bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between vitamin D receptor gene polymorphism and essential hypertension: a systematic review and meta-analysis
Authors: Addai M F , Maulana R , Widyantoro B
Published: October 2022

Background and aim

Recent publications reported that the association between Vitamin D Receptor (VDR) gene polymorphism of Fokl (rs228570 or rs10735810) and essential hypertension (EH) remains controversial. Thus, we conducted this study to investigate the relationship between Fokl and EH.

Methods

Major medical databases (EMBASE, PUBMED, Science Direct, Cochrane, Springer, Scopus, ProQuest, and Lilacs) were systematically searched for observational studies evaluating the impact of Fokl polymorphism on EH, published until January 2022 with predefined protocol and without language restriction regarding PRISMA guideline. Analysis was performed in RevMan 5.3 (fixed and random-effects model through heterogeneity test) to provide pooled measures for odds ratio (OR) under Hardy-Weinberg Equilibrium based-on allele contrast, additive, dominant, and recessive genetic models.

Results

Eight observational studies enrolled comprising 3,762 cases and 4,445 controls. Under the allele model, Fokl polymorphism (f vs F) significantly increased the odds of having EH (OR=1.27; 95% confidence interval: 1.05–1.53), p=0.01. Fokl polymorphism was not significantly associated with EH under additive model (ff vs FF) with OR=0.94 (0.57–1.54), p=0.79, dominant model (Ff + ff vs FF) with OR=0.97 (0.8–1.16), p=0.76 and recessive model (FF + Ff vs ff) with OR=0.96 (0.59–1.56), p=0.97 However, subgroup analysis based on ethnicities, comprising Asian, European, American, and African, showed that only in African population, Fokl polymorphism was associated with reduced odds of EH under additive (OR=0.36; 0.17–0.74), p=0.005 and recessive model (OR=0.31; 0.14–0.7), p=0.005.

Conclusions

VDR gene polymorphism of Fokl was significantly associated with EH in a particular genetic model and could be affected by ethnicity. However, further studies are needed to make the robust evidence.

Funding Acknowledgement

Type of funding sources: None.
The diastolic blood pressure U-curve
Authors: Rocha Carvalho P , Moreira I , Carvalho C , Bernardo M , Monteiro J , Fontes P , Moreira J I
Published: October 2022

Introduction

It is known that low diastolic blood pressure (DBP) at admission is associated with short-term cardiovascular events after acute coronary syndrome (ACS). However, there is a lack of further investigation into the nonlinear relationship between admission diastolic blood pressure (DBP) and adverse outcomes of ACS patients.

Objective

To investigate the relationship between admission diastolic blood pressure and subsequent cardiovascular mortality in patients with acute coronary syndrome.

Methods

Retrospective study of patients with ACS periodically included in our center registry between October/2012 and September/2018. Patients with class killip 4 at admission or that needed ionotropic support during hospitalization were excluded. The association between admission DBP and cardiovascular mortality during the follow-up period among this population was analyzed using multivariate COX regression model. Results were presented according to DBP quartiles: Q1, less than 70 mm Hg; Q2, from 71 to 80 mm Hg; Q3, from 81 to 90 mm Hg; Q4, above 90 mmHg.

Results

A total of 548 patients were included in this cohort study. Mean patient age was 65.9±13.1 years and 75.2% were men. A nonlinear relation was observed between DBP at admission and cardiovascular mortality over the follow-up.

During a median follow-up of 42 months (IQR: 27–59), 47 patients (8.6%) died from cardiovascular causes. After adjusting for potential confounders (age and diabetes mellitus), patients in Q3 had the lowest risk for cardiovascular death by Cox proportional hazard model (HR 0.44; 95% CI: 0.16–1.00). Meanwhile, compared with Q1, Q3 patients had significantly lower risk for cardiovascular death (HR 0.35, 95% CI: 0.13–0.92).

Conclusion

Among patients admitted for ACS, there is a U curve relationship between admission DBP and risk for cardiovascular death. These results could be explained by a reduction in diastolic coronary blood flow which influences myocardial oxygen supply relative to the necessary demand in an ACS.

Funding Acknowledgement

Type of funding sources: None.
PR interval as arisk factor for atrial fibrillation in patients with arterial hypertension
Authors: Papakonstantinou P , Andrikou I , Konstantinidis D , Tsioufis C
Published: October 2022

Introduction

Hypertension (HTN) is one of the most important risk factors associated with atrial fibrillation (AF). Prolongation of the PR interval has been associated with an increased risk of incident AF, while PR interval is a component of the Framingham risk score for AF. However, the results regarding PR prolongation as a risk factor for AF are inconsistent.

Purpose

We aim to evaluate the predictive role of the PR interval for AF development in a large cohort of HTN patients.

Methods

Consecutive patients with essential hypertension without known AF at baseline were followed up for a mean period of 5.3±3.3 years. A 12-lead ECG and an echocardiography study were performed on each patient at baseline and annually, and 24h Holter rhythm monitoring was used in the event of arrhythmia symptoms. Routine clinical and paraclinical examinations as well as medications were implemented during the follow-up period according to the European Society of Cardiology/ European Society of Hypertension guidelines for HTN management. The PR interval and P wave duration were obtained from the baseline ECG.

