bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal associations of cumulative dyslipidaemia from mid-adolescence through young adulthood with arterial stiffness progression: the ALSPAC study
Authors: Agbaje A O , Lloyd-Jones D M , Magnussen C G , Tuomainen T P 
Published: October 2022

Abstract

Background
Arterial stiffness assessed with carotid-femoral pulse wave velocity (cfPWV) strongly predicts the risk of cardiovascular morbidity and mortality. Recent temporal causal evidence suggests that cfPWV progression may precede the development of cardiometabolic diseases in adolescence, young adults, and middle-aged adults. However, the longitudinal relationship between cfPWV progression and dyslipidaemia in the young population is unclear.

Purpose
To investigate the longitudinal associations of total cholesterol (TC), non–high-density lipoprotein cholesterol (non–HDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and low-density lipoprotein cholesterol (LDL-C) with cfPWV progression in adolescents.

Methods
We studied 1779 British 15-year-olds (50% females) followed up for 9 years. TC, triglyceride, and HDL-C were measured in line with standard protocols at ages 15, 17, and 24 years, respectively. LDL-C and non-HDL-C were estimated. Lipid phenotypes were categorized based on the 2011 National Heart, Lung, and Blood Institute classification into normal (reference), and elevated/dyslipidaemia. At age 17 and 24 years, cfPWV was computed from pressure waveforms obtained using the Vicorder device. We conducted linear mixed-effect model analyses and adjusted for sex, age, high sensitivity C-reactive protein, glucose, insulin, total fat mass, lean mass, heart rate, systolic blood pressure, diastolic blood pressure, sedentary time, light physical activity, moderate to vigorous physical activity, family history of cardiometabolic disease, socioeconomic status, pubertal attainment, and smoking status, in addition to lipid covariates such as HDL-C, LDL-C, or triglyceride depending on the predictor. However, TC and non-HDL-C analyses were not adjusted for lipids.

Results
Participants' mean (SD) age in years at different time points were 15.43 (0.29), 17.69 (0.31), and 24.53 (0.72). Persistently elevated/dyslipidaemia TC: effect estimate 0.006 m/s [95% CI −0.023 to 0.035; p=0.683], non–HDL-C: 0.004 m/s [−0.025 to 0.033; p=0.771], LDL-C: 0.017 m/s [−0.019 to 0.052; p=0.351], and Triglyceride: −0.009 m/s [−0.036 to 0.018; p=0.532] from 15 through 24 years were not cumulatively associated with the 7-year cfPWV progression. Persistent borderline-low/very-low HDL-C: 0.007 m/s [−0.017 to 0.031; p=0.556] was not associated with cfPWV progression.

Conclusion
These findings suggest that elevated lipids and dyslipidaemia from mid-adolescence through young adulthood were not associated with arterial stiffness progression, a marker of preclinical arteriosclerosis. Thus, lipid-lowering interventions targeted at preventing or reversing arterial stiffness progression in the young may be ineffective, particularly in a healthy young population.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Finnish Cultural Foundation
Evaluation of the effects of immunization against PCSK9 on selected microRNAs involved in cholesterol homeostasis
Authors: Ataei S , Ganjali S , Banach M , Sahebkar A 
Published: October 2022

Abstract

Background
MicroRNAs (miRNAs) have been discovered as novel modulators of gene expression. These molecules are involved in regulating lipid metabolism through a complicated interactive mechanism involving gene regulatory networks and can play a role in metabolic diseases. PCSK9 (proprotein convertase subtilisin/Kexin 9) is a critical regulator in cholesterol homeostasis. PCSK9 inhibition is an effective therapeutic strategy for the treatment of dyslipidemia. Accordingly, it is essential to identify the controlling mechanisms of the PCSK9 and the effects of its inhibitors on microRNAs involved in cholesterol homeostasis.

Purpose
Considering the role that miR-27a, miR-30c, and miR-191 play in regulating genes involved in cholesterol homeostasis, we investigated the effect of immunization against PCSK9 on the mentioned miRNAs.

Methods
A PCSK9 immunogenic peptide constructed by linking a short PCSK9 mimotope peptide to a tetanus peptide was used for immunization. The PCSK9 immunogenic peptide construct was mixed homogeneously with 0.4% alum adjuvant at a ratio of 1:1 for use as vaccine formulation. Mice in the vaccinated group were inoculated subcutaneously in four terms with bi-weekly intervals. In order to assess the expression of miRNAs in vaccinated mice' livers, sampling was carried out two weeks after the last injection. The levels of miR-27a, miR-30c, and miR-191 expression in the liver of vaccinated mice were evaluated using real-time quantitative PCR, and relative expression levels were presented as fold change normalized to U6 as the internal control.

