bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term prognostic value of trimethylamine N-oxide in community-based adults and patients with coronary heart disease
Authors: Bjornestad E , Dhar I , Svingen G F T , Pedersen E R , Orn S , Svenningsson M , Tell G S , Ueland P M , Sulo G , Laaksonen R , Nygaard O 
Published: October 2022

Abstract

Background
Trimethylamine N-oxide (TMAO) is an amine oxide generated by gut microbial metabolism. Emerging evidence suggests pro-atherosclerotic and pro-inflammatory properties of TMAO; however, the clinical utility of circulating TMAO in risk stratification is uncertain.

Purpose
We prospectively assessed relationships of plasma TMAO with long-term risk of all-cause, cardiovascular (CV) and non-CV mortality in community-dwelling adults and patients with coronary heart disease.

Methods
By Cox modelling, risk-associations were examined in the Hordaland Health Study (HUSK; 6393 community-based adults) and the Western Norway Coronary Angiography Cohort (WECAC; 4132 patients with suspected chronic coronary syndrome).

Results
Median follow-up time was 11.0 and 10.3 years in HUSK and WECAC, respectively. Following adjustments for established CV risk factors in HUSK, the HRs (95% CIs) comparing the 4th vs. 1st TMAO-quartile were 1.11 (0.88–1.40), 0.97 (0.65–1.46) and 1.17 (0.88–1.54) for all-cause, CV and non-CV mortality, respectively. Corresponding risk estimates in WECAC were 1.07 (0.86–1.32), 1.16 (0.83–1.62) and 1.02 (0.77–1.34). Similar results were observed in patients with angiographically significant coronary artery disease and patients with reduced left ventricular ejection fraction.

Conclusion
Plasma TMAO was not predictive of long-term all-cause, CV or non-CV mortality in patients with or without established coronary heart disease. This large-scale study does not support a role of TMAO for patient risk stratification in primary or secondary prevention.

Funding Acknowledgement
Type of funding sources: None.
Acute effects of COVID-19 vaccination on inflammatory, macrovasular and microvascular biomarkers
Authors: Terentes-Printzios D , Gardikioti V , Solomou E , Emmanouil E , Gourgouli I , Xydis P , Christopoulou G , Georgakopoulos C , Dima I , Miliou A , Lazaros G , Pirounaki M , Tsioufis K , Vlachopoulos C 
Published: October 2022

Abstract

Purpose
To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness.

Methods
Thirty-two participants (mean age 37±8 years, 20 men) that received the BNT162b2 mRNA COVID-19 vaccine were studied in 3 sessions in a sequence-randomized, sham-controlled, assessor-blinded, cross-over design. Primary outcome was endothelial function assessed by brachial artery flow-mediated dilatation (FMD), and secondary outcomes were aortic stiffness, evaluated with carotid-femoral pulse wave velocity (PWV), microvascular function that was estimated with hyperemic mean blood flow velocity (HMBFV) of the brachial artery, and inflammation measured by high-sensitivity C-reactive protein (hsCRP) and interleukins (hsIL-6 and hsIL-1b) in blood samples. The outcomes were assessed prior to, and at 8h, 24h post the 1st dose of vaccination, and 8h, 24h and 48h post the 2nd.

Results
There was an increase in hsCRP that was apparent at 24h after both the 1st dose (−0.60 [95% Confidence intervals [CI]: −1.60 to −0.20], p=0.013) and the 2nd dose (max median difference at 48h −6.60 [95% CI: −9.80 to −3.40], p&lt;0.001) compared to sham. Similarly, interleukins also increased. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p=0.037) at 24h post the 2nd dose (Figure). FMD values returned towards baseline at 48h. HMBFV remained unchanged during the 1st dose but at 48h post the 2nd dose was numerically lower than the sham procedure but the difference between the 2 sessions was not statistically significant (max mean difference at 48h 8.6 [95% CI: −0.6 to 17.8], p=0.067).

Conclusions
Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose and a transient deterioration of endothelial function at 24h that returns towards baseline at 48h. These results confirm the short-term cardiovascular safety of the vaccine.