Results

We included 1807 hypertensives (mean age 57±11 years; 49% males) with office systolic blood pressure (SBP)/ diastolic blood pressure (DBP) 144±17/89±11mmHg. During the follow-up period, 65 cases (3%) of new-onset AF were recorded. Patients with new-onset AF (n=67) compared to those without AF (n=1740) had greater baseline P wave duration (115 vs 110 ms) and PR internal (174 vs 157 ms). Multivariable Cox regression analysis showed that higher baseline PR internal is significantly associated with the development of AF (HR 1.01, 95% CI 1.01–1.02; p=0.01), while there was no significant predictive value for baseline P wave duration on the incidence of new-onset AF. Baseline increased DBP was associated with a higher incidence of AF (HR 1.05, 95% 1.003–1.091; p=0.037).

Conclusions

Baseline PR internal is a significant predictor of new-onset AF in hypertensive patients. The PR prolongation could be considered as a marker for cardiovascular degenerative aging caused by vascular inflammation and myocardial fibrosis.

Funding Acknowledgement

Type of funding sources: None.
Screening for familial hypercholesterolaemia; extending a role for blood programs in promoting public health
Authors: Eason S , Khera A , Gore O , Sayers M H
Published: October 2022

Background

Familial hypercholesterolaemia (FH) is a genetic disorder characterized by high levels of cholesterol with evidence of coronary arterial disease at an early age. The prevalence of FH has been recently reported as 1/200 to 1/250 in the general population and although early identification and treatment is recommended (2019 ESC/EAS Guidelines for the Management of Dyslipidaemias), the disorder is largely underdiagnosed in asymptomatic individuals.1

A number of blood programs has recognised the opportunity that blood donation provides to identify ostensibly healthy individuals who might be unaware of risks to their health. These programs have included, along with mandated serological testing, such assays as non-fasting total cholesterol (TC) and haemoglobin A1C. They have also taken steps to notify individuals whose results suggest risk for cardiovascular disease or diabetes.

Purpose

Since our blood donation program has a long history of providing donors information about their TC, we tested whether some donors with elevated TC met the criteria for FH.

Methods

We reviewed unlinked total non-fasting cholesterol results from volunteers donating between 2015 and June 2019. Cholesterols were measured on a chemistry analyzer system (Beckman Coulter AU680) on residual blood after routine testing for infectious disease markers. For volunteers donating more than once, we included only their highest TC recording. TC was classified by American Heart Association (AHA) 2020 Goal Metrics as high, if ≥240 mg/dL (6.2 mmol/L) in donors ≥20 years of age and ≥200 (5.1 mmol/L) in donors <20 years of age. 2 We applied the United States Center for Disease Control Cooperative MEDPED diagnostic criteria for FH. Using these criteria, FH is diagnosed when TC exceeds 270 mg/dL (7.0 mmol/L) in individuals less than 20, 290 mg/dL (7.5 mmol/L) in individuals 20 to 29, 340 mg/dL (8.8 mmol/L) in individuals 30 to 39, and 360 mg/dL (9.3 mmol/L) in individuals 40 years of age and older. 3

Results

There were 432,389 unique donors during the study period. The overall prevalence of high cholesterol, 11.1% and the prevalence of FH 0.24% are similar to published data for the general population. As shown in the table, the prevalence of FH was highest in blood donors 20 to 29 years of age and was lower in those over 30 years, while the prevalence of high TC was higher in older age groups.

Conclusion

There is a subset of blood donors, at all ages who can be identified as satisfying familial hypercholesterolaemia criteria that could benefit from additional evaluation and family screening. A sizeable proportion of blood donors have high cholesterol despite not having FH.

Funding Acknowledgement

Type of funding sources: None.
Preterm birth, abnormal foetal growth and the risk of atrial fibrillation later in life: a cohort study in Denmark, Finland and Sweden
Authors: Yang F , Janszky I , Gissler M , Obel C , Cnattingius S , Roos N , Miao M H , Yuan W , Li J , Laszlo K D
Published: October 2022

Background

Increasing evidence suggests that adverse birth outcomes, including preterm birth, small for gestational age (SGA) and large for gestational age (LGA), are associated with increased risks of hypertension, ischemic heart disease, stroke and heart failure. However, knowledge regarding their associations with atrial fibrillation (AF) is limited and inconsistent.

Objective

To investigate whether preterm birth, SGA and LGA are associated with increased risks of AF later in life.

Methods

We conducted a population-based cohort study involving 8,012,433 live singleton births based on the nation-wide Danish (1978–2016), Swedish (1973–2014) and Finnish (1987–2014) Medical Birth Registers. Information on birth outcomes, atrial fibrillation and covariates was obtained from nationwide health and socioeconomic registers. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for AF according to preterm birth (<37 weeks), SGA and LGA (<10th and >90th birth weight for gestational age percentiles, respectively) with multivariable Cox proportional hazard models and flexible parametric survival models. We conducted sibling analyses to control for unmeasured familial risk factors.

Results

Preterm birth and LGA were associated with increased AF risks in both the full population cohort and in the sibling analyses; the multivariate HRs (95% CI) from the cohort analyses were 1.53 (1.37–1.71) and 1.55 (1.44–1.65), respectively. The associations were stronger with AF in childhood than in adulthood. Children born SGA had an increased risk of AF in the first 18 years of life, but not later.

