bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma amyloid-beta levels and risk of new-onset atrial fibrillation in the general population
Authors: Lu Z , Tilly M , Wolters F , De Groot N M S , Ikram M A , Kavousi M
Published: October 2022

Background

Atrial fibrillation (AF) is a major health burden worldwide, with significant sex differences in epidemiology and risk factors. Amyloid-β40 (Aβ40) and Amyloid-β42 (Aβ42), the hallmark of cerebral amyloid angiopathy, have recently been linked to prevalence and prognosis of several cardiovascular outcomes including stroke and coronary heart disease. However, whether these biomarkers are associated with incident AF remains largely unknown.

Purpose

To investigate the associations between plasma concentrations of Aβ40 and Aβ42 with new-onset AF.

Methods

4,134 participants without a history of AF at baseline (from 2002 to 2005) with qualified plasma samples in the Rotterdam Study were included in this study. AF was diagnosed by electrocardiograms, general practitioners' and hospital records. Cox proportional hazards regression models with natural cubic splines were used to assess the linear/nonlinear association between biomarkers and risk of new-onset AF. All models were adjusted for traditional cardiovascular risk factors.

Results

Mean age was 71.3±7.2 years and 2,383 (57.6%) were women. Median follow-up time was 9.2 years. In the fully adjusted model, higher levels of Aβ40 [hazard ratio, 95% confidence interval: 1.16 (1.05–1.28)] and Aβ42 [1.19 (1.09–1.31)], as well as Amyloid-β42 to β40 ratio (Aβ42/40) [1.09 (1.02–1.17)] were significantly associated with incident AF. The observed association between Aβ40 and AF attenuated after mutual adjustment for Aβ42 [1.05 (0.92–1.19)]. In addition, a J-shaped association was found between Aβ40 and AF with the lowest AF risk at Aβ40 values of 212.5 pg/ml.

Conclusions

Both Aβ40 and Aβ42 were independently significantly associated with new-onset AF in the general population independent of cardiovascular risk factors. Findings also suggest a stronger association between AF onset and Aβ42 and AF onset, compared to Aβ40. A nonlinear association was found between Aβ40 and AF, reflecting a substantially increased AF risk among participants with severely increased Aβ40 values.

Funding Acknowledgement

Type of funding sources: None.
Decreasing albumin within normal range is associated with increased likelihood of ischemic heart disease
Authors: Coster D , Kodesh A , Fardman A , Tiosano S , Moshkovits Y , Bernstein D , Kaplan A , Shamir R , Maor E
Published: October 2022

Background

Albumin (ALB) is a known biomarker of frailty, and cardiovascular disease and frailty are interdependent. Epidemiological evidence demonstrates that low serum albumin levels are linked to events of ischemic heart disease (IHD), venous thromboembolism, heart failure, atrial fibrillation, and stroke.

Purpose

We aimed to investigate the association of variations in ALB levels that are within normal range with IHD events among apparently healthy adults.

Methods

A case-control retrospective study of self-referred adults participating in an executive screening program between 2002 and 2017. All subjects were free of IHD and diabetes at baseline and had their ALB documented in each visit. Only subjects with at least two ALB measurements and whose ALB levels were within the normal range at all visits were included. Relationships between ALB trend and occurrence of IHD (acute coronary syndrome or percutaneous coronary intervention) within 2 years from the last visit were investigated.

Results

The final study cohort included 16,386 subjects. Median age was 53 (IQR 45–60), 11,461 (70%) were men. Analysis included a total of 99,127 visits. Median number of visits per subject was 5 (IQR 3–9, median inter-visit time 1.02 years) and median ALB level was 4.4 (IQR 4.2–4.6). IHD within 2 years was diagnosed in 545 (3%) subjects. Of those, only 36 were female and they tended to have lower variations in ALB throughout the years. Hence, we conducted an analysis of the 509 males only, and created an equal-size age-matched cohort of IHD-free subjects. Our analysis demonstrated a progressive and significant decrease in ALB levels among IHD cases, but not among controls (mean decrease of 0.021 g/DL vs. 0.004 g/DL per year, p<0.01; OR [CI] = 0.82 [0.72–0.93]; Figure 1). Similar results were found among subjects with at least 3 or 4 visits (0.015 g/DL vs. 0.006 g/DL per year, p=0.027, and 0.009 g/DL vs. 0.003 g/DL per year, p=0.045, respectively).

Conclusions

Kinetics of ALB within the normal range can identify men at risk for IHD in preventive healthcare screening programs.

Funding Acknowledgement

Type of funding sources: None.
Characteristics of patients with lipoprotein(a) assessment: a health insurance claims database analysis
Authors: Stuerzebecher P E , Schorr J , Klebs S , Laufs U
Published: October 2022

Background

Elevated lipoprotein(a) (Lp(a)) is an inherited risk factor for cardiovascular disease. Testing for Lp(a) in primary care is recommended by current ESC guidelines to identify persons at risk. We aimed to report contemporary trends in Lp(a) testing in Germany and subsequent changes in treatment strategies and patient's outcome over time.

