bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential benefits of antihypertensive therapy in NAFLD: results from an experimental model
Authors: Soares Sturzeneker M.C , Precoma D.B , Noronha L , Olandoski M , Broday G.A , Scheidt B.J , Oliveira P.G.M , Viechineski F.N , Koscianski A.M
Published: November 2020

Background and introduction

Non-alcoholic fatty liver disease (NAFLD) is considered as the most frequent cause of chronic hepatic disease in adults. It is strictly correlated with insulin resistance. The renin-angiotensin system (RAS) has been correlated to the whole basic physiopathogenic mechanism of NAFLD in experimental models. Systemic arterial hypertension has been suggested to be associated with NAFLD in approximately 40% of the cases, and NAFLD has been independently associated with an increased risk of arterial hypertension in observational studies. Therefore, we can infer that treating arterial hypertension in NAFLD carriers will often be necessary and that the potential beneficial effects of the antihypertensive might, in this context, influence the choice of the respective drug.

Purpose

We aimed to evaluate the effects of the renin-angiotensin system blockade with angiotensin-converting enzyme inhibitor ramipril and angiotensin 2 type 1 receptor antagonist olmesartan, both used preventively, in NAFLD induced in rabbits fed a hypercholesterolemic diet and compared the results between the groups.

Methods

Forty-one rabbits were divided into four groups (normal, control, olmesartan and ramipril). The control, olmesartan and ramipril group were fed a hypercholesterolemic diet. Animals from olmesartan group were treated with olmesartan 1mg/kg/day and animals from ramipril group with ramipril 0.35 mg/kg/day. At the end of the 8th week, all rabbits underwent segmental hepatic resection and were euthanised. Blood samples were collected to determine glucose, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and aminotransferase levels at baseline and euthanasia. Haematoxylin and eosin and Gomori trichrome stained slides were analysed based on the histological scoring system for NAFLD.

Results

The comparison between two groups (olmesartan with placebo and ramipril with placebo) showed that olmesartan and ramipril significantly diminished the development of steatosis (p=0.015, p=0.032), lobular inflammation (p<0.001, p=0.006), hepatocellular ballooning (p<0.001, p=0.023) and fibrosis (p=0.001, p=0.02). Based on NAFLD activity score, olmesartan and ramipril significantly reduced the development of nonalcoholic steatohepatitis (p<0.001, p=0.003). The comparison between olmesartan and ramipril showed that results were similar in all histological parameters evaluated (p=1, p=0.454, p=0.454, p=0.195, p=0.078).

Conclusion(s)

The preventive use of olmesartan and ramipril attenuates similarly, the development of hepatic steatosis, lobular inflammation, hepatocellular ballooning and fibrosis in hypercholesterolemic rabbits and based on NAFLD activity score both significantly reduced the development of nonalcoholic steatohepatitis.

Funding Acknowledgement

Type of funding source: None
Alcohol consumption patterns across Europe and adherence to the European guidelines in coronary patients: findings from the ESC-EORP EUROASPIRE V survey
Authors: Van De Luitgaarden I , Schrieks I , De Bacquer D , Van Oort S , Mirrakhimov E , Pogosova N , Davletov K , Dolzhenko M , Van Ballegooijen A , Kotseva K , Grobbee D , Beulens J
Published: November 2020

Introduction

Alcohol consumption is an important risk factor for cardiovascular morbidity and mortality worldwide. The highest levels of alcohol consumption are observed in Europe, where alcohol as contributing cause of coronary heart disease (CHD) is also most significant.

Purpose

To describe patterns of alcohol consumption across different European regions and adherence to the current drinking guidelines in coronary patients with a recent CHD.

Methods

The EUROASPIRE V survey has been conducted in 2016–2017 at 131 centers in 27 European countries in 9,018 patients with a recent CHD. Median alcohol consumption, as well as the proportions abstainers and excessive drinkers (i.e. >70 grams of alcohol per week for women and >140 grams per week for men, as recommended by the European guidelines on cardiovascular prevention), were calculated for each European region (Eastern, Southern, Northern and Western Europe). To assess adherence to guidelines, proportions of participants who were advised to reduce excessive alcohol consumption, as well as the participants who were incorrectly not advised were calculated per European region.

Results

Mean age was 64 years (sd=9.5), 75% was male. Abstention rates were 51% in males and 74% in females, whereas excessive drinking was reported by 10% of the males (highest in Western Europe (18%) and lowest in Eastern Europe (5%)) and 6% of the females (also highest in Western Europe (12%) and lowest in Eastern Europe (1.4%)). Overall, 57% of the participants were advised to reduce alcohol consumption. In the total population, 3% was incorrectly not advised (Figure 1), but this percentage differed by region with 9% in Western Europe as compared to 1% in Eastern Europe. In regions where alcohol consumption was highest, participants were less often advised to reduce their consumption.

Conclusion

In this EUROASPIRE V survey the majority of patients with a recent CHD adhere to the current drinking guidelines and only a fraction of the population was incorrectly not advised to reduce consumption. However, substantial heterogeneity exists between European regions.

Figure 1. Distribution of advice given per region

Funding Acknowledgement

Type of funding source: None
Early growth and carotid intima-media thickness at midlife: Northern Finland 1966 Birth Cohort study
Authors: Korpela N , Kaikkonen K , Auvinen J , Tulppo M.P , Junttila J , Perkiomaki J , Jarvelin M.R , Huikuri H.V , Kiviniemi A.M
Published: November 2020

Background

Carotid intima-media thickness (CIMT) reflects atherogenesis and is a strong predictor of cardiovascular diseases. Although cardiovascular diseases have been shown to originate in foetal life and childhood, the information on the contribution of early growth to CIMT in adulthood remains limited.

