequency of LLD use in CHD group was 48,3%, in DM2 – 35,0%, in DLP – 29.4%. Among named LLD, statins were predominantly used (98%). Lipids control was achieved among subjects with CHD in 18.3% (37.9% among those receiving LLD); among DM2 - in 9.0% (25.6%); among DLP without CHD or DM2 – in 7.3% (24.8%).

Conclusion

In an urban population sample aged 55–84 examined in 2015–17, more than one half of subjects with dysmetabolic disorders (CHD, DM2, DLP) did not receive LLD. Among those receiving lipid-lowering therapy, the lipid control was achieved in about 40% of participants with CHD, and in every forth participant with DM2 or DLP. The lack of lipid control is likely to contribute high rate of atherosclerotic CVD in studied population.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Russian Foundation of Basic Research; Russian Academy of Sciences
Obesity strongly predicts COVID-19-related major clinical adverse events in Coptic Clergy
Authors: Henein M Y , Bytyci I , Nicoll R , Rafik S , Ayad S , Vanchari F
Published: October 2021

Background and aims

The Coptic Clergy, due to their specific work involving interaction with many people, could be subjected to increased risk of infection from COVID-19. The aim of this study, a sub-study of the COVID-19-CVD international study of the impact of the pandemic on the cardiovascular system, was to assess the prevalence of COVID-19 among Coptic priests and identify predictors of clinical adverse events.

Methods

Participants were geographically divided into three groups: Group-I: Europe and USA, Group II: Northern Egypt and Group III: Southern Egypt. Participants' demographic indices, cardiovascular risk factors, possible source of infection, number of liturgies, infection management and major adverse events (MAEs), comprising death, re-infection or mechanical ventilation, were assessed.

Results

Out of the 1,570 clergy serving in 25 dioceses, 226 (14.39%) were infected. Their mean age was 49.5±12 years and mean weekly number of liturgies was 3.44±1.0. The overall prevalence rate was 14.7% and did not differ between Egypt as a whole and overseas (p=0.23). Disease prevalence was higher in Northern Egypt clergy compared to Europe and USA combined (18.4% vs 12.1%, p=0.03) and tended to be higher than in Southern Egypt (18.4% vs. 13.6%, p=0.09). Ten priests (4.42%) died of COVID-19 related complications, 2 (0.9%) had re-infection and 27 (11.9%) suffered a MAE. The clergy from Southern Egypt were more obese but the remaining risk factors were less prevalent compared to those in Europe and USA (p=0.01). In multivariate analysis, obesity OR 4.184 (2.483 to 12.14; p=0.01); age OR 1.070 (0.014 to 1.130; p=0.02), and systemic hypertension OR 0.932 (0.874 to 0.994; p=0.007) predicted MAEs. Obesity was the most powerful independent predictor of MAE in Southern Egypt and systemic hypertension in Northern Egypt (p<0.05 for both).

Conclusion

Obesity is very prevalent among Coptic clergy and seems to be the most powerful independent predictor of major COVID-19-related adverse events.

Funding Acknowledgement

Type of funding sources: None. Prevalence of SARS-CoV2 among Clergy
Prognosis of diabetes mellitus and timing of heart failure in patients with acute myocardial infarction. An analysis of a French nationwide hospital database
Authors: Fauchier L , Semaan C , Fauchier G , Herbert J , Genet T , Ivanes F , Ducluzeau P H , Angoulvant D , Danchin N
Published: October 2021

Background

Diabetes mellitus (DM) is a factor of increased mortality in patients with acute myocardial infarction (AMI). DM is also associated with a higher risk of heart failure (HF) in patients with coronary artery disease as in the general population. The aim of the present study was to assess the incidence of HF developing at the acute stage of MI and of HF occurring in the year following hospital discharge, according to presence of DM. We also assessed the association between DM, HF and long-term mortality in this AMI population.

