The association of lipoprotein(a) and coronary artery calcium in asymptomatic patients: a systematic review and meta-analysis.

AIMS: Lipoprotein(a) [Lp(a)] is an atherogenic lipid particle associated with increased risk for coronary heart disease (CHD) events. Coronary artery calcium (CAC) score is a tool to diagnose subclinical atherosclerosis and guide clinical decision-making for primary prevention of CHD. Studies show conflicting results concerning the relationship between Lp(a) and CAC in asymptomatic populations. We conducted a meta-analysis to evaluate the association of Lp(a) and CAC in asymptomatic patients. METHODS AND RESULTS: We systematically searched PubMed, Embase, and Cochrane until April 2023 for studies evaluating the association between Lp(a) and CAC in asymptomatic patients. We evaluated CAC > 0 Agatston units, and CAC ≥ 100. Lp(a) was analysed as a continuous or dichotomous variable. We assessed the association between Lp(a) and CAC with pooled odds ratios (OR) adopting a random-effects model. A total of 23 105 patients from 18 studies were included in the meta-analysis with a mean age of 55.9 years, 46.4% female. Elevated Lp(a) increased the odds of CAC > 0 [OR 1.31; 95% confidence intervals (CI) 1.05-1.64; P = 0.02], CAC ≥100 (OR 1.29; 95% CI 1.01-1.65; P = 0.04; ), and CAC progression (OR 1.43; 95% CI 1.20-1.70; P < 0.01; ). For each increment of 1 mg/dL in Lp(a) there was a 1% in the odds of CAC > 0 (OR 1.01; 95% CI 1.01-1.01; P < 0.01). CONCLUSION: Our findings of this meta-analysis suggest that Lp(a) is positively associated with a higher likelihood of CAC. Higher Lp(a) levels increased the odds of CAC >0. These data support the concept that Lp(a) is atherogenic, although with high heterogeneity and a low level of certainty. PROTOCOL REGISTRATION: CRD42023422034. KEY FINDINGS: Asymptomatic patients with elevated Lp(a) had 31% higher chances of having any coronary calcification (CAC > 0) and 29% higher chances of having more advanced calcification (CAC > 100). It increased the chances of having progression of coronary calcification over time by 43%. For each 1 mg/dL of Lp(a) there was an increment of 1% chance of having coronary calcification.

We conducted a meta-analysis to evaluate the association between Lp(a) and coronary calcification in asymptomatic patients without a known history of coronary artery disease.

Combined Computed Tomography Angiography-Computed Tomography Perfusion in the Identification and Prognostic Assessment of Myocardial Bridging from the CORE320 Study: 5-Year Follow-Up.

Our objective is to use computed tomography angiography (CTA) and computed tomography perfusion (CTP) to identify the ischemic significance of myocardial bridging (MB). We also seek to determine the long-term prognostication of MB in the presence or absence of obstructive coronary artery disease (CAD). The CORE320, a prospective, multicenter study including 381 patients with known or suspected CAD clinically referred for invasive coronary angiography who underwent combined (CTA-CTP) and single-photon emission computed tomography before conventional coronary angiography. The incidence of MB was identified in 135 patients (35.4%) with 93.9% identified in the left anterior descending artery. MB were divided as partially encased versus fully encased. There was no difference in ischemia identified between partially encased MB and fully encased MB (37 [40%] vs 25 [35%], p = 0.54]. Ischemia was identified at similar rates in partially versus fully encased MB by single-photon emission computed tomography at (8 [9%] vs 8 [11%], p = 0.57] and CTP (34 [37%] vs 21 [30%], p = 0.33]. There was no difference in the primary outcome of 5-year outcome of combined incidence of myocardial infarction or death. The restricted mean survival time in patients with CTA with <50% stenosis with or without a MB was 4.906 years (95% confidence interval 4.759 to 5.000) and 4.891 years (95% confidence interval 4.718 to 5.000), respectively (p = 0.824). Cardiac computed tomography perfusion imaging can assess both anatomic and functional significance of myocardial bridging with diagnostic accuracy similar to current standard imaging. Furthermore, 5-year cardiovascular events were not different with the presence of MB in both obstructive and non-obstructive CAD.

Periodontal Disease Associated With Interstitial Myocardial Fibrosis: The Multiethnic Study of Atherosclerosis.