Purpose

To assess the influence of early growth patterns on CIMT in midlife.

Methods

A subpopulation of the Northern Finland Birth Cohort 1966 took part in follow-up, including CIMT evaluation by ultrasound (n=1155) at the age of 46 years. Maternal pre-pregnancy body mass index (BMI) was self-reported and birth weight and gestational age were measured after delivery. BMI growth curves were modelled based on frequent anthropometric measurements in infancy and childhood. Peak weight and height velocity in infancy (0–2 years of age, n=637) as well as age and BMI at adiposity peak (AP, mean age 9 months, n=461) and at adiposity rebound (AR, mean age 5.8 years, n=562) were established. Results are reported as unstandardized beta (β) with 95% confidence intervals for one standard deviation increase in early growth variable. Associations were adjusted for sex, birth weight, maternal pre-pregnancy BMI as well as adult weight, height, systolic blood pressure, low-density lipoprotein cholesterol, physical activity, diabetes, heart diseases and antihypertensive medication.

Results

Infant peak weight velocity (β=0.018 (0.011, 0.025), p<0.001) was associated with a higher CIMT in midlife, independently of adjustments for sex, early life factors and adult cardiometabolic factors (β=0.011 (0.003, 0.019), p=0.010). Infant peak height velocity was also associated with adult CIMT, but only in females (β=0.012 (0.004, 0.021), p=0.004) and the association was attenuated after adjustments (β=0.010 (0.0, 0.021), p=0.055). Birth weight and gestational age were not associated with adult CIMT. BMI at AP (β=0.011 (0.003, 0.019), p=0.007) and BMI at AR (β=0.010 (0.003, 0.018), p=0.005) were directly associated with CIMT in midlife in univariate analysis, but not independently of adult cardiometabolic factors. Timing of AP and AR were not related to adult CIMT. Finally, maternal pre-pregnancy BMI (β=0.005 (0.0, 0.011), p=0.066) also tended to be associated with a higher CIMT in midlife.

Conclusions

Rapid growth in infancy was the most important early growth-related factor associating with CIMT in midlife, and this relationship was not fully mediated by adult anthropometrics, cardiometabolic risk factors and morbidity.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Yrjö Jahnsson Foundation, Aarne Koskelo Foundation
Characteristics of patients with at least one lipoprotein(a) [Lp(a)] assessment and those with Lp(a) levels equal to or greater than 70 mg/dL: a real-world study in the US
Authors: Laguna A , Lahoz R , Fonseca A.F , Amari D.T , Ferber P , Heo J.H , Ding Y , Studer R
Published: November 2020

Background and purpose

Elevated lipoprotein(a) [Lp(a)] has been associated with increased risk of cardiovascular disease (CVD). The objective of this real-world study was to characterize the patients in the United States (US) that have an Lp(a) assessment and those with Lp(a) levels ≥70 mg/dL.

Methods

This is a descriptive, non-interventional, retrospective cohort study of patients with at least one Lp(a) assessment and one-year continuous enrollment prior to index date (first Lp(a) assessment in the identification period i.e. 1/1/2008–30/6/2019) using the Optum® de-identified Electronic Health Record (EHR) dataset (2007–2019) in the US. Optum's longitudinal EHR repository include more than 700 Hospitals and 7000 Clinics; treating more than 95 million patients receiving care in the US.

Results

26,997 patients (50.8% females) with ≥1 Lp(a) assessment having a mean (SD) age of 52.6 (14.1) years were evaluated. Patient distribution across Lp(a) levels ≥30, ≥50, ≥70, and ≥90 mg/dL were 32.4%, 20.2%, 12.3%, and 6.6%, respectively. Patients with Lp(a) ≥70 mg/dL (N=3,314) had a mean (SD) age of 54.7 (13.2) years and 55.2% were female. The overall population that gets tested for Lp(a) and the subgroup of patients with Lp(a) ≥70 mg/dL had prior myocardial infarction (4.8% and 6.2%), prior ischemic stroke (2.2% and 2.5%), peripheral artery disease (6.7% and 8.4%), dyslipidaemia (72.6% and 80.9%), hypertension (53.0% and 60.9%), diabetes mellitus (23.5% and 26.8%) and chronic ischemic heart disease (19.6% and 24.6%) at index. The use of baseline medications included statins (37.3% and 49.1%), ACEi/ARBs (28.2% and 34.0%) and beta-blockers (19.0% and 23.6%) for the overall population and those patients with Lp(a) ≥70 mg/dL, respectively.

The mean (SD) low-density lipoprotein cholesterol, triglycerides and total cholesterol levels were 109.8 (39.8) mg/dL [n=7,371], 138.3 (119.3) mg/dL [n=8,179] and 190.5 (46.8) mg/dL [n=8,181], respectively for overall population and 114.8 (41.5) mg/dL [n=980], 129.6 (80.5) mg/dL [n=1,063] and 195.9 (47.6) mg/dL [n=1,056] for patients with Lp(a) ≥70 mg/dL.

Conclusions

Of patients with an Lp(a) assessment in the US, more than 10% had Lp(a) levels ≥70 mg/dL. These patients were frequently diagnosed with dyslipidaemia and when reported showed elevated LDL-C and total cholesterol values. Further analyses are required to better understand any differences in patient characteristics and treatment of patients across Lp(a) levels.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Novartis Pharma AG
Depression in young adults is associated with increased carotid atherosclerotic burden: insights from the Corinthia study
Authors: Theofilis P , Oikonomou E , Vogiatzi G , Lazaros G , Tsalamandris S , Mystakidi V.C , Goliopoulou A , Fountoulakis P , Miliou A , Chasikidis C , Tousoulis D
Published: November 2020

Introduction

Depression appears to have a detrimental effect not only on mental health but also in the progression of various diseases.