Methods

We used the French administrative hospital-discharge database, including all patients without history of HF admitted for AMI between 2010 and 2019 (n=797,212, mean age 69 years, 66% male). Among them, 520,258 patients (65%) had ST-segment elevation myocardial infarction (STEMI), 276,954 (35%) had non-STEMI, 192,456 patients (24%) had a history of DM. Occurrence of HF during the initial hospital stay was analysed in the whole population. In patients without HF during the index hospitalisation, discharged and alive at day 8 (n=535,813), we collected all hospitalisations for HF occurring during the year after discharge and analysed subsequent long-term mortality in those alive at one year (n=270,534) (length of follow-up 2.0±2.5 years, median 0.9, IQR 0.1–3.5).

Results

Overall, DM patients were older than non-DM patients (71±12 vs 67±15 years) and had more frequent comorbidities. At the acute stage, DM was associated with a higher risk of HF (28.7% vs 20.5% adjusted OR 1.40, 1.38–1.42, p<0.0001). In patients without HF at the acute stage and discharged alive at day 8, DM was associated with a higher risk of being hospitalised with HF in the first year (5.6% vs 2.8%, adjusted HR 1.52, 1.49–1.56, p<0.0001). In patients alive at one year, rates of all-cause death per year during subsequent follow-up were 2.2% in those without DM or HF during the first year (reference), 3.4% in those with DM and no HF during the first year (adjusted HR 1.22, 1.18–1.25, p<0.0001), 7.7% in those without DM and with HF during the first year (adjusted HR 1.92, 1.83–2.02, p<0.0001) and 8.9% in those with DM hospitalised with HF during the first year (adjusted HR 2.23, 2.09–2.37, p<0.0001) (see figure).

Conclusion

After AMI, patients with diabetes are at increased risk of heart failure both at the acute stage and in the year following myocardial infarction, compared with non-diabetic patients. Non-fatal HF developing in the year following discharge is associated with noticeably higher subsequent mortality, and the combination of DM and HF is particularly at risk. Improved management is needed in diabetic patients following an AMI to avoid development of heart failure and its longer-term consequences.

Funding Acknowledgement

Type of funding sources: None.
Impact of thrombophilia and waist circumference on the risk of venousthromboembolism
Authors: Kondratieva T B , Popova L V , Khlevchuk T V , Kanevskaya M Z , Aksenova M B , Bokarev I N , Belenkov Y N , Golub A V , Ptrushev L I , Kovalenko T F , Gerasimov A N
Published: October 2021

Background

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE) represents a major health problem. In the general population, the absolute risk of any kind of VTE is 0.1%–0.2% per year, and it increases with age. VTE is an important and preventable cause of morbidity and mortality, with almost a third of survivors experiencing long term effects. Obesity is well-known risk factor of VTE. The extent of the effects of obesity on VTE depends not only on total body fat, but also on the distribution of adipose tissue (e.g., central obesity) and the interplay among risk factors for VTE, such as genetic mutations, and other risk factors.

Thrombophilia, venous thromboembolism, obesity, waist circumference

Purpose

The aim of this study is to investigate the impact of waist circumference on the risk of venous thromboembolism

Methodology

The study involved 68 patients with VTE (33 females and 34 males, mean age 56.8 years ±15.3) and 84 patients without VTE (38 males and 46 females, 44.4 years±18.6). From 2015 to 2017, data have been collected from records of patients admitted to department of internal medicine. All subjects were recruited to the study during their stay in the hospital. The reasons for hospitalization were: acute event of DVT or PE for the main group, the absence of acute event or history of VTE for the control group. DVT was diagnosed by ultrasonic Doppler examination, and PE was confirmed by intravenous radiocontrast computed tomography. Anthropometric measures were performed with subjects wearing short-sleeved garments and no shoes; waist circumference was measured in centimeters at the umbilical line. For all patients genetic testing for inherited thrombophilia – Factor V Leiden G1691A, Prothrombin G20210A, MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism – was performed by real-time PCR technique.