Methods and results

An observational, retrospective, anonymized claims data analysis was performed on a database with 4 million patients, representative of the German population in the years 2015 to 2018. Patients were eligible when no Lp(a) test was documented in the year prior to the index date/quarter (time point of the first documented Lp(a) test) and if the patient data was available for at least 1 year before and after the Lp(a) test or until death, whichever came first. In a cross-sectional analysis, Lp(a) test rates in the selected database population increased from 0.25% (n=7,432) in 2015 to 0.34% (n=10,257) in 2018. About 57.8% of the tested population was female. Higher test rates were observed in women especially in younger age groups. A subgroup analysis of patients with previous atherosclerotic cardiovascular disease (ASCVD) revealed overall higher Lp(a) test rates (0.43% in 2015, 0.60% in 2018). In a longitudinal analysis, patients tested for Lp(a) and respective controls matched for age, gender and region, were followed for a maximum of four years. Out of 3,139,410 eligible patients, 36,609 (1.17%) were tested for Lp(a) over the study period at a mean age of 51.91 years and were meeting the inclusion criteria. In comparison to matched controls without Lp(a) test, patients tested for Lp(a) had more comorbidities and higher ASCVD risk. The Lp(a)-tested cohort and the control group had similar mortality rates (0.88 vs. 0.94 per 100 person-years (PY), p=0.21). However, total mortality was lower in patients with prior ASCVD and Lp(a) test compared to matched patients with prior ASCVD but no Lp(a) test (Rates: 2.30 vs. 3.64 per 100 PY, p<0.001). Importantly, the patients with Lp(a) test were treated with a higher number of cardiovascular medications, underwent more laboratory examinations, and had more frequent consultations by specialized physicians after the test.

Conclusion

Lp(a) testing is an indicator of more intensive diagnostic work-up and treatment. Less than 1% of the patients have been newly tested for Lp(a) in 2018. The data identify an opportunity to better characterize ASCVD risk by testing for Lp(a).

Funding Acknowledgement

Type of funding sources: None.
Quantitative cardiovascular magnetic resonance perfusion mapping as a guide for diagnosis
Authors: Androulakis E , Azzu A , Surkova E , Bakula A , Papagkikas P , De Silva R , Kellman P , Pennell D , Alpendurada F
Published: October 2022

Background

There is a lack of gold-standard non-invasive clinical markers derived from quantitative cardiovascular magnetic resonance (CMR) stress perfusion.

Purpose

This study aimed to compare quantification indices testing the hypothesis that they can discriminate possible normal from abnormal groups including microvascular dysfunction (MVD), coronary artery disease (CAD), and non-diagnostic tests due inappropriate response to the stressor agent.

Methods

Four-hundred and thirty-six consecutive patients (n=436, mean age 59.5 yrs) with typical angina and/or risk factors for CAD underwent stress CMR perfusion imaging using a dual-sequence quantitative spiral pulse protocol to estimate quantitative markers on a 1.5 T scanner. Anatomical coronary information, risk factors, and myocardial infarct were evaluated. Myocardial perfusion reserve values (MPR) were adjusted for rate-pressure product. For each perfusion assessment 3 short axis slice locations were imaged per heartbeat over a 60-heartbeat acquisition during an IV bolus of 0.05 mmol/kg of gadolinium contrast. Patients were divided into 4 groups: A) normal perfusion study; B) positive perfusion study due to epicardial coronary artery disease; C) positive perfusion study due to microvascular coronary artery disease; and D) non-diagnostic perfusion study due to inappropriate response to pharmacological stress.

Results

Stress myocardial blood flow (SMBF) and mean adjusted MPR differed between patients with no ischaemia and those clinically diagnosed with MVD (2.41±0.75 vs 1.81±0.52 mL/g/min, p<0.001, 2.78±0.94 vs 2.39±1.02, p=0.009, respectively). Patients deemed to have inadequate hyperaemia as opposed to inducible ischaemia had the lowest mean SBF of 1.25±0.32 vs 1.80±0.61 mL/g/min (p<0.001); a cut-off value of <1.34 mL/g/min had the best predictive diagnostic accuracy for inadequate stress (area under curve [AUC] 0.875). Of note, comparing MVD vs CAD (single, 2-vessels, multivessel disease) without infarction stress pulmonary transit time (PTT) (centroid 6.9±0.72 vs 5.95±0.58, p=0.026), SMBF (1.80 vs 2.10 mL/g/min, p=0.0075), stress endo (1.60 vs 1.94 mL/g/min, p=0.0013), and stress epi (1.94 vs 2.21 mL/g/min, p=0.021) differed significantly between the two groups. The presence of infarction was shown also to be a significant discriminator between the two groups in logistic regression analysis (OR: 8.3, p=0.030).

Conclusions

This study showed fully quantitative stress markers may be useful in discriminating MVD and CAD patients as well as excluding patients with inadequate hyperaemia.

Funding Acknowledgement

Type of funding sources: None.
Carotid ultrasonography improves residual risk stratification in guidelines-defined high cardiovascular risk patients
Authors: Mavraganis G , Georgiopoulos G , Delialis D , Aivalioti E , Patras R , Petropoulos I , Dimopoulou A M , Angelidakis L , Sianis A , Bampatsias D , Dimoula A , Maneta E , Kosmopoulos M , Stellos K , Stamatelopoulos K
Published: October 2022

Background

The clinical value of carotid atherosclerosis markers for residual risk stratification in high atherosclerotic cardiovascular disease (ASCVD) risk patients is not established.

Purpose

In the present study we aimed to derive and validate optimal values of markers of carotid subclinical atherosclerosis improving risk stratification in guidelines-defined high ASCVD risk patients.

Methods

We consecutively analysed high or very high ASCVD risk patients from a cardiovascular (CV) prevention registry (n=751, derivation cohort) and from the Atherosclerosis Risk in Communities (ARIC) study (n=2,897, validation cohort). Baseline ASCVD risk was defined using the 2021 European Society of Cardiology (ESC) guidelines (clinical ESCrisk). Intima-media thickness (IMT) excluding plaque, average maximal (avg.maxWT), maximal wall thickness (maxWT) and number of sites with carotid plaque were assessed. As endpoint of the study was defined the composite of CV death, acute myocardial infarction (MI) and revascularization after a median of 3.4 years in both cohorts and additionally for 16.7 years in the ARIC cohort.