Purpose

The examination of a potential association between depression and atherosclerosis progression in a rural population.

Methods

In the context of the cross-sectional Corinthia study, volunteers fulfilled a questionnaire concerning emotional health. The Geriatric Depression Scale was used for individuals aged 60 or more while the Zung self-rating depression score was preferred in younger adults. Carotid ultrasonography examination was performed to evaluate the mean carotid intima-media thickness (cIMT). Thickness of cIMT>1.5 mm or protrusion >50% compared to adjacent segments was considered as atherosclerotic plaque.

Results

Young adults with significant depression were usually female and did not differ significantly on other risk factors of atherosclerosis compared to those with mild or no depressive disorder. Importantly, those with moderate-severe depression appeared to have increased mean cIMT (Mild-No depression: 0.85±0.30mm, Moderate-severe depression: 0.91±0.42mm, p=0.04) and a higher carotid plaque burden (Mild-No depression: 12.8%, Moderate-severe depression: 20.3%, p=0.04). With regards to the elderly, those with moderate-severe depression were usually smokers (Mild-No depression: 13.9%, Moderate-severe depression: 24.2%, p=0.01). However, mean cIMT (Mild-No depression: 1.11±0.47mm, Moderate-severe depression: 1.09±0.39mm, p=0.69) and carotid plaques (Mild-No depression: 31.1%, Moderate-severe depression: 36.1%, p=0.36) did not differ according to depression status in this subgroup.

Conclusion

Significant depressive disorder is associated with accelerated carotid atherosclerosis in young individuals.

Funding Acknowledgement

Type of funding source: None
The role of dietary vitamin D intake on 10-year cardiovascular disease incidence, intermediate cardiometabolic risk factors and surrogate markers: highlights from ATTICA prospective study
Authors: Kouvari M , Panagiotakos D.B , Chrysohoou C , Yannakoulia M , Georgousopoulou E.N , Pitsavos C , Tousoulis D
Published: November 2020

Background/Introduction

Increasing vitamin D intake through food supplements or fortification is far from revealing strong contribution to cardiac health. On the other side, the separate evaluation of dietary vitamin D intake with cardiac health is limited.

Purpose

The aim of the present work was to evaluate the association between dietary vitamin D intake and 10-year first fatal/non fatal CVD, conventional CVD risk factors and surrogate markers related with inflammation, coagulation, insulin resistance, liver and renal function.

Methods

ATTICA prospective study was conducted during 2001–2012 and included n=1,514 men and n=1,528 women (aged >18 years old) from the greater Athens area, Greece. Dietary assessment was based on a validated semi-quantitative food frequency questionnaire. Daily intake of vitamin D was calculated through standardized food database. Follow-up assessment of CVD (2011–2012) was achieved in n=2,020 participants (n=317 cases).

Results

Ranking from 1st to 3rd vitamin D tertile, CVD event was for men 24%, 17% and 12% (p=0.002) and for women 14%, 10% and 11% (p=0.59), respectively. Multiadjusted analysis revealed inverse associations between vitamin D and CVD in total sample [Hazard Ratio (HR)=0.76 95% Confidence Interval (95% CI) (0.60, 0.97)] and in men [HR=0.66 95% CI (0.49, 0.89)], lost after adjusting for inflammation/coagulation markers; for women no significant trends against hard CVD endpoints were observed. Regarding 10-year onset of conventional risk factors, inverse associations of vitamin D with hypertension in men [HR=0.62 95% CI (0.39, 0.99)] and transition to metabolically unhealthy status in women [HR=0.69 95% CI (0.51, 0.93)] were observed. Multiadjusted analyses revealed significant inverse associations for C-reactive protein, interleukin-6 and fibrinogen in both sexes while only in women for insulin resistance.

Conclusions

Contradicting the neutral/modest associations in vitamin D supplementation trials, the present work revealed that increased food-generated vitamin D may protect against hard and intermediate CVD endpoints implying the existence of different paths between sexes.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): This work was supported by a research grant from Hellenic Atherosclerosis Society. The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].
Long-term outcomes evaluated by device-monitored physical activity in patients with implantable cardiac defibrillator or cardiac resynchronization therapy device
Authors: Yokomatsu T , Kato M , Hojo S , Kawaji T , Kushiyama A , Yaku H , Nakatsuma K , Kaneda K , Miki S
Published: November 2020

Background

The patients with implantable cardiac defibrillator (ICD) or cardiac resynchronization therapy device (CRT) have high risk of cardiac events, and lower physical activity has been thought to be associated with higher rate of cardiac events. On the other hand, cardiovascular implantable electronic devices can monitor physical activity through a built-in accelerometer. This study aimed to analyze long-term outcomes by device-based monitoring of physical activity in patients with ICD or CRT.

Methods

We retrospectively reviewed 89 patients with ICD/CRT, (56 males, 66.5 years old; ICD 45, CRT-D 42, CRT-P 2) who survived longer than 6 months after implantation in our institution. We analyzed physical activity by devices at 6th month and divided to 2 groups; In Low activity group (group L; n=38), their physical activity (moving time above 70 steps/min walk level) is less than 2 hours/day, and in Normal activity group (group N; n=51), physical activity is more than 2 hours/day. We evaluated their background characteristics in each group, physical activity at 12th month, and composite outcomes of hospitalization due to worsening of heart failure (HF) and death of any cause.