Funding Acknowledgement
Type of funding sources: None.
Alirocumab reduces total coronary plaque burden in patients with familial hypercholesterolaemia and no previous clinical atherosclerotic disease
Authors: Perez De Isla L , Diaz Diaz J L , Romero M J , Muniz Grijalvo O , Argueso R , Sanchez Munoz Torrero J F , Mediavilla J D , Ponte P , Fuentes F , Saltijeral Cerezo A , Alvarez Banos P , Rubio P , Cepeda J M , Padro T , Mata P 
Published: October 2022

Abstract

Background
It is well known that statins, ezetimibe and other lipid lowering treatments such as Evolocumab (PCSK9-Inhibitor) reduce cardiovascular events by decreasing LDL-cholesterol (LDL-C) levels and slowing the progression of coronary atherosclerosis. Nevertheless, cardiovascular (CV) risk remains. Alirocumab, a PCSK9 inhibitor has demonstrated a reduction in cardiovascular events but its relationship with coronary atherosclerosis reduction has not been adequately demonstrated.

Purpose
The ARCHITECT trial sought to determine whether Alirocumab 150 mg/2 weeks is able to stop or reverse coronary atherosclerosis progression, by assessing coronary plaque burden (CPB) by serial multidetector computed tomography (MDCT).

Methods
A total of 104 patients with molecularly characterized heterozygous familial hypercholesterolaemia (FH) without clinical cardiovascular disease were enrolled in this trial. Patients had to have CPB &gt;30% as documented by MDCT, be on maximum tolerated statin therapy with or without ezetimibe and LDL-C &gt;100 mg/dL. Patients underwent a MDCT at enrollment and after 18-month treatment with alirocumab and they were analyzed by means of QAngio CT (Medis medical imaging system, the Netherlans). The pre-specified primary endpoint was change in CPB.

Results
Median age was 53.3 (46.2–59.4) years (54, 51.9% woman). Median LDL-cholesterol was 138.9 mg/dL. There was a significant reduction in the primary endpoint as Alirocumab reduced CPB from 34.6 (32.9–36.8)% to 30.4 (27.4–33.4)%. Significant reductions in LDL-C (67%) and atherosclerotic plaque volume were also found. Plaque regression as estimated by CPB was found in 91 (87.5%) patients. Main resuts may be found in figure 1.

Conclusions
Alirocumab demonstrated significant regression of CPB on MDCT over 18 months. ARCHITECT provides crucial mechanistic clues on coronary plaque behavior under the use of Alirocumab and its results could link and explain ODYSSEY-OUTCOMES results.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Sanofi
Coronary CT angiography derived pericoronary inflammation and bespoke cardiovascular risk prediction in the lipid clinic: beyond the calcium score
Authors: Graby J , Sellek J , Khavandi A , Loughborough W , Hudson B J , Shirodaria C , Downie P , Antoniades C , Rodrigues J C L 
Published: October 2022

Abstract

Background
Dyslipidaemia promotes atherosclerosis. Genetic dyslipidaemias, Familial Hypercholesterolaemia (FH) being the most common, are associated with heightened risk of coronary artery disease (CAD) and premature major adverse cardiovascular events (MACE). However, this risk is both heterogeneous and modifiable with treatment.
CT coronary imaging can identify subclinical atherosclerosis, enabling personalised risk stratification and treatment targets. Coronary artery calcium scoring (CACS) is current first-line in European guidelines for asymptomatic patients. However, calcification occurs late in CAD pathogenesis and CACS has low specificity in young patients with severe FH. CT coronary angiography (CTCA) assesses non-calcific plaque and high-risk plaque (HRP) features unappreciable with CACS. Additionally, the pericoronary fat attenuation index (FAI) measures inflammation on routine CTCA and is the strongest non-invasive imaging biomarker of risk of fatal MI.

Purpose
To quantify and compare the reclassification of subclinical atherosclerosis burden in Lipid Clinic patients assessed via CACS vs CTCA with FAI analysis.