Background Periodontitis is a chronic inflammatory disease common among adults. It has been suggested that periodontal disease (PD) may be a contributing risk factor for cardiovascular disease; however, pathways underlying such a relationship require further investigation. Methods and Results A total of 665 men (mean age 68±9 years) and 611 women (mean age 67±9 years) enrolled in the MESA (Multiethnic Study of Atherosclerosis) underwent PD assessment using a 2-item questionnaire at baseline (2000-2002) and had cardiovascular magnetic resonance 10 years later. PD was defined when participants reported either a history of periodontitis or gum disease or lost teeth caused by periodontitis or gum disease. Multivariable linear regression models were constructed to assess the associations of baseline self-reported PD with cardiovascular magnetic resonance-obtained measures of interstitial myocardial fibrosis (IMF), including extracellular volume and native T1 time. Men with a self-reported history of PD had greater extracellular volume percent (ß=0.6%±0.2, P=0.01). This association was independent of age, left ventricular mass, traditional cardiovascular risk factors, and history of myocardial infarction. In a subsequent model, substituting myocardial infarction for coronary artery calcium score, the association of PD with IMF remained significant (ß=0.6%±0.3, P=0.03). In women, a self-reported history of PD was not linked to higher IMF. Importantly, a self-reported history of PD was not found to be associated with myocardial scar independent of sex (odds ratio, 1.01 [95% CI, 0.62-1.65]; P=0.9). Conclusions In a community-based setting, men but not women with a self-reported PD history at baseline were found to be associated with increased measures of IMF. These findings support a plausible link between PD, a proinflammatory condition, and subclinical IMF.

Quality assessment of cardiac magnetic resonance myocardial scar imaging prior to ventricular arrhythmia ablation.

High-resolution scar characterization using late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) is useful for guiding ventricular arrhythmia (VA) treatment. However, imaging study quality may be degraded by breath-holding difficulties, arrhythmias, and implantable cardioverter-defibrillators (ICDs). We evaluated the effect of image quality on left ventricle (LV) base to apex scar interpretation in pre-VA ablation LGE-CMR. 43 consecutive patients referred for VA ablation underwent gradient-recalled-echo LGE-CMR. In ICD patients (n = 24), wide-bandwidth inversion-recovery suppressed ICD artifacts. In non-ICD patients, single-shot steady-state free-precession LGE-CMR could also be performed to reduce respiratory motion/arrhythmia artifacts. Study quality was assessed for adequate/limited scar interpretation due to cardiac/respiratory motion artifacts, ICD-related artifacts, and image contrast. 28% of non-ICD patients had studies where image quality limited scar interpretation in at least one image compared to 71% of ICD patient studies (p = 0.012). A median of five image slices had limited quality per ICD patient study, compared to 0 images per non-ICD patient study. Poorer quality in ICD patients was largely due to motion-related artifacts (54% ICD vs 6% non-ICD studies, p = 0.001) as well as ICD-related image artifacts (25% of studies). In VA ablation patients with ICDs, conventional CMR protocols frequently have image slices with limited scar interpretation, which can limit whole-heart scar assessment. Motion artifacts contribute to suboptimal image quality, particularly in ICD patients. Improved methods for motion and ICD artifact suppression may better delineate high-resolution LGE scar features of interest for guiding VA ablation.

Prognostic value of a left atrioventricular coupling index in pre- and post-menopausal women from the Multi-Ethnic Study of Atherosclerosis.

Background: Sex hormones associated with both the left atrial (LA) and left ventricular (LV) structures in women, but the association of menopause status with left atrioventricular coupling is not established. Aim: To assess the prognostic value of a left atrioventricular coupling index (LACI) in peri-menopausal women without a history of cardiovascular disease (CVD). Materials and methods: In all women participating in MESA study with baseline cardiovascular MRI, the LACI was measured as the ratio of the LA end-diastolic volume to the LV end-diastolic volume. Cox models were used to assess the association between the LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), coronary heart disease (CHD) death, and hard CVD. Results: Among the 2,087 women participants (61 ± 10 years), 485 cardiovascular events occurred (mean follow-up: 13.2 ± 3.3 years). A higher LACI was independently associated with AF (HR 1.70; 95%CI [1.51-1.90]), HF (HR 1.62; [1.33-1.97]), CHD death (HR 1.36; [1.10-1.68]), and hard CVD (HR 1.30; [1.13-1.51], all p < 0.001). Adjusted models with the LACI showed significant improvement in model discrimination and reclassification when compared to traditional models to predict: incident AF (C-statistic: 0.82 vs. 0.79; NRI = 0.325; IDI = 0.036), HF (C-statistic: 0.84 vs. 0.81; NRI = 0.571; IDI = 0.023), CHD death (C-statistic: 0.87 vs. 0.85; NRI = 0.506; IDI = 0.012), hard CVD (C-statistic: 0.78 vs. 0.76; NRI = 0.229; IDI = 0.012). The prognostic value of the LACI had a better discrimination and reclassification than individual LA or LV parameters. Conclusion: In a multi-ethnic population of pre- and post-menopausal women, the LACI is an independent predictor of HF, AF, CHD death, and hard CVD. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT00005487].