Results

Mean follow-up period was 57.4 months (median 40 months). In group L, they had higher age (71.1 y.o. vs. 63.2 y.o.; p=0.0003), higher rate of low EF (76.3% vs. 54.9%; p=0.035), and lower rate of attendance to outpatient cardiac rehabilitation program (10.5% vs 27.5%; p=0.043) compared with group N. 85.7% of patients in group L stayed in low physical activity at 12th month, and 87.8% of patient in group N stayed in normal physical activity. Composite outcomes of HF hospitalization and death occurred significantly higher in group L (Log-rank p<0.0001; 29.0% vs. 5.9% at 1 year, and 68.7% vs. 16.2% at 3 year: Figure 1) than in group N. Each event, HF hospitalization and death of any cause were shown significantly higher in group L (Log-rank p<0.0001). In group L, mortality rate of patients who could improve their physical activity from 6th month to 12th month was significantly lower than patients who stayed in low physical activity (Log-rank p=0.038).

Conclusions

Lower level of device-monitored physical activity was associated with higher mortality and higher rate of HF hospitalization in patients with ICD or CRT. Most of the patient in lower physical activity could not improve their activity from 6th month to 12th month. Early and continuous intervention is necessary especially for high risk patients such as high age or low EF.

Figure 1

Funding Acknowledgement

Type of funding source: None
Regular exercise after a diagnosis of atrial fibrillation and lower risks of cardiovascular disease: a nationwide population-based study
Authors: Ahn H.J , Lee S.R , Choi E.K , Han K.D , Jung J.H , Lim J.H , Yun J.P , Lee E.J , Cha M.J , Oh S , Lip G.Y.H
Published: November 2020

Introduction

There is a paucity of information about cardiovascular impacts related to the change of exercise habit after a new diagnosis of atrial fibrillation (AF). We aimed to investigate the influence of exercise on the risk of cardiovascular outcomes, such as ischemic stroke, heart failure (HF), and all-cause death, in patients with AF.

Methods

We included 66,692 patients with newly diagnosed AF (36.4% female, mean age 59.5 years, mean CHA2DS2-VASc 1.9) who underwent two serial health examinations before and after diagnosis of AF from 2010 to 2016, as provided by Korean National Health Insurance Corporation. The individuals self-reported a degree and frequency of exercise by questionnaires and doing vigorous physical activities ≥3 times/week or moderate physical activities ≥5 times/week was defined as a regular exercise group. The study population was divided into four categories according to the status of regular exercise before and after AF diagnosis: persistent non-exerciser (64.0%), new exerciser (13.4%), exercise drop-outs (12.5%), and exercise maintainer (10.1%). The primary outcomes were ischemic stroke, HF, and all-cause death during the follow-up.

Results

During a median 3.4 years follow-up, ischemic stroke, HF, and all-cause death occurred in 1905, 13112, and 2627 patients, respectively (incidence rates 8.5, 64.8, and 11.5 per 1,000 person-years, respectively). The change in exercise habits did not have a significant association with the risk of ischemic stroke (Figure 1). Regarding HF, those who newly initiated or maintained exercise after AF diagnosis showed a lower risk than those who do not exercise: hazard ratio, HR 0.93; 95% confidence interval, CI [0.88 to 0.98] and 0.90 [0.85 to 0.96] for each group, all p<0.001. Any experience of exercise involvement was associated with a lower risk of mortality than those without exercise: HR 0.76 [0.68–0.87] for new exerciser, 0.87 [0.78–0.98] for exercise drop-outs, and 0.62 [0.53–0.73] for exercise maintainer, all p<0.0001.

Conclusions

Patients who started or continued exercising after a new diagnosis of AF showed a lower risk of HF and mortality, but did not show an association with ischemic stroke. Regular exercise might improve the cardiovascular outcomes in patients with newly diagnosed AF.

Figure 1. CV impacts of exercise on AF patients

Funding Acknowledgement

Type of funding source: None
Association of C1q/TNF-related protein-9 (CTRP9) level with obstructive sleep apnea in patients with coronary artery disease
Authors: Wang X , Li Z , Du Y , Jia L , Fan J , Guo R , Ma X , Nie S , Wei Y
Published: November 2020

Background

Obstructive sleep apnea (OSA) is closely related to the incidence and progression of coronary artery disease (CAD), but the mechanisms linking OSA and CAD are unclear. C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that protects the heart against ischemic injury and ameliorates cardiac remodeling.

Purpose

We aimed to ascertain the clinical relevance of CTRP9 with OSA prevalence in patients with CAD.

Methods

From August 2016 to March 2019, consecutive eligible patients with CAD (n=154; angina pectoris, n=88; acute myocardial infarction [AMI], n=66) underwent cardiorespiratory polygraphy during hospitalization. OSA was defined as an apnea-hypopnea index (AHI) ≥15 events h–1. Plasma CTRP9 concentrations were measured by ELISA method.

Results

OSA was present in 89 patients (57.8%). CTRP9 levels were significantly decreased in the OSA group than in the non-OSA group (4.7 [4.1–5.2] ng/mL vs. 4.9 [4.4–6.0] ng/mL, P=0.003). The difference between groups was only observed in patients with AMI (3.0 [2.3–4.9] vs. 4.5 [3.2–7.9], P=0.009), but not in patients with AP (5.0 [4.7–5.3] ng/mL vs. 5.1 [4.7–5.9] ng/mL, P=0.571) (Figure 1). Correlation analysis showed that CTRP9 levels were negatively correlated with AHI (r=−0.238, P=0.003) and oxygen desaturation index (r=−0.234, P=0.004), and positively correlated with left ventricular ejection fraction (r=0.251, P=0.004) in all subjects. Multivariate analysis showed that male gender (OR 3.099, 95% CI 1.029–9.330, P=0.044), body mass index (OR 1.148, 95% CI 1.040–1.268, P=0.006), and CTRP9 levels (OR 0.726, 95% CI 0.592–0.890, P=0.002) were independently associated with the prevalence of OSA.