Conclusions

Individuals born preterm or LGA had an increased AF risk independently of familial confounding factors. Individuals born SGA had an increased AF risk only during childhood. Persons born prematurely or with abnormal foetal growth may benefit from early screening and prevention to reduce the risk of AF later in life.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Council for Working Life and Social Research; China Scholarship Council
An observational analysis of trends in rheumatic heart disease incidence and mortality in EU15+ countries over 29 years
Authors: Ojha U , Marshall D , Salciccioli J , Al-Khayatt B , Goodall R , Borsky K , Crowley C , Shalhoub J , Hartley A
Published: October 2022

Background

Rheumatic heart disease (RHD) is a debilitating sequela of acute rheumatic fever (ARF), caused by Group A streptococcus (GAS) infection. Repeated episodes of ARF results in valvular damage over time. As a preventable disorder which was once common worldwide, RHD has largely been eradicated in affluent nations due to widespread availability of penicillin, improvement in socioeconomic standards and advancements in health and social infrastructures. However, it has been speculated that the global refugee crisis, especially in Europe, might contribute to a resurgence of RHD cases in these regions.

Purpose

This observational study aimed to analyse trends in RHD incidence and mortality rates in European Union 15+ (EU15+) over a 29-year period.

Methods

Data was obtained from the Global Burden of Disease database. Age-standardised mortality and incidence rates for RHD were extracted for the EU15+ countries for the years 1990–2019. Trends were subsequently analysed using Joinpoint regression analysis.

Results

Over the 29-year period, an overall declining trend in RHD incidence and mortality across EU 15+ nations was observed. The United Kingdom demonstrated the largest decrease in RHD incidence amongst females (−54.9%) and Finland amongst males (−55.3%). Both RHD incidence and mortality were higher among females compared to males across EU15+ countries over the observed period. The most recent incidence trends, starting predominantly after 2014, demonstrated a rise in RHD incidence in most countries. For both sexes, increases were seen in Australia, Belgium, Ireland, Italy, Netherlands, Norway, Sweden and USA. For males specifically, increase in RHD incidence was seen in Spain, and Finland, and for females only in Canada and Ireland. The recent increasing RHD incidence rates ranged from +0.4% to + 24.7% for males and +0.6% to +11.4% for females.

Conclusion

Whilst overall there are decreases in incidence and mortality from RHD, we observe more than half of EU15+ countries have increasing incidence trends in RHD in recent years. This increasing trend primarily started after 2014, overlapping with the start of the European migration crisis. Although speculative, disparities in access to healthcare for migrants, amongst other socioeconomic factors, may be potential causes; subsequently, further efforts by governments and public health officials are required to recognise and control the resurgence of RHD in high income nations.

Funding Acknowledgement

Type of funding sources: None.
Cardiometabolic multimorbidity and lifetime risk of atrial fibrillation among men and women
Authors: Lu Z , Ntlapto N , Tilly M , Ikram M A , De Groot N M S , Kavousi M
Published: October 2022

Background

Atrial fibrillation (AF) is the most common cardiac arrythmia worldwide, with an increased risk of comorbidity, and significant sex differences in pathophysiology and prognosis. Cardiometabolic disorders, including obesity, hypertension, diabetes mellitus, coronary heart disease, stroke, and heart failure commonly coexist with AF. However, the sex-specific patterns and (combined) impact of cardiometabolic disorders on the risk of new-onset AF remains largely unknown.

Purpose

To examine the association between patterns of cardiometabolic multimorbidity and new-onset AF and lifetime risk of AF incidence among men and women.

Methods

4,113 men and 5,432 women free of prevalent AF at baseline (from 1996 to 2008) from the Rotterdam Study were included. AF incidents were assessed by electrocardiograms and general practitioners' and hospital records, and followed up to January 1st, 2014. Sex-specific Cox proportional hazards regression models were used to assess the association between the amount of cardiometabolic disorders and risks of new-onset AF. Models were adjusted for traditional cardiovascular risk factors. Remaining lifetime risk for AF was estimated across the cardiometabolic multimorbidity groups at index ages of 55, 65, and ≥75 years up to age 108.

Results

Mean age at baseline was 65.5±9.4 years. Median follow-up time was 10.8 years. In the fully-adjusted model, a significant association was found between the amount of cardiometabolic disorders and incident AF among women but not men. Compared to women without cardiometabolic disorders, women with 3 (hazard ratios, 95% conference intervals: 2.17 (1.24–3.79)) and ≥4 comorbidities (4.58 (2.22–9.48)) had higher AF risks. The lifetime risk for AF was significantly increased with the number of cardiometabolic disorders among both men and women. At index age of 55 years, the lifetime risks (95% confidence interval) for AF were 25.2% (17.1–33.4), 24.2% (20.0–28.9), 27.1% (23.2–31.0), 30.0% (24.3–35.7) and 34.1% (22.4–45.7), for 0, 1, 2, 3, and ≥4 comorbid cardiometabolic disorders among men, respectively. Corresponding risks were 16.3% (6.68–25.9), 20.3% (16.3–24.3), 27.6% (24.1–31.2), 23.6% (17.8–29.4) and 33.3% (16.0–50.2) among women.

Conclusions

We observed a significant combined impact of cardiometabolic disorders on AF risk, most evidently among women. Participants with cardiometabolic multimorbidity had a significantly increased lifetime risk of AF, especially at a young index age.

Funding Acknowledgement

Type of funding sources: None.
COVID-19 pandemic and cardiovascular mortality and morbidity in the Czech Republic
Authors: Bruthans J , Rychtarikova J , Jarkovsky J
Published: October 2022

Background

During 2020–2021 the Czech Republic was hit by several waves of COVID-19 epidemic. 1,700,000 acquired the disease and in 39,000 this was the main cause of death, making the Czech Republic one of the most affected countries. But there was also a considerable increase in CV (cardiovascular) mortality. Due to repeated lockdowns and further restrictions the CV medical care was restricted.

Purpose

To learn about the impact of covid pandemics on CV health we performed further analyses.