Methods
Analysis of a prospectively maintained clinical database of asymptomatic Lipid Clinic patients with both CACS and CTCA imaging from May 2019 to December 2020. CACS was reported with the standardised Agastston criteria and compared with (i) the CTCA-derived Coronary Artery Disease – Reporting and Data System (CAD RADS) grading of anatomical stenosis, including a modifier for HRP features, and (ii) FAI analysis. Significance was defined as two-tailed p75th percentile vs age and sex matched controls) was seen in 6/27 (22%) patients with none to mild calcification on CACS and 6/28 (21%) patients with none to mild CAD on CTCA, of whom 3/7 (43%) had HRP. High FAI was seen in all groups of calcification severity and CAD RADS score (Figure 2). The proportion with high FAI was higher in CAD RADS 0 vs CAD RADS 4, and CACS severity was not associated with level of inflammation (p=0.94).
High FAI was observed in 16% of patients on treatment, suggesting treatment failure. This included patients with CACS ranging from 0 to severe (&gt;400), and CAD RADS of minimal (1) to severe (4).

Conclusion
CTCA re-stratifies CAD presence and severity vs CACS in a high-risk, asymptomatic patient group and identified a high proportion of patients with HRP features. FAI provides incremental value in identification of patients at risk of future MACE regardless of CACS grade, including patients without evidence of overt CAD. Identifying high FAI on treatment may imply treatment failure.

Funding Acknowledgement
Type of funding sources: None.
Impact of antihypertensive medication regimens on blood pressure control in individuals with established coronary heart disease
Authors: Brennan S , Costigan O , McEvoy J W 
Published: October 2022

Abstract

Background and purpose
Hypertension is a major risk factor for coronary heart disease (CHD) development and progression, with pharmacological control of blood pressure reducing the risk of CHD events and death [1].
Treatment and control of blood pressure in CHD is suboptimal, with many patients failing to achieve guideline-directed targets [1,2]. This study aims to assess the relationship between antihypertensive medication regimens and blood pressure control in patients with hypertension and established coronary heart disease.

Methods
The iASPIRE study recently evaluated secondary prevention in an Irish cohort with coronary heart disease [2]. Based on a method used in a similar study [3], we calculated the average percentage daily dose of each prescribed antihypertensive agent. We then assessed the relationship between dose and number of antihypertensive agents with blood pressure control.

Results
540 (75.5%) of iASPIRE participants had an underlying diagnosis of hypertension, and at the study examination, 56% of these had a blood pressure ≥140/90 mmHg, while 83% had a blood pressure ≥130/80 mmHg. The median number of antihypertensive agents prescribed was 2 (IQR 1–2), with 88% of those with hypertension on at least one blood pressure medication. In participants with hypertension on treatment, the median percentage daily medication dose was 29% (IQR 14–50). After adjustment for age and sex, the addition of further antihypertensive medications increased the odds of achieving a blood pressure target of &lt;130/80 mmHg (OR 1.3, 95% CI 1.07–1.69, p=0.012). The average percentage daily dose of each antihypertensive agent was lower in both participants with a medication-controlled blood pressure of &lt;130/80 mmHg and &lt;140/90 mmHg compared to those without blood pressure control (30% versus 37% p=0.006 and 33% versus 38% p=0.028 respectively).

Conclusion
Many patients with hypertension and coronary heart disease currently fail to achieve blood pressure control. This analysis found that an increasing number of antihypertensive medications but not increasing dose was associated with better blood pressure control. Combination therapy is superior to sequential monotherapy in the treatment of hypertension [1], and an approach that emphasises the initiation of several antihypertensive agents would likely lead to better blood pressure control in individuals with coronary heart disease.

Funding Acknowledgement
Type of funding sources: None.
Late gadolinium enhancement patterns in severe symptomatic high-gradient aortic stenosis
Authors: Maltes S , Abecasis J , Santos R R , Oliveira L , Mendes G S , Guerreiro S , Lima T , Freitas P , Ferreira A , Cardim N , Gil V M , Mendes M 
Published: October 2022

Abstract

Background
Left ventricular (LV) remodeling in patients with severe aortic valve stenosis (AS) is a complex process that goes beyond hypertrophic response and may involve reparative/replacement fibrosis. Currently, cardiac magnetic resonance (CMR) is the gold-standard imaging technique for detecting focal myocardial fibrosis through late gadolinium enhancement (LGE). However, myocardial fibrosis prevalence and distribution is quite variable among series. Our goal was to assess LGE prevalence and distribution pattern in severe symptomatic high-gradient AS.