Conclusions

Plasma CTRP9 levels were independently related to the prevalence of OSA in patients with CAD, suggesting that CTRP9 might play a role in the pathogenesis of CAD exacerbated by OSA.

Figure 1. CTRP9 levels in OSA and non-OAS groups

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China
Blood pressure reduction following treatment with positive airway pressure in sleep apnea: data from the European Sleep Apnea Database
Authors: Svedmyr S , Grote L , Zou D , Bailly S , Lombardi C , Ludka O , Bonsignore M , Schiza S , Kvamme J.A , Basoglu O.K , Verbraecken J , Hedner J
Published: November 2020

Introduction

Positive airway pressure (PAP) treatment modifies blood pressure (BP) in patients with obstructive sleep apnea (OSA). We aimed to explore which factors that influence the BP response to PAP therapy in the European Sleep Apnea Database (ESADA).

Methods

A total of 2662 OSA patients with PAP therapy ≥90 days were included in the analysis (74% male, age 55±11 years, body mass index 32.3±6.1 kg/m2, 47% hypertensives, apnea-hypopnea index 40±24 events/h, treatment duration 1.0±1.1 years, PAP compliance 5.2±1.9 h/day). Anthropometric data, co-medications and office BP were assessed at baseline and follow-up visit.

Results

Systolic and diastolic BP were modestly reduced after PAP therapy compared to baseline (133±17 vs. 134±17 mmHg, 78±11 vs. 81±11 mmHg, p<0.001, respectively). In a generalized linear model controlling for anthropometric, PAP compliance and follow-up time, severe OSA at baseline (β [95% CI] −3.2 [−5.1 to −1.3], p=0.001), hypertension status (−2.0 [−3.3 to −0.7], p=0.003), weight reduction >2 kg at follow up (−2.0 [−3.7 to −0.4], p=0.016), and use of auto-adjusted PAP (−1.3 [−2.5 to −0.02], p=0.046) were associated with a reduction of systolic BP at follow-up.

Conclusions

BP reduction following PAP treatment in patients with moderate to severe OSA was modest. We identified several predictors of a favorable BP response including the use of auto adjusted PAP. Our findings suggest that weight reduction strategies in addition to PAP treatment should be considered to obtain adequate BP control in OSA patients.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): European Respiratory Society funded Clinical Research Collaboration (2015-2020)
Novel method of ASV titration for patient with severe heart failure. (Not for AHI improvement but for cardiac output)
Authors: Sekiguchi H , Tanaka Y , Tanino S , Suzuki M , Hagiwara N
Published: November 2020

Background

Adaptive servo-ventilation (ASV) is reportedly beneficial for the treatment of heart failure in patients with central sleep apnea syndrome. However, the recent SERVE-HF trial reported that ASV treatment increased mortality in these patients. One cause of the negative result was considered to be the low output induced by high expiratory positive airway pressure (EPAP) against the background of low left ventricular ejection fraction (LVEF).

Hypothesis

We hypothesized that optimized ASV settings can be determined by evaluating outflow by using echocardiography, thereby ensuring benefits for patients with severe heart failure (HF).

Methods

Between July 2016 and March 2017, we optimized ASV settings by using hemodynamic parameters on echocardiography in hospitalized patients with severe HF treated with catecholamine or who were candidates for heart transplantation. We calculated stroke volume (SV) by using the time-velocity integral in the left ventricular outflow tract and compared the response to ASV with EPAP settings of 2, 4, 6, or 8 mmHg. We determined the optimal setting at which the SV reached the maximum value and compared this with the settings at baseline and discharge. We also compared rehospitalization and all-cause mortality between the patients who used ASV with titration (n=28) and without titration (n=37).

Result

We evaluated 28 patients with severe HF (mean EF, 32%). ASV treatment improved the SV (from 53.4 to 58.8 ml, P<0.05) when optimal settings were used. However, the SV decreased when ASV was performed with a higher-than-optimal EPAP setting. Moreover, at discharge, the EPAP setting was lower than at baseline (mean EPAP, 4.75 cmH2O decreased to 3.71 cmH2O, P<0.05). During the follow-up (median, 420 days), more hospitalizations and deaths occurred in the patients without ASV titration (48.8% vs 37.8%) than in those with ASV titration (28.6% vs 21.4%, respectively; Figure 1).

Conclusion

In patients with severe HF, high EPAP decreased the SV and optimal settings were different at baseline and after treatment. The result indicated that the optimal setting for ASV may be beneficial for preventing rehospitalization and death. Whether optimal ASV settings reduce mortality in these patients must be investigated.

Figure 1

Funding Acknowledgement

Type of funding source: None
Markers of subclinical cardiac disease associate with thresholds for pre-diabetes and diabetes in the general population: data from the ACE 1950 Study
Authors: Myhre P , Lyngbakken M , Berge T , Roysland R , Aagaard E , Kvisvik B , Norseth J , Pervez O , Tveit A , Steine K , Omland T , Rosjo H
Published: November 2020

Background

Diabetes mellitus (DM) is associated with increased risk of left ventricular (LV) remodeling and incident heart failure. However, the associations between dysglycemia and subclinical cardiac disease in middle-aged subjects recruited from the general population are not established.

Purpose

To assess the associations of dysglycemia and diagnostic DM thresholds with indices of subclinical cardiac injury and dysfunction in the general population.