Results

MaxWT >2.00mm and avg.maxWT >1.39mm provided incremental prognostic value, improved discrimination and correctly reclassified risk over the clinical ESCrisk both in the derivation and the validation cohort (p<0.05 for net reclassification index, integrated discrimination index and Delta Harrell's C index). MaxWT <0.9mm predicted very low probability of CV events (negative predictive value = 97% and 92% in the derivation and validation cohort, respectively). These findings were additionally confirmed for very long-term events in the validation cohort.

Conclusion

Integration of carotid ultrasonography in guidelines-defined risk stratification may identify very high risk patients in need for further residual risk reduction or at very low probability

Funding Acknowledgement

Type of funding sources: None.
Effects of canagliflozin on cardiovascular and kidney outcomes and mortality in primary and secondary cardiovascular prevention: pooled analysis from the CANVAS program and CREDENCE trial
Authors: Ang F , Rapattoni W , Bajaj H S , Mancini G B J , Poirier P , Sharma A , Wong N C , Slee A , Levin A , Mahaffey K W
Published: October 2022

Background/Introduction

Individuals with type 2 diabetes mellitus (T2DM) are at a greater risk for experiencing cardiovascular (CV) and kidney events. Canagliflozin is a sodium glucose co-transporter 2 inhibitor that has demonstrated reduction of these events in participants with T2DM with or without a history of CV disease (CVD) in both the CANVAS Program and CREDENCE trial.

Purpose

To determine the pooled effects of canagliflozin on CV outcomes, kidney outcomes, and all-cause mortality in trial participants with and without a history of CVD (secondary and primary prevention, respectively).

Methods

This post hoc analysis pooled individual participant data from the CANVAS Program and CREDENCE trial. The effects of canagliflozin versus placebo on time to first event for CV outcomes (major adverse cardiovascular events [MACE], which was defined as CV death, myocardial infarction [MI] or stroke; CV death; hospitalization for heart failure [HHF], and the composite of CV death or HHF), kidney outcomes (end-stage kidney disease [ESKD], doubling of serum creatinine [dSCr], and the composite of ESKD or dSCr), and all-cause mortality were assessed in participants with T2DM with or without a history of CVD.

Results

Among the 14,543 participants from the pooled CANVAS Program (N=10,142) and CREDENCE trial (N=4401), 5667 (39%; canagliflozin, n=3128; placebo, n=2539) were in the primary prevention group and 8876 (61%; canagliflozin, n=4869; placebo, n=4007) were in the secondary prevention group. Baseline characteristics of participants in each group were generally similar. Across both primary and secondary prevention participants, no heterogeneity in the relative risk reduction of CV outcomes, kidney outcomes, and all-cause mortality with canagliflozin versus placebo was observed (all P interaction >0.624; Figures 1 and 2). The benefits of canagliflozin on MACE and the composite of CV death or HHF were observed as early as 6 months into treatment in both subgroups of participants and were sustained throughout the study.

Conclusions

In this pooled analysis of patient-level data from the CANVAS Program and CREDENCE trial, treatment with canagliflozin demonstrated early benefits and was associated with reduced risk of CV outcomes, kidney outcomes, and all-cause mortality, with similar results across primary and secondary prevention participants with T2DM.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Janssen, Inc.
Right ventricular function and outcome in patients undergoing transcatheter mitral valve repair
Authors: Koschutnik M , Dona C , Nitsche C , Dannenberg V , Koschatko S , Mascherbauer K , Beitzke D , Loewe C , Huelsmann M , Schneider M , Bartko P , Goliasch G , Hengstenberg C , Kammerlander A , Mascherbauer J
Published: October 2022

Objectives

This study sought to assess the impact of right ventricular dysfunction (RVD) on event-free survival after transcatheter mitral valve repair (TMVR) for severe mitral regurgitation.

Background

The prognostic value of left and RV global longitudinal strain (LV- and RV-GLS) on cardiovascular magnetic resonance feature tracking (CMR-FT) in patients undergoing TMVR is unknown.

Methods

Consecutive TMVR patients underwent pre-procedural and follow-up CMR-FT analysis. Kaplan-Meier estimates and multivariable Cox-regression analyses were performed, using a composite endpoint of heart failure hospitalization (HFH) and death.

Results

62 patients (78.3±7.0y/o, 45% female, EuroSCORE-II: 9.6±7.1%) underwent CMR-FT prior to TMVR, 24% had concomitant tricuspid edge-to-edge repair (TTVR). On presentation, 23 (37%) patients suffered RVD, defined as RV-GLS >−20% on CMR-FT. RVD was associated with reduced LV and RV ejection fraction (LVEF: 39.2 vs. 48.7%, p=0.008, RVEF: 35.1 vs. 46.7%, p<0.001), as well as impaired LV-GLS (−14.0 vs. −19.5%, p=0.012).

Eighteen events (12 deaths, 6 HFH) occurred during follow-up (11.4±9.1 months). On multivariable Cox-regression adjusted for baseline, procedural, imaging, and biomarker data, RV but not LV-GLS was significantly associated with outcome (adj.HR 2.50, 95% CI: 1.29–4.86, p=0.007 and 1.46, 95% CI: 0.50–4.28, p=0.491, respectively). Among various definitions of RVD on echocardiography and CMR, only RV-GLS on CMR-FT was significantly associated with outcome (RV-GLS >−20%: adj.HR 7.53, 95% CI: 2.07–27.42, p=0.002), but not RVEF on CMR or echo-indices of RV function (Central Illustration).