Results
Hepatic miR-27a expression was significantly decreased in vaccinated mice compared with the control mice (fold change: 0.731±0.1, p=0.027). There was a borderline nonsignificant reduction in the hepatic expression of miR-30c in the vaccine group compared to the control group (fold change: 0.569±0.1, p=0.078). No significant difference was detected in the hepatic expression of miR-191 between the vaccine and control groups (fold change: 0.852±0.1, p=0.343).

Conclusions
Immunization against PCSK9 leads to decreased hepatic expression of miR-27a. Since miR-27a is involved in the regulation of targets like angiopoietin-like 3 and glycerol-3-phosphate acyltransferase 1, its reduction may explain part of the lipid-lowering activity of PCSK9 vaccine.

Funding Acknowledgement
Type of funding sources: None.
Realistic approach to evaluate the effect of baseline lipid profile in post cardiac surgery: Restricted Cubic Spline model
Authors: Sheikhy A , Fallahzadeh A S , Fallahzadeh A , Hosseini K , Hosseini K 
Published: October 2022

Abstract

Background
There are still many uncertainties in the association between lipid profile and post coronary artery bypass grafting (CABG) outcomes. Although simplifying the association to linear equations makes it understandable but cannot explain many findings.

Methods
Total 17,555 patients who underwent isolated CABG between 2014 and 2016 were evaluated. During the median follow-up of 75.24 months the Restricted Cubic Splines (RCS) estimated from the Cox regression model adjusted for all possible confounders was applied to show a nonlinear relationship of lipid profile contents with the “ln hazard ratio” of mortality and major cerebro-cardiac events.

Results
The relationship between LDL-C and HDL-C with all-cause mortality were non-linear (non-linear P were 0.004 and &lt;0.001, respectively). The relationship between remnant cholesterol and all-cause mortality was linear (linearity P=0.023). Among men, those in the highest LDL-C level (Q4, LDL-C &gt;114) and those in the lowest HDL-C level (Q1, HDL-C &lt;30) showed a significantly higher risk of all-cause mortality compared to other groups (compared with Q3, LDL-C Q4, HR=1.16, 95% CI: 1.02–1.26, P=0.014; HDL-C Q1, HR=1.14, 95% CI: 1.01–1.31, P=0.041). Female patients in the lowest HDL-C level (Q1, HDL-C &lt;30) showed a significantly higher (compared with Q3, HR=1.14, 95% CI: 1.01–1.31, P=0.028) and those in the highest HDL-C level (Q4, HDL-C &gt;43) showed a significantly lower (compared with Q3, HR=0.74, 95% CI: 0.58–0.98, P=0.019) risk of all-cause mortality.

Conclusion
Determining a universal cut off for components of lipid profile may be misleading and should better be revised. Extreme values (very low or very high) for HDL-C and LDL-C have different effects on cardiovascular outcomes.

Funding Acknowledgement
Type of funding sources: None.
Comparison over 25 years of the burden of familial hypercholesterolemia on hospitalizations for coronary heart disease in a French-Canadian founder population
Authors: Lauziere A , Brisson D , Tremblay G , Bedard S , Khoury E , Gaudet D 
Published: October 2022

Abstract

Background
Over the last 25 years, effective treatments, such as potent statins, ezetimibe and PCSK9 inhibitors have gradually emerged to treat heterozygous familial hypercholesterolemia (FH) and guidelines have been progressively developed internationally to promote FH health surveillance, early diagnosis and optimal clinical management. However, the impact of these measures on the burden of FH is not well documented. Although recent genetic and epidemiological studies suggest that the prevalence of familial hypercholesterolaemia (FH) is approximately twice than initialy expected (1:250) (1), it remains significantly higher among French Canadians (FC) (2,3).

Purpose
To compare over 25 years the management and burden of FH among patients hospitalized for an acute coronary heart disease (CHD) event in a FC founder population with a high prevalence of FH.

Methods
Lipid profiles, cardiovascular risk factors, lipid management and FH status of 2,029 FC patients consecutively hospitalized for an acute CHD event between 2017 and 2022 (2022 Cohort) were compared to those of 2,506 patients with angiographically-confirmed CHD who were admitted between 1995 and 1998 (1998 Cohort) (4). FH status was based on molecular, Simon Broome or FH Canada (5) criteria. Statistical comparisons were made using Chi-square and Student's t-tests for independent samples.