Methods

We included participants born in 1950 from the Akershus Cardiac Examination 1950 Study with available biomarker measurements (n=3,688). We used regression models and restricted cubic splines (knots selected from lowest Akaike Information Criterion) to assess the association between glycated hemoglobin A1c (HbA1c) and cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), and echocardiographic parameters. We classified participants with self-reported diagnosis of DM or HbA1c ≥6.5% (48 mmol/L) as DM, participants with HbA1c 5.7–6.5% as pre-DM, and participants with HbA1c <5.7% (39 mmol/mol) as no-DM.

Results

Mean age was 63.9±0.7 years, mean body mass index (BMI) 27.2±4.4 kg/m2, and 1,795 participants (49%) were women. DM was classified in 380 participants (10%), pre-DM in 1,630 participants (44%) and no-DM in 1,678 participants (46%). Increasing HbA1c concentrations were associated with younger age, male sex, obesity, hypercholesterolemia, hypertension, and established coronary artery disease in adjusted analyses. In models adjusted for age, sex, BMI, smoking, hypertension, atrial fibrillation, coronary artery disease and renal function, greater HbA1c was associated with increasing logcTnT and logCRP concentrations, decreasing logNT-proBNP concentrations and worse global longitudinal strain and E/e' (p<0.001 for all). LV mass index was not associated with HbA1c in adjusted models (p=0.23). All five associations were non-linear in the total study population (p<0.001 for non-linearity for all) with robust, linear associations in the pre-DM range of HbA1c, also in adjusted models, and attenuated associations in the no-DM and DM range (Figure 1).

Conclusion

We found robust, linear associations between HbA1c and indices of subclinical cardiac injury and dysfunction among participants classified as pre-DM, while associations were more attenuated among participants with DM. Preventive measures for cardiovascular disease should be considered also in patients with dysglycemia and HbA1c below the established cutoff for DM.

Figure 1. P-values for overall trend

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Akserhus University Hospital
Clinical phenotypes of atrial fibrillation and risk of mortality: a cluster analysis
Authors: Pastori D , Antonucci E , Milanese A , Violi F , Pignatelli P , Palareti G , Farcomeni A
Published: November 2020

Background

Patients with atrial fibrillation (AF) experience a high mortality rate despite optimal antithrombotic treatment. Characteristics of AF patients at higher mortality risk have been barely described so far and no risk score has been specifically developed at this aim. Furthermore, a clinical approach based on risk scores present some limits such as to not consider some important risk factors for mortality, and many available scores have poor predictive value. Cluster analysis may play a role in overcoming limitations of risk scores, especially in the case of overlapping risk factors.

Purpose

To identify of clinical phenotypes by using an unbiased statistical approach, such as the cluster analysis.

Methods

Cluster analysis was used to identify clinical phenotypes of AF patients associated with all-cause mortality in 5,171 AF patients from the START registry. Clinical variables used for the analysis were age, sex, diabetes, previous cerebrovascular events, previous cardiovascular events, heart failure, peripheral artery disease, use of non-vitamin K oral anticoagulants, cancer, pulmonary disease, smoking habit, previous major bleeding. The risk of all-cause mortality in each cluster was analyzed.

Results

We identified 4 clusters (Figure 1). Cluster 1 was composed by youngest patients, with obesity and paroxysmal AF; Cluster 2 by patients with low cardiovascular risk factors and high proportion of cancer; Cluster 3 by men with diabetes and coronary and peripheral artery disease, a high proportion of thrombocytopenia, and a high use of aspirin, proton pump inhibitors, and statins; Cluster 4 included the oldest patients, mainly women, with previous cerebrovascular disease, persistent/ permanent AF, heart failure, kidney disease and anemia. In this cluster there was the highest use of digoxin and NOACs.

During 9856,84 patient/years of observation, 386 deaths (3.92%/year) occurred. Mortality rates significantly increased across clusters: 0.42%/year (cluster 1, reference group), 2.12%/year (cluster 2, adjusted hazard ratio [aHR] 3.306, 95% confidence interval [CI] 1.204–9.077, p=0.020), 4.41%/year (cluster 3, aHR 6.702, 95% CI 2.433–18.461, p<0.001) and 8.71%/year (cluster 4, aHR 8.927, 95% CI 3.238–24.605, p<0.001).

Conclusions

We identified different clinical phenotypes of AF patients by cluster analysis which were specifically associated with mortality. This approach may help identify patients at higher risk of mortality.

Figure 1

Funding Acknowledgement

Type of funding source: None
Benefit of high cardiovascular health for incident cardiovascular events and mortality in elderly population
Authors: Joung B , Yang P.S , Sung J.H , Jang E.S , Yu H.T , Kim T.H , Uhm J.S , Kim J.Y , Pak H.N , Lee M.H
Published: November 2020

Background

There is consistent evidence of the association between ideal cardiovascular health and lower incident cardiovascular disease (CVD); however, most studies used a single measure of cardiovascular health.

Purpose

To examine the association of change in cardiovascular health with subsequent incident CVD and mortality in elderly population.

Methods

In the Korea National Health Insurance Service-Senior (≥60 years) cohort, 312,736 participants who received national health check-ups between 2005–2012 were assessed for eligibility. Using the 7metrics of the American Heart Association (nonsmoking; and ideal levels of body mass index, physical activity, diet, blood pressure, fasting blood glucose, and total cholesterol), participants with 0 to 2, 3 to 4, and 5 to 7 ideal metrics were categorized as having low, moderate, and high cardiovascular health. Change in cardiovascular health over 2 years between 2005 and 2006 was considered.