Change in Left Atrioventricular Coupling Index to Predict Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background Left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic values as predictors of atrial fibrillation (AF). Purpose To investigate the prognostic value of a left atrioventricular coupling index (LACI) and average annualized change in LACI (hereafter, ΔLACI) measured by cardiac MRI to predict incident AF in a population-based sample from the Multi-Ethnic Study of Atherosclerosis (MESA). Materials and Methods In a secondary analysis of the prospective MESA, 1911 study participants without clinically recognized AF and cardiovascular disease at baseline had LACI assessed with cardiac MRI at baseline (examination 1, 2000-2002) and 10 years later (examination 5, 2010-2012). LACI was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average ΔLACI with incident AF. Results Among the 1911 participants (mean age, 59 years ± 9 [standard deviation]; 907 men), 87 incident AF events occurred over 3.9 years ± 0.9 after the second imaging (examination 5). After adjustment for traditional risk factors, greater LACI and ΔLACI were independently associated with AF (hazard ratio, 1.69 [95% CI: 1.46, 1.96] and 1.71 [95% CI: 1.50, 1.94], respectively; both P < .001). Adjusted models for LACI and ΔLACI showed improvement in model discrimination compared with currently used AF risk score (Cohort for Heart and Aging Research in Genomic Epidemiology-Atrial Fibrillation, or CHARGE-AF, score) model (area under receiver operating characteristic curve [AUC], 0.78 vs 0.74; and AUC, 0.80 vs 0.74, respectively; both P < .001); and to the final model including individual LA or LV parameters for predicting AF incidence (AUC, 0.78 vs 0.76; and AUC, 0.80 vs 0.78, respectively; both P < .001). Conclusion Atrioventricular coupling (left atrioventricular coupling index [LACI]) and coupling change (annual change in LACI) were strong predictors for atrial fibrillation (AF) in a multiethnic population. Both had incremental prognostic value for predicting AF over traditional risk factors, and superior discrimination compared with the Cohort for Heart and Aging Research in Genomic Epidemiology-Atrial Fibrillation, or CHARGE-AF, score and to individual left atrial or left ventricular parameters. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leiner in this issue.

Left Atrioventricular Coupling Index to Predict Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis.

Background: Although left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic value as predictors of heart failure (HF), the close physiological relationship between the LA and LV suggest that the assessment of LA/LV coupling could better reflect left atrioventricular dysfunction and be a better predictor of HF. Aim: We investigated the prognostic value of a left atrioventricular coupling index (LACI), measured by cardiovascular magnetic resonance (CMR), as well as change in LACI to predict incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA). Materials and Methods: In the MESA, 2,250 study participants, free of clinically recognized HF and cardiovascular disease (CVD) at baseline, had LACI assessed by CMR imaging at baseline (Exam 1, 2000-2002), and 10 years later (Exam 5, 2010-2012). Left atrioventricular coupling index was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident HF after adjustment for traditional MESA-HF risk factors. The incremental risk prediction was calculated using C-statistic, categorical net reclassification index (NRI) and integrative discrimination index (IDI). Results: Among the 2,250 participants (mean age 59.3 ± 9.3 years and 47.6% male participants), 50 incident HF events occurred over 6.8 ± 1.3 years after the second CMR exam. After adjustment, greater LACI and ΔLACI were independently associated with HF (adjusted HR 1.44, 95% CI [1.25-1.66] and adjusted HR 1.55, 95% CI [1.30-1.85], respectively; both p < 0.0001). Adjusted models for LACI showed significant improvement in model discrimination and reclassification compared to currently used HF risk score model for predicting HF incidence (C-statistic: 0.81 vs. 0.77; NRI = 0.411; IDI = 0.043). After adjustment, ΔLACI showed also significant improvement in model discrimination compared to the multivariable model with traditional MESA-HF risk factors for predicting incident HF (C-statistic: 0.82 vs. 0.77; NRI = 0.491; IDI = 0.058). Conclusions: In a multi-ethnic population, atrioventricular coupling (LACI), and coupling change (ΔLACI) are independently associated with incident HF. Both have incremental prognostic value for predicting HF events over traditional HF risk factors.

Left Atrioventricular Coupling Index as a Prognostic Marker of Cardiovascular Events: The MESA Study.

[Figure: see text].

Association between interatrial block, left atrial fibrosis, and mechanical dyssynchrony: Electrocardiography-magnetic resonance imaging correlation.