Results

Factor V Leiden G1691A increase the risk of VTE in 2.11 (CI: 1.79–2.48), p=0.049, prothrombin G20210A in 3.21 (CI: 1.66–6.211), p=0.049. MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism also increase the risk of VTE, but it was no significant. Study have shown that waist circumference >80 cm increase the risk of VTE in 3.19 (CI: 1.35–7.58), p=0.019. Combination of inherited thrombophilia (Factor V Leiden G1691A, Prothrombin G20210A, MTHFR C677T polymorphism, PAI-1 (SERPIN1) 4G/5G polymorphism) and waist circumference >80 cm increase the risk of VTE in 3.51 (CI: 1.76–7.04), p<0.001.

Conclusion

Previous results of our work indicate influence of waist circumference >80 cm on the risk of VTE, especially risk of thrombosis is higher in patients with combination inherited thrombophilia and waist circumference >80 cm.

Funding Acknowledgement

Type of funding sources: None.
Psychological profile of COVID-19 pneumonia survivors three month after hospitalization
Authors: Yaroslavskaya E , Guskova O , Prilenskii B , Petelina T
Published: October 2021

Background

COVID-19 is the highly contagious infectious disease, which affects different organs and systems. Anxiety and depression symptoms, that are common results of severe diseases, used to make recovery more difficult.

Purpose

To study the prevalence of cardiovascular diseases, signs of anxiety, depression, stress, and their relationship in patients with proven COVID-19 pneumonia 3 months after discharge depending of gender.

Methods

The study was carried out within “One-year Cardiac Follow-up of COVID-19 Pneumonia”. 103 patients (mean age 46.6±15.8 years) were divided into 2 groups: 52 men (50.9%) and 51 women. Anxiety and depression symptoms were measured by GAD-7 and PHQ-9, respectively. PSS-10 was used to measure stress symptoms. The minimum value of anxiety and depression was a total value of 5 points.

Results

48.5% of patients had cardiovascular diseases, out of which arterial hypertension (AH) was the most common (44.7%). Less common was coronary artery disease (CAD) (16.5%), which in 14.6% of patients was accompanied by AH. Chronic heart failure (CHF) NYHA class I-II was found in 19.4% of patients, and severe CHF (NYHA class III–IV) - in 4.9%. Arrhythmia was detected in 11.7% of patients. According to the clinical characteristics, no significant differences were found between the groups of men and women. AH affected 21.4% of men and 23.3% of women, CAD −10.7% and 5.8%, respectively. NYHA class I-II CHF were found in 8.7% of men and 10.7% of women, and severe CHF (NYHA class III–IV) - in 2 men and 3 women. Arrhythmia had a prevalence of less than 6% among both men and women. Anxiety or depression symptoms were reported in 29.1% and 27.2%, respectively. Combination of anxiety and depression symptoms was determined in 18.4%, symptoms of stress in 8.7% of patients. Symptoms of depression were found in women more often (p=0.023). The value of the median scores of the PHQ-9 questionnaire in the group of women was significantly higher than in the group of men (3.00 [1.00; 8.00] and 1.00 [0; 3.75], p=0.006). Depression symptoms were associated with female gender (OR 2.83; CI 95% 1.35–7.08). Despite the absence of gender differences in the prevalence of anxiety (18.4% and 10.7%, p=0.072), when comparing the values of the median scores of the GAD-7 questionnaire in the groups of men and women, the difference was statistically significant (1.00 [0; 4.00] and 3.00 [2.00; 7.00], p=0.001, respectively). Signs of stress among married people were less common in comparison with unmarried (2.9% vs 5.8%, p=0.037).

Conclusion

Three months after discharge, no significant differences in clinical characteristics between men and women were found. Signs of anxiety or depression were detected in more than a quarter of patients with proven COVID-19-associated pneumonia. Women experienced symptoms of depression 3 times more often than men. Unmarried patients tended to experience stress more often.

Funding Acknowledgement

Type of funding sources: None.
Hybrid cardiac telerehabilitation program as a potential strengthening factor in the quality of life in patients with coronary heart disease: a retrospective single-centre analysis
Authors: Cabral M , Santos R , Januario F , Antunes A , Pinto R F , Morais J
Published: October 2021

Cardiac rehabilitation (CR) has well known beneficial effects on physical capacity, health-related quality of life, morbidity and mortality in patients with coronary artery disease (CAD). However, underuse of CR and not sustained improvements have been noted. It has been proposed that telemonitored exercise-based CR, by the use of mobile applications, can improve patient adherence to CR programs providing better outcomes.