Results

The study population included 162,149 participants without prior CVD or malignancy (median age at baseline, 69 [IQR 66–73] years; 91,408 [56.2%] women), of whom 59,887 had data about cardiovascular health change. Over a median follow-up of 5.8 (5.5–8.0) years, 5346 incident CVD events and 6035 death occurred. In multivariable analysis and compared with individuals with persistently low cardiovascular health (consistently low group, 7.9% of participants; CVD incident rate per 1000 person-years, 21.1 [95% CI, 19.4–23.0]), a lower CVD risk was observed in the consistently moderate group (38.7% of participants; absolute rate difference per 1000 person-years, −4.8 [95% CI, −5.5 to −4.1]; HR, 0.77 [95% CI, 0.70–0.85]), the moderate to high group (11.6% of participants; absolute rate difference per 1000 person-years, −7.7 [95% CI, −8.8 to −5.5]; HR, 0.62 [95% CI, 0.55–0.70]), the high to moderate group (11.2% of participants; absolute rate difference per 1000 person-years, −7.2 [95% CI, −8.3 to −5.9]; HR, 0.64 [95% CI, 0.56–0.72]), and the consistently high group (11.3% of participants; absolute rate difference per 1000 person-years, −10.2 [95% CI, −11.2 to −9.1]; HR, 0.51 [95% CI, 0.44–0.58]). A lower mortality risk was observed in the consistently moderate group, the moderate to high group, and the high to moderate or high groups.

Conclusion

Among a group of elderly participants without CVD, there was benefit of moderate or high cardiovascular health for incident cardiovascular events and mortality.

Funding Acknowledgement

Type of funding source: None
Updated treatment thresholds in the 2019 ESC/EAS dyslipidaemia guidelines substantially expand indications for statin use for primary prevention at population level: results from the Rotterdam Study
Authors: Pavlovic J , Kavousi M , Ikram M.A , Leening J.G
Published: November 2020

Background

In the recent update of the ESC/EAS practice guidelines for the management of dyslipidaemias, indications for statin treatment in primary prevention have been expanded to those at lower cardiovascular disease (CVD) risk and with lower LDL levels, as well as to those 65 to 75 years of age according to their level of predicted CVD risk.

Purpose

To compare the implications of the 2016 and 2019 ESC/EAS guidelines and determine the extent to which these updates affect treatment recommendations at population level.

Methods

We calculated 10-year CVD risk following the 2016 and 2019 ESC/EAS guideline recommendations and proportions of individuals qualifying for statin treatment categories per guideline. The study population included 7262 participants free of CVD, aged 45 to 75 years, from the Dutch prospective population-based Rotterdam Study.

Results

Mean (SD) age was 61.1 (6.9) years and 58.2% were women. Diabetes was present in 8.4% of the participants, 24.7% were smokers, mean LDL was 3.7 (0.9) mmol/L, and mean blood pressure was 137/80 (20/11) mmHg. Next to lifestyle changes, the 2016 and 2019 ESC/EAS guidelines recommend statin treatment in 13.2% (N=961) and 37.7% (N=2738) of the total population and consider statin treatment in 37.0% (N=2689) and 51.4% (N=3733), respectively. When stratified by 5-year age groups, the 2016 and 2019 ESC/EAS guidelines overall suggest a respective 29.7% (N=411) and 60.7% (N=839) of adults aged 45–55 years to be considered for statin treatment. While adults with an estimated 10-year SCORE risk of fatal CVD <1% and LDL <4.9 mmol/L were deemed to be at sufficiently low risk in the 2016 ESC/EAS guidelines and hence were suggested only lifestyle advice to modify their cardiovascular risk, in the 2019 update, 517 individuals (i.e. 37.4% of 1383 adults aged 45–55 years) were considered for statin treatment. The 2016 ESC/EAS guidelines did not provide treatment recommendations for individuals aged >65 years, while the 2019 ESC/EAS guidelines recommend statin treatment in 69.2% (N=1430) and considers treatment in another 27.7% (N=571) among the study population aged 65–75 years (N=2065).

Conclusions

Updated treatment recommendations in the 2019 ESC/EAS dyslipidaemia guideline substantially expand statin treatment to asymptomatic individuals aged 45–55 at low risk, and individuals aged 65–75 years. Whether the broadening of statin indications in asymptomatic low-risk individuals and those aged 65–75 years will lead to greater uptake of primary prevention efforts and thereby long-term lowering of the burden of CVD in Europe, remains to be investigated.

Funding Acknowledgement

Type of funding source: None
The role of lipopolisaccharide and antibodies to the lipopolysaccharide in the systemic circulation to the cardiovascular risk group determination
Authors: Pokusaeva D
Published: November 2020

The inflammatory concept of atherogenesis is the leading one. Its finds development in the endotoxin theory of atherosclerosis, confirmed by numerous experimental studies and a several of clinical observations. But the involvement of lipopolysaccharide (LPS) in atherogenesis in humans has been studied without assessing the morphological changes in the structure of the vascular wall and not included an antibodies response. Existing scales for assessing the risk of developing cardiovascular diseases have a maximum error for patients with an average level risk. We examined 113 patients belonging to one group of cardiovascular risk (<5% on the SCORE scale). We evaluated such indicators, which can be attribution to risk factors and can be application in practice, as the level of LPS in blood plasma, the level of antibodies to the LPS Salmonella minnnesota RE 595 (AB-LPS-1) and LPS Escherichia coli O55 (AB-LPS-2) in serum. A duplex scanning of extracranial brachiocephalic arteries (BCA) and a testing for lipid profile were made. It was revealed that the lipid profile do not allow to evaluate the condition of the BCA wall prior duplex scanning. A significant difference was found in the concentration and frequency of occurrence of LPS and AB-LPS indicators among patients with varying degrees of severity of atherosclerotic lesions of BCA (table). Thus, the inclusion of as risk factors the level of LPS, the concentration of AB-LPS can help in predicting the condition of the carotid arteries wall and, accordingly, in changing the degree of risk in patients at the primary diagnosis level without the participation of high-tech expensive imaging techniques. Simple binary models with high specificity and sensitivity were constructed using cluster analysis to predict the severity of BCA atherosclerosis using concentration of LPS and AB-LPS adapted for practical (figure).