Follow-up CMR-FT was performed in 21 (34%) patients and RV-GLS significantly improved after TMVR (−20.6 to −25.2%, p=0.016), irrespective of additional TTVR.

Conclusions

RV-GLS, as determined on CMR-FT, rather than LV-GLS or RVEF, is an independent predictor of outcome in patients undergoing TMVR.

Funding Acknowledgement

Type of funding sources: None.
Elevated levels of Lp(a) are associated with coronary lesion complexity in patients hospitalized for an acute myocardial infarction: data from the French RICO Survey
Authors: Kouame I , Farnier M , Chague F , Maza M , Bichat F , Zeller M , Cottin Y
Published: October 2022

Background

Although patients with elevated Lp(a) are at high risk of acute myocardial infarction (MI), coronary artery disease (CAD) burden associated with Lp(a) remains poorly investigated.

Methods

Single center study including all consecutive patients hospitalized for an acute MI in Coronary Care Unit from the RICO database (2019–2021) who underwent coronary angiography and blood sample for Lp(a) assessment on admission. Coronary lesion complexity was retrospectively assessed by SYNTAX score and pre-specified angiographic criteria. Patients were compared according to their Lp(a) levels: <50 mg/dL (normal), ≥50 mg/dL and ≤100 mg/dL (high) and >100 mg/dL (very high).

Results

921 patients were included, of whom 177 (19.2%) had elevated Lp(a) >50 mg/dL, including 121 (13.1%) with high and 56 (6.1%) with very high Lp(a). Median (IQR) age was similar across the 3 groups (normal: 68 (58–78)y; high: 70 (60–80)y; very high: 69 (61–78)y, p=0.381). When compared with patients with normal Lp(a), patients with high and very high Lp(a) levels had increased prevalence of personal history of CAD (19%, 28% and 29%, respectively, p=0.026) and family history of CAD (19%, 26% and 29%, p=0.032, respectively). The rate of women was more common in very high Lp(a) level than in high and normal groups (46%, 33%, and 29%, respectively, p=0.016). Rate of ST-segment elevation MI was similar for the 3 groups (p=0.961). At coronary angiography, CAD burden, as assessed by SYNTAX score was much higher in elevated Lp(a) groups (11 (6–19), 15 (8–24), 17 (7–25), p=0.001, respectively). Moreover, patients with elevated Lp(a) had more complex coronary lesions (p=0.034), characterized by left main (p=0.021), and calcified lesions (p=0.002) (figure). In-hospital mortality gradually increased across the 3 groups (2.8%, 6.6%, 8.9%, p=0.010, respectively).

Conclusions

This retrospective study in patients with acute MI shows that elevated Lp(a) were common, associated with high risk for in-hospital mortality. Patients with high Lp(a) were characterized by severe CAD burden, with complex anatomy features including left main and calcified lesions. The long-term prognostic impact of Lp(a)-associated CAD burden needs to be explored.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): ARS Bourgogne Franche ComtéCHU Dijon BourgogneAssociation de Cardiologie de Bourgogne
Awareness of lipid guideline recommendations for high-risk patients amongst primary care physicians in Canada
Authors: Gupta M , Padarath M , Prest L , Naik N , Hegele R
Published: October 2022

Background

Lipid guidelines for cardiovascular (CV) risk reduction have evolved in recent years, particularly since the introduction of PCSK9 inhibitors. In many jurisdictions, CV risk management is provided by primary care physicians (PCPs). We surveyed Canadian PCPs regarding their awareness and implementation of the 2021 Canadian Cardiovascular Society (CCS) lipid guideline recommendations for patients following an acute coronary syndrome (ACS) or for those with diabetes but without CV disease.

Methods and results

From a national database of PCPs with interest and/or experience in CV medicine, we invited PCPs to complete a survey regarding lipid management in high-risk patients. A committee of PCPs and specialists with lipid expertise including several co-authors of the 2021 CCS lipid guidelines had designed the survey to probe awareness and practice patterns. A total of 203 PCPs from across Canada completed the survey between January and March 2022. 23.6% of respondents had previously prescribed a PCSK9 inhibitor. Almost all (96.5%) PCPs concurred that a post-ACS patient should be seen by their PCP within 4 weeks of hospital discharge (79.3% within 2 weeks). Almost half (45.3%) responded that discharge summaries provided inadequate information relevant for PCPs, and 43% felt that lipid management post-ACS was the primary responsibility of specialists. More than half (56%) articulated challenges when seeing a post-ACS patient, related to inadequate discharge information, complexities of polypharmacy and duration of therapies, and managing perceived or real statin intolerance. 62% correctly identified the LDL-C intensification threshold of 1.8 mmol/L in post-ACS patients, while 79% considered that PCSK9 inhibitors were indicated only for those patients who were already receiving statins plus ezetimibe or had substantially elevated LDL-C levels. 55.2% were able to correctly identify clinical features associated with greatest absolute benefit of PCSK9 inhibitors in post-ACS patients. For patients with diabetes but without ASCVD, 80% of PCPs incorrectly believed that PCSK9 inhibitors were indicated for LDL-C levels above threshold despite statin therapy, and only 42% correctly identified the LDL-C threshold for treatment intensification of 2.0 mmol/L.