Methodology
Single-center prospective cohort of 132 patients with severe symptomatic high-gradient AS (mean age 73±11 years; 48% male, mean valvular transaortic gradient 60±20 mmHg; mean aortic valve area 0.7±0.2 cm2/m2; mean LV ejection fraction by 2D echocardiogram 58±9%), all with normal flow (except one) undergoing surgical aortic valve replacement. Those with previous history of acute myocardial infarction, ischemic cardiomyopathy or other cardiomyopathy were excluded. All patients performed 1.5T CMR assessment with LV myocardium tissue characterization prior to surgery. Segmental LGE presence was assessed by two independent operators and classified according to the AHA 16 segment model, using 5-standard deviations from remote myocardium as the signal intensity cut-off for LGE identification and quantification.

Results
Overall, 96 patients (74%) had non-ischemic LGE (median LGE mass 3.2 g [IQR 0.2–8.3] g; median percentage of LGE myocardial mass 2.5% [IQR 0.1–6.1]%); 22 patients [17%] with exclusively junctional LGE); in one patient an incidental ischemic scar (subendocardial distribution) was identified. No cases of subepicardial distribution were found. Intramyocardial LGE was most frequently observed in basal and mid-anterior and inferior interventricular septum – see Figure 1. In these segments, LGE was most often junctional at right-ventricular insertion points (54%), followed by mid-wall LGE (32%) or both sites involvement (14%).

Conclusion
LGE is frequent in symptomatic high-gradient AS patients with preserved left ventricular ejection fraction, most often presenting as junctional enhancement in basal/mid-anterior and inferior interventricular septum. Future studies may address whether distinct LGE patterns may impact patient prognosis.

Funding Acknowledgement
Type of funding sources: None.
Could cholesterol remnants predict long-term cardiovascular events after NSTACS?
Authors: Martinon-Martinez J , Alvarez Alvarez B , Gonzalez Ferrero T , Garcia-Rodeja Arias F , Otero Garcia O , Jimenez Ramos V , De La Fuente Rey A , Cacho Antonio C , Cid Alvarez B , Iglesias Alvarez D , Agra Bermejo R , Rigueiro Veloso P , Garcia Acuna J M , Gonzalez Juanatey J R 
Published: October 2022

Abstract

Introduction
The remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease. However, the prognostic impact of elevated RC levels in patients with non-ST-elevation acute coronary syndrome have not been established in the current population. Then, our objetive is investigated the effect of RC in terms of long-term mortality in patients admitted for NSTACS

Methods
This is an observational study in which we included all patients discharged from cardiology for ACS in two centers from 2003 to 2018. Patients were classified by low RC values &lt;23 mg/dL or high RC values ≥24 mg/dL in the first blood count performed during hospitalization. We analyzed the effect of RC (continuous variable) on all-cause mortality, cardiovascular mortality and MACE using the Cox regression model adjusted for several confounding variables.

Results
We included 5685 patients diagnosed with ACS, with a mean age of 66.50 (SD ±13.20) years, 27.1% female. The baseline, during admission and discharge characteristics are shown in table (1 and 2).
During follow-up (median 56 months, IQR 21–79 months) there was an increased risk of all-cause mortality in patients with higher levels os RC unadjusted and adjusted for several factors (age, sex, GRACE, early coronariography, hypertension, treatment at discharge), HR (1.003, CI 1.000–1.005, p 0.003). Similar results were observed for cardiovascular mortality (HR 1.003, CI 1.000–1.006, p 0.003), and MACE (HR 1.002, CI 1.000–1.003, p 0.002)

Conclusion
RC could have prognostic impact in the long-term follow up in patients with NSTACS, even after adjusting for risk factors and evidence-based treatments. There results should be taken under consideration for the treatment and management of NSTACS patients.

Funding Acknowledgement
Type of funding sources: None.
Heavy weekly alcohol consumption versus binge drinking after an acute coronary syndrome and risk of major adverse cardiovascular events at one year follow up
Authors: Tessitore E , Branca M , Heg D , Nanchen D , Auer R , Raber L , Klingenberg R , Windecker S , Luscher T F , Matter C M , Rodondi N , Carballo D , Mach F , Gencer B 
Published: October 2022

Abstract

Background
The association between heavy weekly alcohol consumption or binge drinking and the risk of major adverse cardiovascular events (MACE) after acute coronary syndromes (ACS) is still unclear.

