Assessing breast arterial calcification in mammograms and its implications for atherosclerotic cardiovascular disease risk.

PURPOSE: Breast arterial calcifications (BAC) are incidentally observed on mammograms, yet their implications remain unclear. We investigated lifestyle, reproductive, and cardiovascular determinants of BAC in women undergoing mammography screening. Further, we investigated the relationship between BAC, coronary arterial calcifications (CAC) and estimated 10-year atherosclerotic cardiovascular (ASCVD) risk. METHODS: In this cross-sectional study, we obtained reproductive history and CVD risk factors from 215 women aged 18 or older who underwent mammography and cardiac computed tomographic angiography (CCTA) within a 2-year period between 2007 and 2017 at hospital. BAC was categorized as binary (present/absent) and semi-quantitatively (mild, moderate, severe). CAC was determined using the Agatston method and recorded as binary (present/absent). Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated, accounting for age as a confounding factor. ASCVD risk over a 10-year period was calculated using the Pooled Cohort Risk Equations. RESULTS: Older age, systolic and diastolic blood pressures, higher parity, and younger age at first birth (≤28 years) were significantly associated with greater odds of BAC. Women with both BAC and CAC had the highest estimated 10-year risk of ASCVD (13.30 %). Those with only BAC (8.80 %), only CAC (5.80 %), and no BAC or CAC (4.40 %) had lower estimated 10-year risks of ASCVD. No association was detected between presence of BAC and CAC. CONCLUSIONS: These findings support the hypothesis that BAC on a screening mammogram may help to identify women at potentially increased risk of future cardiovascular disease without additional cost and radiation exposure.

A Combined Measure of the Triglyceride Glucose Index and Trimethylamine N-Oxide in Risk Stratification of ST-Segment Elevation Myocardial Infarction Patients with High-Risk Plaque Features Defined by Optical Coherence Tomography: A Substudy of the OCTAMI Registry Study.

Background and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown. Methods: We studied 274 consecutive aged ≥18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019. Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723-0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p=0.033). A similar tendency was found in the cohort with hyperlipidemia (p=0.016) and diabetes mellitus (p=0.036). Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics. Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.

Association of different milk fat content with coronary artery disease and myocardial infarction risk: A Mendelian randomization study.

BACKGROUND: Numerous observational studies have investigated on the correlation of whole, semi-skimmed, and skimmed milk with coronary artery disease (CAD) and myocardial infarction (MI) risk; However, no consensus has been reached and evidence on any causal links between these exposures and outcomes remains unclear. This study aimed to conduct univariate and multivariate Mendelian randomization (MR) analyses, using publicly released genome-wide association study summary statistics (GWAS) from the IEU GWAS database, to ascertain the causal association of milk with various fat content with CAD and MI risk. METHODS: For the exposure data, 29, 15, and 30 single-nucleotide polymorphisms for whole milk, semi-skimmed milk, and skimmed milk, respectively, obtained from 360,806 Europeans, were used as instrumental variables. CAD and MI comprised 141,217 and 395,795 samples, respectively. We used inverse variance weighted (IVW), weighted median, MR-Egger regression, and MR Pleiotropy Residual Sum and Outlier analyses to determine whether pleiotropy and heterogeneity could skew the MR results. Sensitivity tests were conducted to verify the robustness of the results. RESULTS: After adjusting for false discovery rates (FDR), we discovered proof that skimmed milk intake is a genetically predicted risk factor for CAD (odds ratio [OR] = 5.302; 95% confidence interval [CI] 2.261-12.432; P < 0.001; FDR-corrected P < 0.001) and MI (OR = 2.287; 95% CI 1.218-4.300; P = 0.010; FDR-corrected P = 0.009). Most sensitivity assessments yielded valid results. Multivariable MR for CAD and MI produced results consistent with those obtained using the IVW method. There was no causal relationship between whole or semi-skimmed milk, and CAD or MI. CONCLUSION: Our findings indicate that the consumption of skimmed milk may increase the risk of CAD and MI. This evidence may help inform dietary recommendations for preventing cardiovascular disease. Further studies are required to elucidate the underlying mechanisms.

Metabolic Obesity Phenotypes and Incident Cardiovascular Outcomes in Middle-Aged and Older Korean Adults: A Longitudinal 10-Year Analysis of the Korean Genome and Epidemiology Study.