Results
Over a 25-year interval, most patients hospitalized for CHD were men (74.5% in 1998 vs 73.4% in 2022). At the time of admission, 23.0% of CHD patients had LDL-Cholesterol levels &gt;5.0 mmol/L in 1998 compared to 1.3% in 2022 (p&lt;0.001). FH was diagnosed in 9.6% of patients in the 1998 cohort compared to 5.5% in 2022 (p&lt;0.001). Overall, the prevalence of obesity, type 2 diabetes and uncontrolled hypertension tended to be higher in 1998, including in FH (p&lt;0.05). The proportion of FH patients hospitalized for CHD who were treated with a statin or a combination of lipid-lowering agents at the moment of admission was 28.4% in 1998 compared to 61.2% in 2022 (p&lt;0.001). FH patients hospitalized for CHD were significantly older in 2022 than in 1998 (59.03±11.17 vs 50.14±11.32 years; p&lt;0.001). Accordingly, the prevalence of premature CHD requiring an hospitalization significantly decreased from 1998 to 2022 in FH (64.3% vs. 44.1%, p&lt;0.001).

Conclusions
Over a 25-year period, FH patients hospitalized for CHD tend to be older and contribute to a lower proportion of hospitalizations. Despite significant improvement in treatment, FH diagnosis and management remain sub-optimal, even in a founder population where FH represents a significant population burden.

Funding Acknowledgement
Type of funding sources: None.
Correlation of lipoprotein(a) with parameters of lipid profile and other cardiovascular risk factors in patients with familial combined hyperlipidemia
Authors: Andrikou I , Dima I , Lazarou E , Grigoriou K , Skoumas I , Tsioufis K , Vlachopoulos C 
Published: October 2022

Abstract

Background
According to previous studies, Familial Combined Hyperlipidemia (FCH) is related to metabolic syndrome. However, it is unclear whether the presence of increased Lipoprotein (a) [Lp (a)] modifies the characteristics of metabolic syndrome in patients with FCH. Thus, the aim of our study was to identify and compare the components of metabolic syndrome in patients with FCH according to their Lp (a) levels.

Methods
We enrolled 906 patients (592 males, mean age 49±11 years) who fulfilled the FCH criteria, from the outpatient lipid clinic of our hospital.Venous blood samples were obtained for the determination of plasma glucose and lipid profile [i.e., total cholesterol, triglycerides (TG), low and high-lipoprotein cholesterol, (LDL, HDL)], as well as levels of Lp (a). Moreover, information was obtained regarding demographic characteristics and blood pressure (BP) levels. Diagnosis of hypertension was based on BP levels≥140/90 mmHg and metabolic syndrome was defined according to ATP III criteria.

Results
In the total population of 906 patients with FCH, 58% (n=524) had metabolic syndrome. We identified a negative correlation between levels of Lp (a) and TG (r=−0.07, p=0.03) and a positive correlation between levels of Lp (a) and HDL (r=0.08, p=0.02). Also, there was a trend towards a negative correlation between levels of Lp (a) and waist circumference (r=−0.6, p=0.06). Moreover, the group of patients with increased Lp (a) levels (≥30mg/dl, n=289, 32%) compared to those with low Lp (a) levels (&lt;30mg/dl, n=616, 68%)had hypertension in a greater percentage (44% vs 36%, p=0.02), lower levels of TG (278±146 vs 302±172 mg/dl, p=0.04), higher levels of HDL (42±11 vs 39±9 mg/dl, p=0.01) and increased levels of LDL (193±55 vs 185±53 mg/dl, p=0.05), while there was no difference in glucose levels (104±24 vs 102±20 mg/dl, p=0.18). In multiple logistic regression analysis increased Lp (a) levels were independent determinants of lower triglycerides levels (&lt;150mg/dl) (OR 0.59, 95% CI 0.36–0.95), after adjustment for confounding factors.

Conclusions
In patients with FCH, increased Lp (a) is related to lower levels of triglycerides, higher levels of HDL, lower waist circumference levels and increased prevalence of hypertension. Thus, it seems that Lp (a) differentiates the expression of metabolic syndrome characteristics in patients with Familial Combined Hyperlipidemia.

Funding Acknowledgement
Type of funding sources: None.
Lipoprotein (a) and new-onset type-2 diabetes in patients with familial combined hyperlipidemia: a 9 years follow-up study
Authors: Andrikou I , Dima I , Grigoriou K , Lazarou E , Skoumas I , Tsioufis K , Vlachopoulos C 
Published: October 2022

Abstract

Background
Elevated lipoprotein(a) [Lp(a)] levels have been related with increased cardiovascular (CV) risk in the general population. However, its relationship with type-2 diabetes and CV risk in patients with Familial Combined Hyperlipidemia (FCH) is rather unclear. Thus, the aim of our study was to investigate the prognostic role of Lp(a) regarding new-onset type-2 diabetes and major adverse cardiovascular outcomes in patients with FCH.