Conclusion

While PCPs are aware of the urgency regarding lipid management in post-ACS patients, many encounter challenges after hospital discharge, frequently deferring lipid management to specialists. Thus, almost one year following publication of the 2021 CCS lipid guidelines, substantial knowledge gaps remain regarding intensification thresholds and treatment options for patients post-ACS or for those with diabetes. Innovative and effective knowledge translation programs are urgently required.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Amgen Canada
The value of T1 mapping in patients with chronic mitral regurgitation
Authors: Riebel Badau C I , Agoston Coldea L
Published: October 2022

Introduction

The management of asymptomatic patients with severe mitral regurgitation (MR) and normal left ventricular (LV) ejection fraction (EF) remains controversial. Progressive fibrosis secondary to volume overload may explain irreversible LV dysfunction post mitral valve surgery, even in patients in which the current guidelines for intervention are applied.

Considering the limitation of the LV EF as a measurement of systolic function, cardiac magnetic resonance emerges as a new technique that can detect and quantify left ventricular fibrosis before irreversible decline in LV function occurs.

Late gadolinium enhancement (LGE) is a recognised method of assessing replacement fibrosis. Native T1 and post contrast administration T1 mapping provide a useful tool for measuring extracellular volume (ECV) – a marker of interstitial fibrosis.

The purpose of this study was to assess the presence of myocardial fibrosis by LGE and T1 mapping in patients with moderate and severe mitral regurgitation and normal ejection fraction.

Method

The study group consisted of 128 consecutive patients with moderate and severe mitral regurgitation with no indication of surgery, compared with a control group of 120 patients with mild MR, studied between 2018 and 2021. Patients with contraindications to CMR were excluded. Electrocardiogram, transthoracic echocardiography and cardiac magnetic resonance, including LGE and T1 mapping were performed in all patients. Circle CVi 42 was used for image post processing and ECV calculation. Statistical analysis was performed with SPPSS 21.0. A p value <0.05 was considered statistically significant.

Results

37 patients with MR presented with different nonischemic patterns of LGE versus 8 controls. Precontrast administration T1 mapping showed significantly higher global T1 time in patients with MR (1178±129 ms) versus controls (974±115). Mean ECV was significantly higher in patients with MR versus controls (36% vs 22%). A comparison between patients with moderate and severe MR revealed significantly higher T1 values and ECV in patients with severe MR despite normal LV EF. During the followup 15 patients required intervention.

Conclusion

Our study has shown that patients with moderate and severe MR that do not meet the current guidelines criteria for surgery have significantly higher T1 times and ECV compared with those with mild MR. The assessment of interstitial fibrosis using CMR T1 mapping techniques may provide an important tool in selecting patients who may benefit from early surgery before irreversible myocardial fibrotic changes occur, thus improving long term prognosis.

Funding Acknowledgement

Type of funding sources: None.
Effects of smoking cessation on the risk of cardiovascular disease: a nationwide population-based study
Authors: Cho J H , Shin S Y
Published: October 2022

Introduction

Cardiovascular disease (CVD) is the global leading cause of death, and the economic and social burden of CVD is still increasing, Smoking is one of the top three leading risk factors for the disease and one of the well-established and important modifiable risk factors for CVD. However, the time course of CVD risk after smoking cessation is unclear.

Purpose

We assess the association between smoking and CVD and the incidence of CVD with years quitting smoking.

Methods

This study used the Korean National Health Insurance Service (NHIS) database. Self-reported smoking habit data were used to classify participants as current, former or never smokers and to investigate the duration and intensity of smoking. Smoking records of participants were updated every 2 years, and all participants whose smoking records were changed or unclear were excluded. The primary outcome was the development of CVD, including myocardial infarction, stroke, heart failure, and cardiovascular death.

Results

Total 5,391,231 participants (953,756 subjects were current smokers, 104,604 subjects were former smokers, 4,432,871 subjects never smoker) were followed-up for an average of 4.2 years. The mean age was 45.8 years, 39.9% were male. Cumulative pack-year (PY) were 14 in current smoker, 10.5 in former smokers at baseline. The median years of quitting smoking for former smoker was 4.

Regardless of whether smoking continues or not, a dose-dependent relationship exists between smoking and CVD (Fig. 1). For those smoked less than 8PY, smoking cessation significantly lowered the CVD risk within 10 years compared to current smokers, and the CVD risk was not significantly different from never smokers (Fig. 2A). However, in the case of smokers over 8PY, although smoking cessation affects the reduction of CVD, the CVD risk decreases slowly over decades, and it takes more than 20 years for the effect of smoking on the CVD risk to disappear (Fig. 2B).

Conclusion

Smoking and CVD have a dose-dependent relationship, and mild smokers with less than 8PY had a similar CVD risk to never smokers when quitting smoking. However, for heavy smokers over 8PY, it takes a long time for the CVD risk from smoking to disappear

Funding Acknowledgement

Type of funding sources: None.
Capability of CT aortic regurgitant orifice to predict aortic regurgitation severity with cardiovascular magnetic resonance as reference
Authors: Martin L Descalzo M D , David Vilades Medel M D , Abdier Vizcarra Tellez M D , Juan Fernandez Martinez M D , Sandra Pujadas Olano M D , Abdel Hakim Moustafa M D , Lidia Bos Real M D , Jose Alberto Hidalgo Perez M D , Ruben Leta Petracca M D
Published: October 2022

Background

Regurgitant orifice area (ROA) measurements by cardiac CT have not been extensively compared with a quantitative classification of aortic regurgitation (AR) severity based on regurgitant fraction (RF) by phase-contrast cardiovascular magnetic resonance (PC-CMR) [1–3].

Purpose

To evaluate ROA diagnostic accuracy by 256-slice CT for predicting severe AR with PC-CMR as reference.

Material and methods

We consecutively enrolled 57 patients with AR prior to surgery assessed by echocardiography, PC-CRM, and CT. Mean age 67.3±15.3 (84% males). Cardiac CT data sets were reconstructed at 75–78% of the R-R interval to measure ROA. According to previous data (4), a cut-off value of 33% by PC-CMR defined severe AR. Receiver operating curve (ROC) were calculated to detect the best CT-ROA cut-off to predict severe AR by CMR.