Purpose
To determine the risks of MACE at one year follow up according to baseline alcohol consumption, especially in patients with heavy weekly alcohol consumption or binge drinking.

Methods
We analyzed data of 6053 patients hospitalized in 4 Swiss centres for an ACS and followed over 12 months. Data on alcohol consumption were collected at baseline and at one year follow up after ACS. Binge drinking was defined as the consumption of ≥6 units of alcohol on one occasion, for the 12-months period preceding the one-year follow up. We defined MACE as a composite of cardiac death, myocardial infarction, stroke or clinically indicated target vessel coronary revascularization. We applied Cox regression to assess the risk of MACE associated with heavy alcohol weekly consumption (&gt;14 standard units/week) compared to light consumption (&lt;1 standard unit/week) or abstinence, as well as the risk with binge drinking, compared to no binge drinking, adjusting for baseline differences (age, sex, body-mass index, smoking, diabetes, peripheral artery disease, stroke, hypertension, use of aspirin, anticoagulation, statin, beta-blocker, ACE-inhibitor or ATII receptor blocker).

Results
At baseline, 817 (13.4%) patients reported heavy weekly alcohol consumption and 717 (11.8%) reported to have at least one episode of binge drinking per month. The risk for MACE at one year follow up was not increased in those with heavy weekly consumption compared to light consumption (8.7% vs. 8.5%, HR 0.96, 95% CI 0.69–1.33, P=0.80) or no consumption (8.7% vs. 10.3%, HR 1.26, 95% CI 0.88–1.80, P=0.21). However, the risk of MACE was higher in those reporting binge drinking with less than one episode a month (9.4% vs. 7.7%, HR 1.67, 95% CI 1.32–2.12, P&lt;0.001), as well as in those with at least one episode of binge drinking per month (13.4% vs. 7.7%, HR 2.07, 95% CI 1.62–2.65, P&lt;0.001), when compared to no binge drinking.

Conclusion
In contrast to regular heavy alcohol consumption, binge drinking behavior is associated with significant increased risk of MACE 12 months after ACS.

Funding Acknowledgement
Type of funding sources: None.
Dementia in individuals with severe hypercholesterolemia: Korean nationwide cohort study
Authors: Lee S H , Lee C J , Park S , Han K 
Published: October 2022

Abstract

Background
Dementia risk and benefit of lipid lowering in individuals with severe hypercholesterolemia has not been well studied. The aim of this study was to evaluate the risk of dementia and effect of lipid lowering in this population using nationwide cohort.

Methods
This study was performed using the National Health Insurance Service database of Korea. Among individuals who took health check-up and were followed-up, 1,584,401 were enrolled and analyzed. Study population were categorized to three groups with severe hypercholesterolemia according to LDL-C levels, &gt;260, 225–259, and 190–224 mg/dL groups, and a control group (&lt;160 mg/dL). Risks of incident dementia (all dementia, Alzheimer's disease, and vascular dementia) were compared. In the subgroup with new statin users, the effect of statins was further analyzed according to post-treatment LDL-C levels (&lt;70, 70–99, 100–129, &gt;130 mg/dL).

Results
In the median follow-up of 6.1 years, all dementia occurred up to 5.41/1000 person-year in the groups with severe hypercholesterolemia. Adjusted hazard ratios (aHRs) of all dementia in the groups ranged from 1.05 to 1.34 (p=0.023) and were dependent of LDL-C categories. Alzheimer's disease developed up to 4.94/1000 person-year and aHRs ranged from 1.04 to 1.38 (p=0.040) with the same pattern to all dementia. Vascular dementia occurred up to 0.59/100 person-year and aHRs ranged from 1.03 to 1.57 without significant difference according to LDL-C categories. In the median follow-up of 6.2 years in new statin users, aHRs were 0.69 to 0.92 for all dementia and 0.74 to 0.92 for Alzheimer's disease, and 0.53 to 1.15 for vascular dementia according to post-treatment LDL-C levels. However, the risk was not significantly related to the levels.

Conclusions
This study newly showed elevated risk of dementia, particularly Alzheimer's disease, in patients with severe hypercholesterolemia. The benefit of active lipid lowering on this neurological disease needs to be proven by further studies.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): Korean Society of Lipid and Atherosclerosis; National Research Foundation of Korea