Methods
485 patients from the outpatient lipid clinic of our hospital (301 males,mean age 49.8±10.8 years, 35%smokers, 16% with diabetes mellitus), without history of CV disease, who fulfilled the FCH criteria participated in the study. Participants were evaluated for a mean follow-up period of 8.9±7.5 years with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of plasma glucose, lipid profile, and levels of Lp(a). All subjects were on lipid-lowering medication (statin and ezetimibe or fibrate) during the follow-up period. The endpoints of our study was new-onset diabetes and the composite of major CV events (coronary artery disease events and stroke).

Results
The incidence of new-onset diabetes during the follow-up period was 10% (n=42). The group of patients with new-onset diabetes (n=42) had lower levels of Lp(a) at baseline compared to those without new-onset diabetes (n=376) (23.8±19.2 vs 32.9±39.5 mg/dl, p=0.01). Also, those with new-onset diabetes had a lower percentage of increased Lp(a) levels (≥30 mg/dl) at baseline compared to those without new-onset diabetes (21% vs 34%). Multiple Cox regression analysis revealed that increased Lp(a) (≥30 mg/dl) is an independent predictor of lower diabetes incidence during the follow-up period (HR 0.39, 95% CI 0.17–0.90), after adjustment for confounding factors. Moreover, the incidence of new-onset CV events in the total population was 6.4% (n=31).In the group of patients with increased Lp(a) levels at baseline (≥30 mg/dl, n=159, 33%) there was a trend towards a greater incidence of CV events during the follow-up period, compared to the group of patients with lower Lp(a) levels (&lt;30 mg/dl, n=326, 67%), although the difference between the two groups was not statistically significant (8.8% vs 5.1%, p=0.1).

Conclusions
In patients with FCH, increased baseline Lp(a) is an independent predictor of lower incidence of new-onset type-2 diabetes after an almost 9 years follow-up period. Moreover, increased Lp(a) seems to convey an increased CV risk also in patients with FCH.

Funding Acknowledgement
Type of funding sources: None.
Comparison of severe hypercholesterolemia patients with and without pathogenic variants
Authors: Nanchen D , Von Kanel T , Ehret G , Brun N , Sudano I , Rodondi N , Rickli H , Girod G , Ballhausen D , Falciano R , Beer J H , Gallino A 
Published: October 2022

Abstract

Introduction
A pathogenic variant causally related to familial hypercholesterolemia (FH) is found in less than half of adults with severe hypercholesterolemia. The characteristics of adults with severe hypercholesterolemia without pathogenic variant have been poorly described, and it remains unclear whether intensive preventive strategies should be recommended. In this study we compared the characteristics of adults with severe hypercholesterolemia with and without pathogenic variant for FH.

Methods
Between November 2020 and February 2022, we recruited individuals older than 16 years with a Dutch Lipid Clinic Network (DLCN) score ≥6 and genotyped LDLR, APOB and PCSK9. Participants were part of the multicenter CATCH study, testing the implementation of genetic cascade screening for FH in Switzerland. All genetic analyses were performed in a single central laboratory. Variants classified as likely pathogenic or pathogenic were interpreted as FH-causing. We also assessed socio-economic status, cardiovascular risk factors, lifestyle behavior, and use of lipid-lowering drugs.

Results
In total, 150 non-related adults with a DLCN score of ≥6 were included, out of whom 62 (41.3%) had genetically confirmed FH. Most variants were found in the LDLR gene (77%). Overall, 70% were using a lipid-lowering drug and 20% were current smokers. Compared to adults with genetically confirmed FH, those without pathogenic variants were older (57.6 vs 50.4 years old), had lower untreated LDL-cholesterol levels (p&lt;0.001), higher triglyceride levels (p=0.032), higher BMI (p=0.014), and had more frequently hypertension (62.5% vs 36.1%). No socio-economic differences were observed. Although adherence to Mediterranean diet was higher among adults without pathogenic variant, they reached less frequently the recommended level of physical activity than adults with genetically confirmed FH (66.2% vs 82.1%). Xanthomas or xanthelasmas, but not corneal arcus, were more frequent among genetically confirmed FH (5.7% vs 20.3%).