INTRODUCTION: Advanced interatrial block (IAB) on a 12-lead electrocardiogram (ECG) is a predictor of stroke, incident atrial fibrillation (AF), and AF recurrence after catheter ablation. The objective of this study was to determine which features of IAB structural remodeling is associated with left atrium (LA) magnetic resonance imaging structure and function. METHODS/RESULTS: We included 152 consecutive patients (23% nonparoxysmal AF) who underwent preprocedural ECG and cardiac magnetic resonance (CMR) in sinus rhythm before catheter ablation of AF. IAB was defined as P-wave duration ≥120 ms, and was considered partial if P-wave was positive and advanced if P-wave had a biphasic morphology in inferior leads. From cine CMR and late gadolinium enhancement, we derived LA maximum and minimum volume indices, strain, LA fibrosis, and LA dyssynchrony. A total of 77 patients (50.7% paroxysmal) had normal P-wave, 52 (34.2%) partial IAB, and 23 (15.1%) advanced IAB. Patients with advanced IAB had significantly higher LA minimum volume index (25.7 vs 19.9 mL/m2 , P = .010), more LA fibrosis (21.9% vs 13.1%, P = .020), and lower LA maximum strain rate (0.99 vs 1.18, P = .007) than those without. Advanced IAB was independently associated with LA (minimum [P = .032] and fibrosis [P = .009]). P-wave duration was also independently associated with LA fibrosis (ß = .33; P = .049) and LA mechanical dyssynchrony (ß = 2.01; P = .007). CONCLUSION: Advanced IAB is associated with larger LA volumes, lower emptying fraction, and more fibrosis. Longer P-wave duration is also associated with more LA fibrosis and higher LA mechanical dyssynchrony.

Understanding Atrial Cardiopathy: an Under-Recognized Contributor to Cardioembolic Stroke.

PURPOSE OF REVIEW: Ischemic stroke is the fifth leading cause of death in the world with cardioembolic stroke (CES) causing a disproportional amount of the morbidity and mortality associated with stroke. Atrial fibrillation (AF) is the leading cause of CES, and as the population ages, the incidence of CES is anticipated to rise. The importance of proper diagnosis and treatment of patients with embolic-appearing stroke is significant due to the burden of disease and the severity of the illness. RECENT FINDINGS: The past decade has seen an explosion of treatment options for patients with CES related to AF as well as better mechanisms by which to monitor and diagnose patients with AF. While optimal secondary prevention of stroke with anticoagulation in the setting of AF is known, what remains to be defined is the appropriate treatment of other types of strokes that appear embolic, but no source of the embolism is discovered. In this article, we will review what is known about the diagnosis and treatment of CES, discuss the emergence of novel therapeutics and emphasize what must be investigated in the future to move the field forward, such as the emerging concept of atrial cardiopathy.

Echocardiographic Pulmonary Artery Systolic Pressure in the Coronary Artery Risk Development in Young Adults (CARDIA) Study: Associations With Race and Metabolic Dysregulation.

BACKGROUND: The determinants of pulmonary artery systolic pressure (PASP) are not fully understood. It is unknown whether racial differences in PASP exist or if other population characteristics are associated with pulmonary pressure in humans. We examined echocardiographically estimated PASP in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a middle-aged, biracial community-based cohort. METHODS AND RESULTS: At the CARDIA year-25 examination, 3469 participants underwent echocardiography, including measurement of tricuspid regurgitant jet velocity to estimate PASP. Clinical features, laboratory values, pulmonary function tests, and measurement of adipose depot volume were analyzed for association with PASP. PASP was estimated in 1311 individuals (61% female, 51% white). Older age, higher blood pressure, and higher body mass index were associated with higher PASP. Black race was associated with higher PASP after adjustment for demographics and left and right ventricular function (ß 0.94, 95% CI 0.24-1.64; P=0.009), but this association was no longer significant after further adjustment for lung volume (ß 0.42, 95% CI -0.68 to 0.96; P=0.74). Insulin resistance, inflammation (C-reactive protein and interleukin-6), and visceral adipose volume were independently associated with higher PASP after adjustment for relevant covariates. PASP rose with worsening diastolic function (ratio of early transmitral Doppler velocity to average mitral annular tissue Doppler velocity [E/e'] and left atrial volume index). CONCLUSIONS: In a large biracial cohort of middle-aged adults, we identified associations among black race, insulin resistance, and diastolic dysfunction with higher echocardiographically estimated PASP. Further studies are needed to examine racial differences in PASP and whether insulin resistance directly contributes to pulmonary vascular disease in humans.