Background: This study investigated the association of four metabolic obesity phenotypes with incident coronary artery disease and stroke in a large-scale, community population-based, prospective Korean cohort observed for over 10 years. Methods: The study participants included 7374 adults aged 40-69 years, drawn from the Korean Genome and Epidemiology Study. Participants with different metabolic obesity phenotypes were categorized according to body weight and metabolic health status into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUHNO), and metabolically unhealthy obese (MUHO). Combined cardiovascular events were defined as coronary artery disease and stroke. We used multivariate Cox proportional hazards regression models to prospectively assess hazard ratios (HRs) with 95% confidence intervals (CIs) for incident coronary artery disease or stroke over 10 years after the baseline survey. Results: During the follow-up period, newly developed coronary artery disease, stroke, and combined cardiovascular events were diagnosed in 151 (2.0%), 137 (1.9%), and 283 (3.8%) participants, respectively. After adjusting for confounding variables, the HRs (95% CIs) for incident combined cardiovascular events were 1.81 (1.34-2.46) in the MUHO group, 1.29 (0.92-1.81) in the MUHNO group, and 1.21 (0.81-1.79) in the MHO group compared with those in the MHNO group. Conclusions: This study revealed distinct risks associated with four metabolic obesity phenotypes concerning incident coronary artery disease and stroke. After adjusting for potential confounding variables, the results indicated that MUHO, but not MUHNO or MHO, showed a higher risk of developing coronary artery disease and stroke than MHNO.

Iron Status and Risk of Heart Disease, Stroke, and Diabetes: A Mendelian Randomization Study in European Adults.

BACKGROUND: The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases. METHODS AND RESULTS: Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank. Iron biomarkers included transferrin saturation, serum iron, ferritin, and total iron binding capacity. MR analyses assessed associations with CAD (CARDIOGRAMplusC4D [Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus The Coronary Artery Disease Genetics], n=181 522 cases), HF (HERMES [Heart Failure Molecular Epidemiology for Therapeutic Targets), n=115 150 cases), IS (GIGASTROKE, n=62 100 cases), and T2D (DIAMANTE [Diabetes Meta-Analysis of Trans-Ethnic Association Studies], n=80 154 cases) genome-wide consortia. Observational analyses demonstrated J-shaped associations of hemoglobin with CAD, HF, IS, and T2D. In contrast, MR analyses demonstrated linear positive associations of higher genetically predicted hemoglobin levels with 8% higher risk per 1 SD higher hemoglobin for CAD, 10% to 13% for diabetes, but not with IS or HF in UK Biobank. Bidirectional MR analyses confirmed the causal relevance of iron biomarkers for hemoglobin. Further MR analyses in global consortia demonstrated modest protective effects of iron biomarkers for CAD (7%-14% lower risk for 1 SD higher levels of iron biomarkers), adverse effects for T2D, but no associations with IS or HF. CONCLUSIONS: Higher levels of iron biomarkers were protective for CAD, had adverse effects on T2D, but had no effects on IS or HF. Randomized trials are now required to assess effects of iron supplements on risk of CAD in high-risk older people.

Influence of COVID-19 pandemic in India on coronary artery disease clinical presentation, angiography, interventions and in-hospital outcomes: a single centre prospective registry-based observational study.

OBJECTIVE: The study examined the influence of the COVID-19 pandemic in India on variation in clinical features, management and in-hospital outcomes in patients undergoing percutaneous coronary intervention (PCI). DESIGN: Prospective registry-based observational study. SETTING: A tertiary care hospital in India participant in the American College of Cardiology CathPCI Registry. PARTICIPANTS: 7089 successive patients who underwent PCI from April 2018 to March 2023 were enrolled (men 5627, women 1462). Details of risk factors, clinical presentation, coronary angiography, coronary interventions, clinical management and in-hospital outcomes were recorded. Annual data were classified into specific COVID-19 periods according to Government of India guidelines as pre-COVID-19 (April 2018 to March 2019, n=1563; April 2019 to March 2020, n=1594), COVID-19 (April 2020 to March 2020, n=1206; April 2021 to March 2022, n=1223) and post-COVID-19 (April 2022 to March 2023, n=1503). RESULTS: Compared with the patients in pre-COVID-19 and post-COVID-19 periods, during the first COVID-19 year, patients had more hypertension, non-ST elevation myocardial infarction (NSTEMI), lower left ventricular ejection fraction (LVEF) and multivessel coronary artery disease (CAD). In the second COVID-19 year, patients had more STEMI, lower LVEF, multivessel CAD, primary PCI, multiple stents and more vasopressor and mechanical support. There were 99 (1.4%) in-hospital deaths which in the successive years were 1.2%, 1.4%, 0.8%, 2.4% and 1.3%, respectively (p=0.019). Compared with the baseline year, deaths were slightly lower in the first COVID-19-year (age-sex adjusted OR 0.68, 95% CI 0.31 to 1.47) but significantly more in the second COVID-19-year (OR 1.97, 95% CI 1.10 to 3.54). This variation attenuated following adjustment for clinical presentation, extent of CAD, in-hospital treatment and duration of hospitalisation. CONCLUSIONS: In-hospital mortality among patients with CAD undergoing PCI was significantly higher in the second year of the COVID-19 pandemic in India and could be one of the reasons for excess deaths in the country. These patients had more severe CAD, lower LVEF, and more vasopressor and mechanical support and duration of hospitalisation.