Conclusions
Adults with severe hypercholesterolemia and without a pathogenic FH variant had less optimal control of cardiovascular risk factors than genetically confirmed FH. One fifth were smokers and one third of all patients included in this study were not taking any lipid-lowering drugs, regardless of the presence of a pathogenic variant.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Swiss Heart Foundation
The association between cholesterol remnants and cardiac structure and function
Authors: Galatius E S , Lassen M C H , Gruntvig Skaarup K , Dyrby Johansen N , Galatius S , Biering T , Boje Jensen G , Schnohr P , Moegelvang R 
Published: October 2022

Abstract

Background
Cardiac disease is the most common cause of death in Europe and is a rising problem globally. Recently, a causal relationship between ischemic heart disease and cholesterol remnants has been suggested by genetic studies. Additionally, new studies have shown that cholesterol remnants were independently related to later development of ischemic disease in individuals free of known heart disease. Finally, in patients suffering from type 1 diabetes, one study demonstrated an association between cholesterol remnants and cardiac function indicating early signs of cardiac pathology.

Purpose
To investigate whether cholesterol remnants are associated with alterations in cardiac structure and function, as evaluated by sensitive echocardiographic measures, in individuals from the general population without known heart disease.

Methods
The study sample consisted of 3,792 participants from a general population cohort without known heart disease. All participants had blood samples withdrawn for analysis and were examined with comprehensive echocardiography including both conventional measurements and two-dimensional speckle tracking analysis. Cholesterol remnant levels were calculated from lipid analyses in non-fasting venous blood samples using the following formula: cholesterol remnants = total-cholesterol − HDL-cholesterol − LDL-cholesterol.

Results
In multivariable analyses increasing levels of cholesterol remnants were associated with significant alterations in cardiac function, demonstrated as a decrease in left ventricular ejection fraction (β=−0.686, P=0.001), a decrease in E/A ratio (β=−0.109, P&lt;0.001) and a decrease in global longitudinal strain (β=−1.195 P=0.014) (Figure 1). The multivariable model was adjusted for age, sex, body mass index, hypertension, diabetes and smoking status. This association was significantly stronger than the association with cardiac alterations and LDL levels with the most significant difference regarding LVEF (cholesterol remnants: β=−0.158, P&lt;0.001) and (LDL: β=−0.016, P=0.353). Additionally, increasing levels of cholesterol remnants were associated with alterations in cardiac structure (IVSd, LVIDd, LVPWd, LVMi and RWT) in the univariable analysis, but these associations were attenuated after multivariable adjustment.

Conclusion
In a general population sample without known heart disease, alterations in cardiac function expressed as both impaired systolic and impaired diastolic function were present with increasing levels of cholesterol remnants. This association was stronger than the association between the cardiac alterations and LDL-cholesterol levels. The findings support the need for testing treatment options aimed specifically at cholesterol remnants, also in the general population.

Funding Acknowledgement
Type of funding sources: None.
The effect of bariatric surgery on circulating levels of lipoprotein(a): a systematic review and meta-analysis
Authors: Jamialahmadi T , Reiner Z , Alidadi M , Kroh M , Almahmeed W , Ruscica M , Sirtori C , Santos R D , Banach M , Sahebkar A 
Published: October 2022

Abstract

Background
Obesity, and especially severe obesity, are strongly related to higher risk of atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality. Bariatric surgery is an effective weight loss therapy for people with severe obesity and weight-related co-morbid conditions. Elevated plasma level of lipoprotein(a) [Lp(a)] is causally associated with ASCVD.

Purpose
The aim of the present meta-analysis was to analyze whether bariatric surgery could influence Lp(a) concentrations.

Methods
A systematic literature search in PubMed, Scopus, Embase, and Web of Science was performed from inception to May 1st, 2021. A random-effects model and the generic inverse variance weighting method were used to compensate for the heterogeneity of studies in terms of study design, treatment duration, and the characteristics of the studied populations. A random-effect meta-regression model was used to explore the association with an estimated effect size. Evaluation of funnel plot, Begg's rank correlation and Egger's weighted regression tests were used to assess the presence of publication bias in the meta-analysis.

Results
Meta-analysis of 13 studies including 1,551 patients showed a significant decrease of circulating Lp(a) after bariatric surgery (SMD: −0.438, 95% CI: −0.702, −0.174, p&lt;0.001, I2: 94.05%). The results of meta-regression did not indicate any significant association between the changes in Lp(a) and duration of follow up from surgery, reduction in body mass index, or baseline Lp(a) concentration. The reduction in circulating Lp(a) was robust in the leave-one-out sensitivity analysis.

Conclusions
Based on the results of the Mata-analysis we showed that bariatric surgery significantly decreases circulating Lp(a) concentrations.

Funding Acknowledgement
Type of funding sources: None.