Comparison risk factors between groups Parameter Group (by arterial wall state) p-value Intact wall Thickening of TIM ASP Cholesterol, mmol/L 6.43 [6.04; 6.82] 5.81 [4.75; 8.28] 6.63 [5.68; 7.51] 0.2750 LDL, mmol/L 4.43 [4.03; 4.78] 3.64 [3.04; 4.98] 4.74 [3.74; 5.28] 0.0558 HDL, mmol/L 1.09 [0.94; 1.29] 1.21 [1.07; 1.51] 1.13 [0.98; 1.35] 0.3198 Triglycerides, mmol/L 1.72 [1.23; 2.54] 1.21 [0.91; 1.92] 1.48 [0.99; 2.07] 0.2752 Atherogenicity index 4.23 [3.45; 6.32] 3.67 [2.91; 4.48] 4.93 [3.92; 5.68] 0.3532 LPS, EU/ml 0.90 [0.60; 1.52] 0.60 [0.41; 0.98]* 1.20 [0.60; 1.8]* 0.0067* AB-LPS-1, c.o.u.d. 216.0 [132.5; 248.5]* 127.5 [105.75; 221.5] 123.0 [91.00; 187.0]* 0.0444* AB-LPS-2, c.o.u.d. 374.0 [199.0; 481.0] 399.5 [195.75; 451.0] 265.0 [200.0; 399.0] 0.1991 *Result was significant at p<0.05 at post-hoc pairwise comparisons.

“Decision tree” for a group of patients

Funding Acknowledgement

Type of funding source: None
Risk factor management in coronary patients: results from the EUROASPIRE V survey
Authors: Vynckier P , Gevaert S , Kotseva K , Tokgozoglu L , De Bacquer D , De Smedt D
Published: November 2020

Background

Previously, there has been a misperception that cardiovascular disease (CVD) mainly affects males. Although lately, there is increasing awareness about the risk of CVD in women, evidence suggests that the management of women with CVD is suboptimal.

Purpose

The aim of this study is to look at gender differences in treatment and risk factor control after a coronary event across countries with varying income levels.

Methods

Analyses were based on the ESC-EORP EUROASPIRE V survey, including patient information from 27 European countries. Patients included (18–80 years), were hospitalised for an ischaemic coronary event. Information on medical treatment, risk factors and behavioural changes were obtained during patient interviews (6 months to 2 years after hospitalization). Findings on treatment and risk factor control were compared with the European guidelines on CVD prevention (2016). Country classification by income level (low/medium income vs. high income) was done according to the World Bank Atlas method. Logistic regression analyses adjusted for sex, age, education level, country income, surgical intervention, stroke, heart failure and diabetes were performed.

Results

Data from 8261 coronary patients, of which 25.8% women, were included in the analyses. Mean (SD) age at the interview was 62.95 (9.72) years for men and 65.36 (9.21) years for women. First, when looking at the evidence based medication intake, no gender differences were seen in the prescription of antiplatelets/aspirin, whereas statins were more often prescribed in men (82.8% vs. 77.7%; p=0.002). A closer look by country income revealed that this difference is entirely due to the higher statin use among men from low/medium income countries (79.6% vs. 72.3%; p=0.004). Second, the risk factor profile differed substantially between genders. Overall, a worse risk factor profile was seen in women. Although, men were more likely to smoke (20.7% vs. 12.8%; p<0.001), women were less physically active (63.2% vs. 72.5%; p<0.001), had more obesity (34.9% vs. 45.7%; p<0.001) and central obesity (51.8% vs. 78.0%; p<0.001), and had a worse lipid control (65.9% vs. 74.3%; p<0.001). Overall, no gender differences were seen in diabetes prevalence and blood pressure control. A closer look at country income level showed that the gender difference in smoking prevalence dissolved in high income countries. In addition, women in low income countries were more likely to suffer from diabetes (26.7% vs. 38.9%; p<0.001).

Conclusion

These findings suggest a worse risk factor profile in women despite little to no gender differences in medical treatment. Further research is needed to understand the gender-differential in risk factor control.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Fonds voor hartchirurgie - Fonds pour la Chirurgie Cardiaque
Prognostic impact of cascade screening for familial hypercholesterolemia on cardiovascular events
Authors: Tada H , Okada H , Nomura A , Nohara A , Yamagishi M , Takamura M , Kawashiri M
Published: November 2020

Background

Early diagnosis and timely treatment for the patients with familial hypercholesterolemia (FH) can substantially lower the risk of atherosclerotic cardiovascular disease (ASCVD). In this sense, cascade screening could be one of the most useful options. However, few data exist regarding the impact of cascade screening for FH on the reduction of risk of ASCVD events.

Objectives

We aimed to evaluate the prognostic impact of cascade screening for FH.

Methods

We retrospectively investigated the health records of 1,050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiovascular events (MACE). The median period of follow-up was 12.3 years (interquartile range [IQR] = 9.1–17.5 years), and MACE included death from any causes or hospitalization due to ASCVD events.

Results

During the observation period, 246 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr, P<0.001), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.36; 95% CI = 0.22 to 0.60; P<0.001) when compared with the probands, even after adjusting for those known risk factors.

Conclusions

The identification of patients with FH via cascade screening appeared to result in better prognoses.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Scientific research grants from the Ministry of Education, Science and Culture of Japan (no. 16K19394, 18K08064, and 19K08575)