Results

There were no differences between both groups of AR patients in terms of age, gender, or anthropometric measures. CT-ROA was significantly smaller in patients with RF<33% by PC-CMR (0.24±0.09 vs 0.49±0.22; p<0.001). AR etiology, jet eccentricity, ascending aorta diameters and ejection fraction (LVEF) also were not significantly different according to AR-RF group (Table 1).

CT-ROA significantly correlated with the RF>33% by PC-CMR (Pearson's correlation coefficient (R)=0,48, p<0.001) (Figure 1A).

In the ROC curve analysis to predict significant RF, a CT-ROA cut-off of 0.27 cm2 correctly classified 93% of patients with sensitivity of 97.6% (CI95%:87,7–99,6); specificity of 73.33% (CI95%:48–89); PPV 95,3% (CI95%: 84,5–98,7); NPV 91,7% (CI95%: 64,6% a 98,5%) and area under the curve (AUC) of 0.93 (CI95%: 0.85–1.00; p<0.001) (Figure 1B).

Conclusion

CT-RAO could be useful to distinguish AR severity determined by PC-CMR with a cut-off value of 0.27 cm2 as best predictor.

Funding Acknowledgement

Type of funding sources: None.
Residual inflammatory risk appeared related to weight, atherogenic lipid profile and biomarkers of inflammation, but not to glycaemic control in type 1 diabetes
Authors: J Johansen N , Dejgaard T F , Lund A , Moeller H J , Forman J , Vilsboell T , Andersen H U , Knop F K
Published: October 2022

Background

Mortality associated with atherosclerotic cardiovascular disease reduces average life expectancy by more than a decade in type 1 diabetes. Systemic inflammation drives atherosclerosis, and the concept of residual inflammatory risk (defined by high-sensitivity C-reactive protein (hsCRP) ≥2 mg/l) poses a potential, new therapeutic target for lowering residual cardiovascular risk in type 1 diabetes. However, the characteristics of individuals with residual inflammatory risk in type 1 diabetes are unknown.

Purpose

Identify differences in relevant demographics, clinical and paraclinical parameters for individuals with residual inflammatory risk as compared to those without in type 1 diabetes.

Methods

Baseline characteristics as stratified for CRP ≥2 mg/l were analysed in 105 patients with type 1 diabetes participating in a previously published clinical trial. The study population was sampled to represent the broad background population struggling with glycaemic control and with a high cardiovascular risk.

Results

Residual inflammatory risk was seen in 39.1% of the study population. Compared to individuals without residual inflammatory risk, individuals with residual inflammatory risk were more frequently women, had increased body weight, body mass index and dual-energy X-ray absorptiometry (DXA)-assessed fat mass and exhibited elevated levels of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and total cholesterol as well as triglycerides, interleukin 6 and tumour necrosis factor alpha (Table 1). Glycated haemoglobin, blood pressure and markers of renal function were similar between groups (Table 1).

Conclusion

In the present cohort of individuals with type 1 diabetes, residual inflammatory risk was seen in 39.1% (similar to what is observed outside of type 1 diabetes) and appeared related to overweight/obesity, an atherogenic lipid profile and circulating biomarkers of inflammation but not to glycaemic control, blood pressure or renal function.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): AstraZenecaHerlev Gentofte Hospital
Measures of insulin resistance as a screening tool for dysglycaemia in patients with coronary artery disease. A report from the EUROASPIRE V population
Authors: Ferrannini G , De Bacquer D , Erlund I , Gyberg V , Kotseva K , Mellbin L , Norhammar A , Schnell O , Tuomilehto J , Vihervaara T , Wood D , Ryden L
Published: October 2022

Background

The optimal screening strategy for dysglycaemia, including type 2 diabetes (T2DM) and impaired glucose tolerance (IGT), in patients with coronary artery disease (CAD) is debated.

Purpose

We tested the hypothesis that measures of insulin resistance by homeostasis model assessment (HOMA) indexes may constitute accurate screening methods in a CAD population.

Methods

Insulin, C-peptide, glycated haemoglobin A1c (HbA1c) and an oral glucose tolerance test (OGTT) were centrally assessed in 3534 CAD patients without known dysglycaemia from the EUROASPIRE V survey. Three different HOMA indexes were calculated: HOMA-IR, HOMA2 based on insulin (HOMA2-ins), and HOMA2 based on C-peptide (HOMA2-Cpep). Dysglycaemia was diagnosed based on the two-hour postload glucose (2hPG) value obtained from the OGTT. Information on study participants was obtained by standardised visits. The optimal thresholds of the three HOMA indexes for dysglycaemia diagnosis were obtained by the maximum value of Youden's J statistic on receiver operator characteristics curves. The diagnostic performance of such thresholds was tested for both T2DM (i.e. in reference to a 2hPG value ≥11 mmol/L) and dysglycaemia (i.e. in reference to 2hPG value ≥7.8 mmol/L) and their correlation with several clinical parameters was assessed by Spearman's coefficients.

