bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of future atherosclerosis in 13 years from young asymptomatic adults
Authors: Huynh Q , Magnussen C , Venn A , Dwyer T , Marwick T 
Published: October 2021

Abstract

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

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

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

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

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

Abstract

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

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

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

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

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

Abstract

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

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

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

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

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

Abstract

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

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

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

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

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

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

Abstract

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

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

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

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

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

Abstract

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

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

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

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

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

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

Abstract

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

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

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

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

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

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

Abstract

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

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

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

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

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

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

Abstract

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

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

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

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

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

Funding Acknowledgement
Type of funding sources: None.