The aim of this study was to investigate the effects of telemonitored cardiac rehabilitation on physical capacity, health-related quality of life and control of cardiovascular risk factors among patients with CAD on phase 2 of the Cardiac Rehabilitation Program (CRP).

A retrospective study was conducted and patients in CRP between 2017 and 2020 were included. Patient selection and information collection were obtained through medical records. Outcomes were Body Mass Index, Hospital Anxiety and Depression Scale (HADS), EuroQol-5D score (EQ-5D), International Physical Activity Questionnaire (IPAQ), estimated functional capacity in cardiac stress test, lipid panel and glycated hemoglobin. Patients were divided into two groups: group 1 followed the conventional strategy and group 2 followed a hybrid telemonitored CRP, with the use of MOVIDA mobile application. Variables were analysed in the beginning (T0) and in the end (T1) of the phase 2, around 3 months after. Group comparisons tests and multivariate logistic regression were performed. A p-value less than 0.05 is statistically significant. Statistical analysis was performed using SPSS software v25.0.

We analysed 107 patients, which 93 of these were assiduous and 69 concluded the phase 2 of CRP: 44 patients in group 1 and 25 patients in group 2. Two groups have similar baseline characteristics, except for age (p=0.02). It appears that participation in the PRC led to an improvement in physical capacity, mental well-being, and in lipid panel, regardless of the strategy. The improvement in quality of life, quantified by EQ-5D, was significant only in group 2 (p=0.03). There is also no correlation between age and the differences recorded in EQ-5D (p=0.86).

We hypothesise that, when compared to conventional CRP, cardiac telemonitored exercise using modern communication methods and on-demand coaching will result in an improved behavioural change, which translates to higher quality of life. Further studies including more patients and the phase 3 of CRP are needed to confirm these results.

Funding Acknowledgement

Type of funding sources: None.
Long-term prediction of mortality and comparative treatment benefit following percutaneous or surgical revascularization
Authors: Hara H , Shiomi H , Van Klaveren D , Kent D , Steyerberg E W , Garg S , Onuma Y , Kimura T , Serruys P W
Published: October 2021

Background

The SYNTAX score II 2020 (SSII-2020), which was derived and externally validated from randomized trials, was designed to predict death following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel disease and/or left main disease. We aimed to investigate its value in identifying the safest modality of revascularization in a non-randomized setting.

Methods

Five-year mortality was assessed in 7362 patients with three-vessel disease and/or left main disease enrolled in a Japanese PCI/CABG registry. New-generation drug eluting stents and imaging guidance became the default PCI strategy during enrolment of the last cohort. The discriminative ability of the SSII-2020 for 5-year mortality was assessed using Harrell's C statistic (C-index). Agreement between observed and predicted rates of all-cause mortality following either PCI or CABG and treatment benefit (absolute risk difference) for this outcome were assessed by calibration plots.

Results

The SSII-2020 had helpful discrimination (C-index = 0.72) and good calibration (intercept = −0.11, slope = 0.92) for 5-year mortality. The absolute risk difference in mortality between CABG and PCI (treatment benefit) was well calibrated when the whole population was grouped into quarters according to the predicted absolute risk difference of 5-year mortality. The observed differences in survival in favor of CABG were 4.2% (0.1 to 8.2%, log-rank p=0.05) and 8.5% (3.8 to 13.2%, log-rank p<0.01) in the respective third and fourth quarters. In contrast, the observed differences in survival were not significantly different in either the first (3.0% [−0.8 to 6.8%, log-rank p=0.12]) or the second quarter (1.3% [−2.4 to 5.1%, log-rank p=0.39]).

Conclusions

The SSII-2020 is well able to predict death at 5 years – and the mortality difference between PCI and CABG, and therefore has the potential to support decision making on revascularization in patients with three-vessel disease and/or left main coronary artery disease.

Funding Acknowledgement

Type of funding sources: None.