Methods

We analysed the 2019–2021 data of CV mortality, CV hospital and outpatient treatments and data on risk profiles of CV patients. The analysis was based on the Czech Mortality and Hospitalization Register and Health Insurance Register (data about health care provided) from the Institute for Health Information and Statistics of the Czech Republic.

Results

The total CV mortality 2019–2021, after years of declining CV mortality, increased from 47,393 in 2019 to 51,299 in 2021 (8.24%), slightly less in women than in men. The mortality from acute coronary syndrome (ACS, I20–I24) decreased from 4287 to 4182 (2.45%), mortality for chronic CHD (I25) increased from 18,049 to 19,216 (6.47%), for pulmonary embolism (I26) from 824 to 867 (5.2%), for sudden cardiac death and heart arrest from 1143 to 1276 (increase 11.6%). Mortality for heart failure (I50) increased from 5477 to 6728 (22.8%), for stroke (I60-I64) did not change: from 5406 to 5426 (+0.4%), for arterial hypertension increased from 3923 to 4822 (22.9%). There was a shift from inhospital to outhospital CV mortality. Hospital admissions for ACS declined by 40% to recover to former numbers in the second half of 2021. In the outpatient CV care there was a decrease in clinical and laboratory investigations. Based on data from the Czech AH excellence centers of the ESH, with the first lockdown the number of patients attending centers decreased by 90% to recover nearly to previous numbers with lifted restrictions and to decrease less with further waves of epidemics. The patients continued drug treatment and home BP measurements. The laboratory controls of hyperlipidaemias and of diabetes were affected in similar way, the impact on blood pressure, lipid and diabetes control needs further analyses. There was increase in prevalence of obesity and substantial decrease in physical activities.

Conclusions

In changing CV mortality, not only morbidity and mortality caused by direct deleterious effect of covid infection on CV system (injury to heart muscle, thromboembolic complications, arrhytmias, etc), but also “colateral damage”, caused by compromised CV medical care and prevention should be considered. The most striking increase in mortality we found in heart failure and arterial hypertension, obviously conditions in need of close medical follow up. Only full restitution of complex CV treatment and prevention will restore positive trends in CV morbidity and mortality.

Funding Acknowledgement

Type of funding sources: None.
No need for a cardiologist for AMI diagnosis – progress of transforming a behemoth telemedicine program with artificial intelligence
Authors: Mehta S , Vieira D , Zerpa D , Guillen V , Carrasquel M , Ramadan S , Martinez F , Rossitto F , Carrera K , Fleming M , Pinos D , Brena-Pastor L , Ozair S , Gonzalez A , Barco A
Published: October 2022

Background

The Latin American Telemedicine Infarct Network (LATIN) Telemedicine is a mammoth hub and spoke model that provides an umbrella of AMI protection for 100 million patients. In the program, 826,043 patients had a telemedicine encounter; 7,400 with AMI were diagnosed; 4,332 of them managed with guidelines-based strategies. We have gradually begun implementing a system for using Artificial Intelligence (AI) algorithms embedded into EKGs for rapid and accurate STEMI detection and validated the results with a cardiologist's interpretations.

Purpose

To test whether an AI-driven EKG algorithm can effectively substitute a cardiologist for STEMI telemedicine protocols.

Methods

The AI algorithm construction was in the following fashion. Sample: a selection of 8,511 EKG and 90,592 classified heartbeats. Pre-processing: segmentation of each EKG into individual heartbeats. Training & testing: 90% and 10% of the total dataset, respectively. Classification: 1-D Convolutional Neural Network; the study constructed classes for each heartbeat. The algorithm was next deployed on a consecutive series of LATIN EKG records to diagnose STEMI. We afterwards compared the algorithm's results with eight expert cardiologists' interpretations of the same sample.

Results

This study achieved a concordance of 91% between the AI algorithm and cardiologist interpretation (Figure 1).

Conclusions

The initial results with AI algorithms for STEMI diagnosis are encouraging and may provide the base work for new tools for cardiologists to improve their efficiency. Moreover, implementing this innovative tool may overcome current limitations associated with the telemedical management of this disease.

Funding Acknowledgement

Type of funding sources: None.
Including measures of chronic kidney disease to improve cardiovascular risk prediction by SCORE2 and SCORE2-OP
Authors: Matsushita K , Kaptoge S , Hageman S H J , Visseren F L J , Pennells L , Coresh J
Published: October 2022

Background

The 2021 ESC guideline on cardiovascular disease (CVD) prevention qualitatively categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, SCORE2 and SCORE2-OP, to predict CVD risk.

Purpose

To develop and validate an “Add-on” to incorporate CKD measures into these algorithms, using a validated approach.

Methods

In 3,054,840 participants from 34 datasets, we developed three Add-ons (eGFR only, eGFR + urinary albumin-to-creatinine ratio [ACR] [the primary Add-on], and eGFR + dipstick proteinuria) for SCORE2 and SCORE2-OP. We validated c-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,995,067 participants from 33 different datasets.

Results

In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved c-statistic by 0.006 (95% CI 0.005–0.008) and 0.018 (0.012–0.024), respectively, for SCORE2 and 0.012 (0.009–0.015) and 0.023 (0.013–0.032), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57,485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI (e.g., 0.100 [0.062–0.138] for SCORE2) compared to the qualitative approach in the ESC guideline.