Results

The mean age of the patients was 63 years and 25% were women. Fifty-four percent of the patients had central obesity, 18% were current smokers, mean blood pressure was 133/80 mmHg and mean LDL-cholesterol 2.4 mmol/L. The OGTT revealed that 41% were dysglycaemic (IGT = 24% and T2DM = 16%). Mean insulin, C-peptide and HOMA indexes were significantly higher in patients with vs. without newly detected dysglycaemia (all p<0.0001). Sensitivity and specificity of the three HOMA indexes for the diagnosis of dysglycaemia were low and the associations between 2hPG and the other parameters in the total sample were weak, with Spearman correlation coefficients of 0.15 for fasting insulin, 0.19 for C-peptide, 0.24 for HOMA-IR, 0.18 for HOMA2-ins and 0.22 for HOMA2-Cpep. HOMA-IR, HOMA2-ins and C-peptide were strongly correlated with body mass index and waist circumference (Spearman correlation coefficients ranging 0.43–0.47).

Conclusion

Screening for dysglycaemia in CAD patients by insulin, C-peptide, HOMA-IR, HOMA2-ins and HOMA2-Cpep had insufficient diagnostic performance to detect dysglycaemia with reference to the yield of an OGTT, which should still be prioritized. Further studies are warranted to assess whether measures of insulin resistance might be better markers of unfavourable metabolic derangement beyond dysglycaemia.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): European Society of CardiologyErling-Perssons Stiftelse
Endothelial dysfunction due to decreased nitric oxide bioavailability in dysglycaemic subjects and first-degree relatives of type 2 diabetic patients
Authors: Ikonomidis I , Pavlidis G , Tsoumani M , Kousathana F , Katogiannis K , Tsilivarakis D , Thymis J , Kountouri A , Korakas E , Pliouta L , Parissis J , Bamias A , Filippatos G , Andreadou I , Lambadiari V
Published: October 2022

Background/Introduction

Oxidative stress plays an important role in the pathogenesis of type 2 diabetes mellitus.

Purpose

We aimed to investigate oxidative stress and nitrites/nitrates concentrations at baseline and during postprandial hyperglycaemia in 40 first-degree relatives (FDR) of type 2 diabetic patients with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic).

Methods

Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5–25μm (Microscan, Glycocheck), a marker of endothelial glycocalyx integrity, coronary flow reserve (CFR) in the distal left anterior descending coronary artery, left ventricular global longitudinal strain (GLS), malondialdehyde (MDA), protein carbonyls (PC) and nitrites/nitrates plasma levels were assessed at 0 and 120 min of a 2-hour OGTT. Insulin sensitivity was evaluated using Matsuda and insulin sensitivity index (ISI).

Results

In all subjects, there were no significant changes in MDA and PC at 120 min after OGTT (p>0.05). Compared with normoglycaemic subjects, in FDR and dysglycaemic subjects, nitrites/nitrates levels were significantly decreased at 120 min (−24% versus −30% versus −3%, respectively) with a parallel increase in PBR (+7% versus +10% versus −3%) and a reduction in CFR (−11% versus −14% versus −6%) and GLS (−4% versus −4% versus +0.1%) (p<0.05 for all comparisons). The percent reduction of nitrites/nitrates levels was associated with abnormal values of Matsuda and ISI, reversely related with the percent increase of PBR (r=−0.60, p=0.001) and positively related with the percent decrease of CFR (r=0.39, p=0.038) and GLS (r=0.48, p=0.008).

Conclusion

Insulin resistance determines acute endothelial responses during OGTT leading to reduced nitric oxide production with resultant coronary and myocardial dysfunction in FDR and dysglycaemic subjects.

Funding Acknowledgement

Type of funding sources: None.
In patients with type 2 diabetes chronic kidney disease is a modifiable cardiovascular risk factor
Authors: Agarwal R , Pitt B , Rossing P , Anker S D , Filippatos G , Ruilope L M , Kovesdy C P , Tuttle K , Vaduganathan M , Wanner C , Bansilal S , Gebel M , Joseph A , Lawatscheck R , Bakris G
Published: October 2022

Background/Introduction

Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is associated with an increased risk of cardiovascular (CV) events. The modifiability of CKD-associated CV risk in patients with T2D across a spectrum of CKD stages remains unknown.

Purpose

To test whether CKD, as defined jointly by estimated glomerular filtration rate (eGFR) and albuminuria (urine albumin-to-creatinine ratio [UACR]), is a modifiable CV risk factor in patients with T2D. Furthermore, to estimate the population-wide reduction in first CV events in the US if all eligible patients were treated with finerenone.

Methods

We estimated the incidence rates of CV events (composite of CV death, non-fatal stroke, non-fatal myocardial infarction, or hospitalisation for heart failure) over a median follow-up of 3.0 years in 13,026 patients with CKD and T2D, treated with finerenone or placebo, in a joint analysis by eGFR and UACR categories. Patients were from FIDELITY, a prespecified pooled analysis of two phase III trials, and had an eGFR ≥25 ml/min/1.73 m2 and UACR 30–5000 mg/g at screening.The potential impact of finerenone treatment on the US population was evaluated by simulating the number of first CV events that could be prevented per year with finerenone, using incidence rates from FIDELITY and prevalence rates of CKD in patients with T2D from the National Health and Nutrition Examination Survey (NHANES).

Results

Lower eGFR and higher UACR categories were associated with higher incidences of CV events in finerenone and placebo recipients (Figure). Finerenone reduced CV risk versus placebo (hazard ratio 0.86; 95% CI 0.78–0.95; p=0.0018) without evidence of moderation of risk reduction by combined eGFR and UACR categories (p interaction = 0.66; Figure 1). Using NHANES, a total of 6.4 million treatment-eligible individuals with CKD and T2D were identified; 75% had CKD with an eGFR ≥60 ml/min/1.73 m2 and 25% had CKD with an eGFR <60 ml/min/1.73 m2. Simulations using this NHANES population projected that 1 year of finerenone treatment could prevent 38,359 CV events in US patients with CKD and T2D, with 66% of events prevented in patients with eGFR ≥60 ml/min/1.73 m2.