Conclusion

Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): US National Kidney Foundation funding as well as US NIDDK
Potential impact of replacing SCORE with SCORE-2 on risk classification and statin eligibility – a coronary calcium score correlation study
Authors: Paiva M , Gomes D , Freitas P , Santos R , Presume J , Lopes P , Matos D , Guerreiro S , Santos A , Saraiva S , Mendes M , Ferreira A
Published: October 2022

Background

Recently, the European Society of Cardiology issued new algorithms to estimate the 10-year risk of atherosclerotic cardiovascular disease (ASCVD), along with new age-specific thresholds to classify individuals as low-to-moderate, high, or very-high risk.

The aim of this study was to compare the latest SCORE-2 model with the older SCORE (Systematic COronary Risk Evaluation) in their ability to identify individuals with high coronary artery calcium score (CACS), and assess the relationship between potential eligibility for statin therapy and CACS.

Methods

Individuals 40–69 years old without diabetes or known ASCVD were identified in a single center registry of patients undergoing CACS and coronary CT angiography for suspected coronary artery disease. SCORE and SCORE-2 were calculated and used with each patient's untreated LDL-C values to assess eligibility for statin therapy. High CACS was defined as an Agatston score ≥100.

Results

A total of 389 pts (46% men, mean age 58±8 years) were included, of which 15% (n=60) were active smokers. The mean systolic blood pressure and untreated LDL-C values were 136±17 mmHg and 155±65 mg/dL, respectively.

The proportion of patients classified as low-to-moderate risk, high risk, and very high risk was 93%, 6% and 1% using the SCORE algorithm, and 42%, 44%, and 14% using SCORE-2, respectively. Overall, 218 patients (56%) would have their risk category revised upwards, while no patients would be downgraded.

The median CACS was 5 (IQR 0–71 AU), with 166 patients (43%) having CACS = 0, and 81 (21%) presenting CACS values ≥100.

SCORE and SCORE-2 showed similar discriminative power to identify patients with CACS ≥100 (C-statistic 0.77, 95% CI 0.71–0.82, vs. 0.75, 95% CI 0.69–0.80, P=0.109 for comparison]. The up-reclassification of risk conveyed by SCORE-2 affected patients across all categories of CACS (Fig. 1).

The proportion of patients in whom statin therapy would generally be indicated was higher with the SCORE-2 criteria vs. the SCORE algorithm (61% vs. 29%, respectively, p<0.001). The broadening of potential indication for statin therapy spanned all categories of CACS, including patients with CACS = 0 (Fig. 2).

Conclusion

Even though the discriminative power of SCORE-2 is similar to the older SCORE, the introduction of age-specific thresholds results in the up-reclassification of risk in roughly half of the patients. The application of SCORE-2 will broaden statin eligibility overall, not only in patients with high atherosclerotic burden, but also in those with CACS = 0. These findings support the use of risk modifiers in selected patients to improve the effectiveness of statin therapy.

Funding Acknowledgement

Type of funding sources: None.
Impact of metabolic syndrome and its components on the progression of coronary artery calcification in statin-naive young adults: results from the KOICA registry
Authors: Ahn H J , Lee H S , Han S M , Park H E , Choi S Y
Published: October 2022

Background

Metabolic syndrome (MetS) is known to be associated with the progression of coronary artery calcification (CAC). However, the relative risks of CAC progression according to the presence of MetS and individual components of MetS in young adults are unknown.

Purpose

We investigated the impact of MetS, the number of meeting MetS components (metabolic burden), and each component of MetS on CAC progression in statin-naïve young adults. Also, we evaluated the association between the change of metabolic burden and CAC progression.

Methods

From the KOrea Initiatives on Coronary Artery calcification (KOICA) registry, we included 2,151 asymptomatic adults aged between 20 and 45 years who underwent serial coronary artery calcium scans as a part of health examination. The difference of ≥2.5 between the square roots of coronary artery calcium score at the baseline and follow-up measured by Agatston units was defined as CAC progression. We estimated the risk of CAC progression according to the presence of MetS, individual components of MetS, and metabolic burden using Cox proportional-hazards models. Among young adults with MetS, the impact of the metabolic burden decrement on CAC progression was evaluated by a logistic regression model.

Results

Of 2,151 young adults (mean age 41.3±3.8 years, male 85.4%), 488 (22.7%) adults had MetS at baseline health examination. During a median follow-up of 2.1 years, CAC progression was observed in 325 (15.1%) adults. MetS was significantly associated with an increased risk of CAC progression after adjusting for other cardiovascular risk factors: adjusted hazard ratio (aHR) 2.59, 95% confidence interval (CI): 1.97–3.42, p<0.001. There was a positive linear correlation between metabolic burden and the risk of CAC progression with an approximately 7-fold higher risk in the group having metabolic burden of 4–5 (aHR 7.22, 95% CI: 4.10–12.72, p<0.001) than in the group without. Among each component of MetS, elevated blood pressure (BP), impaired fasting glucose (IFG), and elevated triglycerides (TG) were associated with the risk of CAC progression, demonstrating the strongest contribution of elevated BP (aHR 2.67, 95% CI: 2.00–3.56, p<0.001). Of note, a decrease of more than one metabolic burden in the follow-up examination was associated with the reduced risk of CAC progression in MetS adults than the others: odds ratio (95% CI), 0.46 (0.22–0.98), p=0.044.

Conclusions

In statin-naïve young adults, the metabolic burden is associated with CAC progression in a dose-response relationship. Elevated BP, TG, and IFG are metabolic derangements requiring special attention to care, and an improvement in metabolic imbalance might have a preventive effect on CAC progression.