Conclusions

Higher albuminuria and lower eGFR are associated with increased CV risk in patients with T2D. Across a range of eGFR and albuminuria categories, CV risk is modifiable. Therefore, CKD is a modifiable CV risk factor in part mediated by mineralocorticoid receptor overactivation. UACR screening to identify patients with T2D and albuminuria with an eGFR ≥60 ml/min/1.73 m2 is likely to provide a significant opportunity for population benefits.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Bayer AG
COVID-19 and the autonomic nervous system
Authors: Xuereb R A , Xuereb R G , Barbara C , Fava S , Magri C J
Published: October 2022

Background

COVID-19 infection has been shown to have an adverse impact on the cardiovascular system. Cardiac injury, as indicated by elevated cardiac troponin and NT-proBNP levels have been confirmed in COVID-19 cases. There is still ambivalent data on the effect of left ventricular function. Cases of left ventricular impairment, persistent hypotension, acute myopericarditis, myocarditis, arrhythmia and heart failure have been reported in the short term, but there is a significant lacuna when it comes to medium and long-term follow-up of subjects previously infected with COVID-19.

Purpose

To assess any residual myocardial and autonomic injury in subjects previously infected with COVID-19 at a median follow-up of 5 months.

Methods

A case-control study was performed. Cases were randomly selected subjects who were previously diagnosed with COVID-19 infection following nasopharyngeal swabbing. Controls were subjects who had not been found to be infected with COVID-19 following swabbing and were negative for COVID-19 IgG antibodies. All participants were submitted a standardised questionnaire regarding past medical history. Blood investigations were taken including NT-proBNP and troponin I levels. In addition, all participants underwent 24-hour ambulatory blood pressure monitoring (ABPM) and 24-hour ECG monitoring. The latter was used to assess both for underlying arrhythmias as well as heart rate variability (HRV), a measure of autonomic regulation of the heart. All data was analysed using SPSS version 23.0.

Results

The study comprised 259 subjects, whereby cases included 174 participants while 75 subjects were age- and gender-matched controls. The study cohort was relatively young with a mean age of 46.1±13.8 years. The median follow-up was of approximately 5 months (median 173.5 days, IQR 129–193.25 days). There was no statistically significant difference between cases and controls with regards cardiovascular risk factors and underlying medical conditions. Likewise, there was no difference in blood investigations, including troponin I and NT-proBNP levels at 5-months follow-up. No difference was noted between the two groups in both awake and asleep blood pressure (BP) readings, as well as dipping BP status. No significant arrhythmias were noted in both groups on 24-hour ECG monitoring. However, when assessing for heart rate variability, it was shown that subjects who had been previously infected with COVID-19 exhibited lower root-mean square differences of successive R-R intervals (RMSSD), p=0.028. This indicates poor vagus nerve-mediated autonomic control of the heart.

Conclusion

Subjects previously infected with COVID-19 exhibited lower HRV as exhibited by low RMSSD as compared to controls. Reduced HRV is a known biomarker for mortality and sudden death in cardiac disease. The possible long-term implications of reduced HRV in subjects previously infected with COVID-19 merits further investigation.

Funding Acknowledgement

Type of funding sources: None.
Serum magnesium is associated with long-term survival of non-ST-elevation myocardial infarction patients
Authors: Shechter M , Cohen H , Sharon A , Koren-Morag N , Grossman E , Maor E
Published: October 2022

Background

In Israel, the rate of drinking water from desalinated sea water has increased dramatically to 60% in the last two decades. However, desalinated water lacks magnesium. Hypomagnesemia is associated with adverse cardiovascular outcome.

Aim

To investigate the association of admission serum magnesium levels (sMg) with long-term survival of non-ST-elevation myocardial infarction (NSTEMI) patients in the light of increased use of desalinated sea water.

Methods

A single-center, retrospective cohort of consecutive petients who were hospitalized with NSTEMI as their primary clinical diagnosis between August 1, 2008 to March 31, 2021. Multivariate Cox regression model was applied for mortality risk.

Results

Study population included 5,675 NSTEMI patients with a mean age of 71±13 years (range 25 to 110), of whom 3,820 (67%) were males. Mean and median sMg levels were 2.0±0.2 (0.5–6.8), 2.0 mg/dL, respectively. During mean follow-up of 4.1±2.9 years (0–14), 2,238 (39%) patients died. Mortality rate was u-shaped when associated with sMg levels (Figure 1) and the study cohort was divided into quintiles according to the sMg levels (≤1.80; 1.81–1.94; 1.95–2.00; 2.01–2.20; ≥2.21). Patients in the highest compared to the lowest sMg quintiles had significantly higher incidence of renal dysfunction with lower eGRF EPI (62±32 vs 76±26 ml/min/1.73 m2, p<0.001) and lower fasting serum glucose (102±37 vs 115±46 mg/dL, p<0.001). All-cause mortality rate was the highest in the lowest and highest sMg quintiles (48%, 33%, 32%, 33% 54%, respectively, p<0.00). Compared to the 2nd sMg quintile (1.81–1.94 mg/dL), with the lowest mortality risk, the lower sMg quintile was associated with a significant and indpendent 24% increased risk of death in a multivariate model (95% CI 1.07–1.44, p<0.001), while the highest quintile was associated with 48% increased risk (95% CI 1.25–1.74, p<0.01) (Figure 2).

Conclusion

Admission low sMg is associated with long-term all-cause mortality in NSTEMI patients. Additionally, long-term mortality is also high in NSTEMI patients with renal dysfunction-induced high sMg levels.

Funding Acknowledgement

Type of funding sources: None.