Funding Acknowledgement

Type of funding sources: None.
Prognostic role of adding a genetic risk score to the new European SCORE2 in a cardiovascular events prediction, in a moderate-risk region
Authors: Temtem M , Palma Dos Reis R , Serrao M , Sa D , Santos M , Soares C , Sousa A C , Rodrigues M , Freitas S , Henriques E , Borges S , Guerra G , Ornelas I , Drumond A , Mendonca M I
Published: October 2022

Introduction

The new SCORE2 provides risk estimates for the combined outcome of fatal and non-fatal cardiovascular disease (CVD) events, in contrast with SCORE's use for CVD mortality only. Genetic predisposition to CVD is not considered in SCORE2 for prevention and treatment.

Purpose

Evaluate the impact of adding a Genetic Risk Score (GRS) to the new European SCORE2 in MACE prediction and estimate the additional value in cardiovascular risk stratification in an asymptomatic Portuguese population.

Methods

A prospective study was performed in a population-based cohort of 1,100 individuals without known CVD and diabetes (mean age 53.3±6.9 years). For all included participants, SCORE2 was calculated and three risk categories were considered: low-, moderate- and high-risk. A 33-SNP GRS was constructed and two groups were analyzed: lower and higher than the GRS median. Kaplan-Meier survival curves were created and a Cox regression model was performed with the two scores to assess MACE risk. C-statistic methodology compared the model between SCORE2 solely and SCORE2 plus GRS.

Results

After Kaplan-Meier analysis for MACE occurrence, the high categories of SCORE 2 and GRS showed worst survival when compared to the lower categories (p<0.0001). Cox regression presented an HR of 8.528 (p=0.001) for high-risk SCORE2 and an HR of 4.520 (p<0.0001) for GRS higher than the median. C-statistic demonstrated that the SCORE2 predictive value was 0.678, increasing to 0.792 when GRS was included (p=0.0005).

Conclusions

In this work, combining SCORE2 with multiple genetic loci gathered into a GRS, improved the identification of patients with the worst prognosis. This new tool may be of great utility in risk stratification in primary prevention. Larger prospective multicenter cohorts with longer follow-up should reproduce and validate these findings.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM
Prognostic impact of adding Coronary Calcium Score to European SCORE2 in an asymptomatic Portuguese population
Authors: Temtem M , Mendonca M I , Serrao M , Santos M , Sa D , Soares C , Sousa A C , Henriques E , Rodrigues M , Freitas S , Borges S , Ornelas I , Drumond A , Palma Dos Reis R
Published: October 2022

Introduction

The new European SCORE2 estimates the combined risk of fatal and non-fatal cardiovascular (CV) events, in contrast with SCORE's use for CV mortality only. Although controversial, several studies point out that Coronary Artery Calcification (CAC) scoring could improve CV risk stratification in primary prevention.

Purpose

Assess the impact of including CAC score to the new SCORE2 in MACE prediction and CV risk stratification in an asymptomatic Portuguese population.

Methods

The new SCORE2 was calculated in a population-based cohort of 1,014 individuals (mean age 58.6±8.5 years) without known CV disease and diabetes. Population was stratified into three SCORE2 risk categories (low-, moderate- and high-risk). According to the Hoff's nomogram, CAC score was categorized into: low CAC (0≤CAC<100 or P<50); moderate CAC (100≤CAC<400 or P50–75) and high or severe CAC (CAC≥400 or P>75). Kaplan-Meier survival curves were estimated and a multivariate regression analysis predicted the MACE risk for both scores. C-statistic methodology evaluated the ability of CAC when added to the SCORE2 model in MACE prediction.

Results

Kaplan-Meier curves showed that the highest categories of both scores presented a worst survival. Cox regression analysis showed that the highest categories of both CAC and SCORE2 remained in the equation with an increased MACE risk (HR) of 3.69 (p=0.008) and 9.87 (p=0.005), respectively, when compared with the lowest categories. C-statistic demonstrated that the predictive value for MACE increased from 0.668 (SCORE2 model) to 0.787 when CAC was included (p=0.012), showing a better predictive and discriminative capacity for MACE.

Conclusions

Our results highlight the importance of adding CAC score to SCORE2 in primary prevention to improve cardiovascular risk stratification and MACE risk prediction. Larger prospective multicenter cohorts with longer follow-up should reproduce and validate these findings.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM
Development and validation of the HARMS2-AF lifestyle risk score to predict incident AF
Authors: Segan L , Canovas R , Nanayakkara S , Chieng D , Prabhu S , Ling L H , Voskoboinik A , Sugumar H , Lee G , Morton J , Kalman J , Kistler P
Published: October 2022

Background

Lifestyle risk factors (RFs) are a modifiable target in atrial fibrillation (AF) management. However, the relative contribution of individual lifestyle RFs to AF incidence has not been described.

Purpose

Development and validation of a novel AF-lifestyle risk score to determine AF risk in the general population.

Methods

The UK Biobank (UKB) is a large prospective cohort with outcomes measured >10 years. In the UKB, we performed regression analysis of AF lifestyle RFs which were then evaluated in a multivariable model and a weighted score was developed. Next, the risk score was externally validated in the Framingham Heart Study (FHS) population. Kaplan-Meier estimates ascertained the 10-year risk of AF development.

Results

In the UKB, AF incidence was 5.3% among 302,926 participants, with a median time to AF 7.3 years (IQR 4.3–9.8). Hypertension, sleep apnoea, male sex, age, obesity (BMI>30 kg/m2), alcohol and smoking were predictive variables (all p<0.001); physical inactivity (OR 1.02,95% CI 0.97–1.10, p=0.3), diabetes (OR 0.98,95% CI 0.91–1.06, p=0.2) and BMI 27–30 kg/m2 (OR 1.02, 95% CI 0.97–1.07, p=0.424) were not significant. The HARMS2-AF score (Figure 1) had similar predictive performance (AUC=0.782, LogLoss 0.178, Brier Score 0.046) to the unweighted regression model (AUC 0.808) in the UKB. Validation in the FHS (AF incidence 6.7% of 7206 participants) maintained excellent predictive performance with an AUC of 0.747 (95% CI 0.724–0.769, Figure 2). A higher HARMS2-AF score (>5 points) was associated with a heightened 10-year AF risk (score 5–9: OR 9.35, score 10–14: OR 33.34).

Conclusions

The HARMS2-AF score is a novel lifestyle risk score which may help identify individuals at risk of AF and assists in general population screening.

Funding Acknowledgement

Type of funding sources: None.
Have the ESC guidelines improved the identification and prevention of individuals at risk of premature myocardial infarction?
Authors: Zeitouni M , Sulman D , Silvain J , Kerneis M , Guedeney P , Barthelemy O , Procopi N , Collet J P , Montalescot G
Published: October 2022

Background

Over the last 20 years, the proportion of young patients admitted for MI has increased. It is unknown whether the 5-year changes in ESC/EAS guidelines and the new SCORE2 can improve the detection and treatment of individuals at risk of premature MI.

Purpose

To determine how consecutive changes in the ESC/EAS guidelines affected the identification and treatment of young adults premature STEMI.

Methods

Patients admitted for a first STEMI in the ePARIS between 2010 and 2018 were included (n=2757) and stratified by age categories (<55 y-o; 55–65 y-o; >65 y-o). Using baseline characteristics, we evaluated whether patients in each age group would have been detected as high risk and treated with primary prevention statins before their first STEMI based on the 2021 EAS/ESC guidelines versus 2019 and 2016 guidelines (class I, IIA and IIB recommandations). Eligibility for intensive lipid-lowering therapy in secondary prevention according to age was also assessed.

Results

Among the 2757 individuals admitted for a first STEMI, 1253 (45,7%) were <55 y.o, 633 (22.9%) were [55–65] and 871 (31.4%) were >65. Only 17% and 18% of young individuals would have been considered as high risk and eligible for primary prevention statins prior to their first STEMI according to 2016 and 2019 EAS/ESC guidelines respectively, compared with individuals aged 55–65 years (41% and 35%) and >65 years old (21% and 72%), p<0.01. Following 2021 ESC guidelines, 62.5% of individuals aged <55 y.o would have been detected as eligible for primary prevention statins, without difference with individuals aged 55 to 65 years old (61.7%) and >65 y.o (62.1%) (figure). At discharge, based on the expected reduction of baseline LDL-C with maximal dose statins and ezetimibe, 47% of patients with premature STEMI would be eligible for PCSK9i compared with 50% and 37% in individuals aged 55–65 y-o and >65 y-o, respectively.

Conclusions

While 2016 and 2019 ESC guidelines poorly detected young individuals at risk of premature MI, the 2021 ESC guidelines using the new SCORE2 allowed a much better detection of young individuals at risk for a first STEMI. Young patients were also more likely to be eligible for intensive lipid-lowering therapy after their first premature STEMI.

Funding Acknowledgement

Type of funding sources: None.
Plasma hydroxyanthranilic acid as a predictor of stress induced myocardial ischemia in non-obstructive coronary artery disease
Authors: Karaji I , Lonnebakken M T , Storesund S , Khan I , Ueland P M , Vikenes K , Nygard O K , Pedersen E R
Published: October 2022

Background

The tryptophan catabolite hydroxyanthranilic acid (HAA) has potent immunomodulatory and vasoactive effects. HAA is also a precursor in the synthesis of nicotinamide adenine dinucleotide (NAD), a crucial cofactor in energy-metabolism. We have previously demonstrated that elevated plasma HAA predicted risk of myocardial infarction.

Purpose

To explore if plasma HAA is associated with stress induced myocardial ischemia in non-obstructive coronary artery disease (CAD).

Methods

In 132 patients with chest pain and non-obstructive CAD by coronary computed tomography angiography (CCTA), plasma HAA was analyzed by gas chromatography tandem mass spectrometry. All participants underwent myocardial contrast stress echocardiography. Myocardial ischemia was assessed as delayed contrast replenishment at peak dobutamine stress during real-time low mechanical index imaging and destruction replenishment. The extent of ischemia was defined as the number of segments with delayed contrast enhancement using a 17-segment left ventricular model. Associations of plasma HAA with myocardial ischemia was evaluated in a multivariate adjusted linear regression model.

Results

Mean (SD) age at inclusion was 63 (8) years and 56% were women. At CCTA, the median (25th, 75th percentile) coronary artery calcium (CAC) score was 42 (13–107) Agatston units, whereas the mean (SD) segment involvement score (SIS) was 2.6 (1.6). Myocardial ischemia was found in 52% of patients with on average 5 (3) ischemic segments per patient. Serum HAA did not correlate with the CAC score or SIS (p>0.29). After multivariate adjustment including age, sex, body mass index, systolic blood pressure, diabetes, current smoking, and LDL cholesterol, the odds ratio and 95% confidence interval for myocardial ischemia was 1.55 (1.04–2.32), P=0.03, per SD increment of plasma HAA levels (log transformed). Plasma HAA was also associated with the extent of myocardial ischemia with a multivariate adjusted β of 0.26, P=0.004.

Conclusion

Plasma HAA is associated with the extent of myocardial ischemia in non-obstructive CAD. Potential roles of this metabolite in atherogenesis, vascular dysfunction and as a predictor of myocardial ischemia should be further elucidated.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Western Norway Regional Health Authority
The relative importance of particle count, type, and size of ApoB-containing lipoproteins in risk of myocardial infarction
Authors: Morze J , Melloni G E , Rynkiewicz A , Gruchala M , Guasch-Ferre M , Ruff C T , Hu F B , Sabatine M S , Marston N A
Published: October 2022

Background

An accumulating body of evidence suggests that the number of apolipoprotein B-containing particles (ApoB-P) is more predictive of cardiovascular risk than their lipid content. However, it is unclear if this association is consistent across different lipoprotein types and sizes.

Purpose

We aimed to evaluate if particle type and size are associated with incident myocardial infarction (MI) beyond ApoB-P count. Moreover, we aimed to determine if the risk associated with lipoprotein(a) is additive to that of ApoB-P.

Methods

This prospective cohort study included 96,126 participants without prior history of stroke, coronary or peripheral artery disease or use of lipid-lowering medication from the UK Biobank. Count and size of VLDL, IDL, LDL, and HDL, as well as ApoB level and total ApoB-P count were measured in non-fasting plasma samples by nuclear magnetic resonance platform. Lipoprotein(a) was measured by immunoturbidimetric assay. We explored associations between these lipoprotein markers and incident MI using Cox proportional hazard models adjusted sequentially for clinical covariates, HDL count and size, and ApoB-P.

Results

Over a median follow-up of 12.1 years, 1702 participants had incident MI. In unadjusted models, 1-SD increases in ApoB-P count, ratio of VLDL to (LDL+IDL) particle counts, VLDL size and lipoprotein(a) were associated with a higher risk of MI, while LDL size was associated with a lower risk of MI (Table 1). When adjusting for clinical covariates and lipid parameters, only ApoB-P and lipoprotein(a) remained significantly associated with a higher risk of MI (HR: 1.40 [1.32; 1.48] and 1.20 [1.14; 1.27], respectively). Adjusted restricted cubic splines confirmed findings from linear trend Cox models (Figure 1). ApoB-P count was highly correlated with ApoB level (r=0.99), and replication of analyses replacing one for another revealed no change in results.

Conclusion

The risk of MI is independently associated with the total particle count of all ApoB-P, and not the size or type of these lipoproteins. ApoB level can be used as a very accurate surrogate of ApoB-P count in the clinical setting. Lipoprotein(a) is associated with MI risk independently of total particle count, and therefore, the combination of ApoB and lipoprotein(a) may provide the optimal clinical evaluation of lipid-mediated MI risk.

Funding Acknowledgement

Type of funding sources: None.
Investigation of type 1 collagen a1 chain in plasma as a potential novel biomarker for prediction of coronary heart disease
Authors: Hammareus F , Nilsson L , Ong K L , Kristenson M , Festin K , Lundberg A , Chung R W S , Swahn E , Alfredsson J , Holm Nielsen S , Jonasson L
Published: October 2022

Background

Remodeling of the extracellular matrix (ECM) plays a crucial role in development and progression of atherosclerosis. Collagens, in particular type I collagen, are the most abundant ECM proteins in an atherosclerotic plaque. Recently, type I collagen α1 chain (COL1α1) in plasma was identified as a potential predictor of coronary heart disease (CHD).

Aim

The aim was to further confirm the predictive value of COL1α1 and also to investigate its correlates in a population-based cohort as well as changes over time in patients with manifest CHD in Sweden.

Methods

In a total of 1007 well-characterized individuals (50% women), 86 CHD cases and 184 sex- and age-matched controls were identified at 13 years follow-up. CHD at follow-up was defined as first-time event of myocardial infarction (MI) or invasive coronary intervention. Plasma levels of COL1α1 was quantified by the Luminex assay while PRO-C1 and C1M, two markers of type I collagen synthesis and degradation, respectively, were quantified by ELISA. In Cox proportional hazard analysis, log2 values of biomarker levels were used. In addition, temporal change of COL1α1 levels was also examined in a cohort of 125 patients with acute MI followed for 6 months.

Results

COL1α1 levels were significantly associated with incident CHD, both unadjusted (HR = 0.69, 95% CI 0.56–0.87, p=0.001) and after multiple adjustment (HR = 0.55, 95% CI 0.41–0.75, p<0.001). PRO-C1 was similarly associated with CHD, unadjusted (HR = 0.62, 95% CI 0.47–0.82, p=0.001) as well as adjusted (HR = 0.61, 95% CI 0.43–0.86, p=0.005), while C1M was not. In patients with acute MI, COL1α1 levels remained stable over 6 months. COL1α1 was significantly correlated to PRO-C1 (r=0.73, p<0.001), while there were no correlations to C1M, markers of inflammation (C-reactive protein, interleukin-6, matrix metalloproteinase-9) or myocardial injury (troponin T).

Conclusions

Circulating COL1α1 in plasma was independently and inversely associated with incident CHD. Furthermore, COL1α1 levels appeared to be relatively stable after an acute MI. COL1α1 levels seem to reflect collagen synthesis rather than collagen degradation and inflammation. Future studies are needed to confirm whether COL1α1 is a clinically useful marker and/or predictor of CHD.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): This research was in part financed by a grant from the Region of Östergötland, Sweden, aimed towards scientists early in their career. We would like to thank the people behind this grant for contributing to this research.This research was also partly supported by Futurum - the academy for healthcare in Region Jönköping County.