Association between obstructive coronary disease and diabetic retinopathy: Cross-sectional study of coronary angiotomography and multimodal retinal imaging.

AIMS: To investigate the association between diabetic retinopathy (DR) and coronary artery disease (CAD) using coronary angiotomography (CCTA) and multimodal retinal imaging (MMRI) with ultra-widefield retinography and optical coherence tomography angiography and structural domain. METHODS: Single-center, cross-sectional, single-blind. Patients with diabetes who had undergone CCTA underwent MMRI. Uni and multivariate analysis were used to assess the association between CAD and DR and to identify variables independently associated with DR. RESULTS: We included 171 patients, 87 CAD and 84 non-CAD. Most CAD patients were males (74 % vs 38 %, P < 0.01), insulin users (52 % vs 38 %, p < 0.01) and revascularized (64 %). They had a higher prevalence of DR (48 % vs 22 %, p = 0.01), microaneurysms (25 % vs 13 %, p = 0.04), intraretinal cysts (22 % vs 8 %, p = 0.01) and areas of reduced capillary density (46 % vs 20 %, p < 0.01). CAD patients also had lower mean vascular density (MVD) (15.7 % vs 16.5,%, p = 0.049) and foveal avascular zone (FAZ) circularity (0.64 ± 0.1 vs 0.69 ± 0.1, p = 0.04). There were significant and negative correlations between Duke coronary score and MVD (r = -0.189; p = 0.03) and FAZ circularity (r = -0,206; p = 0.02). CAD, DM duration and insulin use independently associated with DR. CONCLUSIONS: CAD patients had higher prevalence of DR and lower MVD. CAD, DM duration and insulin use were independently associated with DR.

Omega-3 fatty acids and their influence on hypertension and coronary atherosclerosis: Insights from a Mendelian randomization approach.

It has been suggested that Omega-3 fatty acids may improve endothelial thickness and thereby reduce the onset of cardiovascular diseases such as coronary atherosclerosis and hypertension. However, published observational epidemiological studies on the relationship between cardiovascular disease (CVD) and Omega-3 fatty acids remain inconclusive. Here, we performed a two-sample Mendelian randomisation analysis using publicly available GWAS pooled statistics to study a GWAS dataset of 16 380 466 SNPs in 23 363 cases and 195 429 controls (also of European ancestry) to determine genetic susceptibility to hypertension. We performed random-effects Inverse Variance Weighted (IVW) Mendelian Randomization (MR) analyses supplemented by a series of sensitivity assessments to measure the robustness of the findings and to detect any violations of the MR assumptions. During the course of the study, we used IVW, MR-Egger, and weighted median regression to infer that Omega-3 intake has a potentially adverse effect against atherosclerosis, although the trend was not significant (OR = 1.1198; 95%; CI: 0.9641-1.3006, p = .130). Meanwhile, our analyses showed a statistically significant negative association between Omega-3 fatty acid levels and risk of hypertension (OR = 0.9006; 95% CI: 0.8179-0.9917, p = .033). In addition, we explored the causal relationship between atherosclerosis and hypertension and found a significant correlation (OR = 1.3036; 95% CI: 1.0672-1.5923, p = .009). In conclusion, our extensive data investigated by MR suggest that elevated levels of Omega-3 fatty acids may be associated with an decreased risk of hypertension. Although there is no direct link between hypertension and atherosclerosis, the possibility of a subtle association cannot be categorically excluded.

Evaluating the association between opium abuse, blood lead levels, and the complexity of coronary artery disease.

Opium abuse and exposure to heavy metals elevate the risk of coronary artery disease (CAD). Therefore, we aimed to determine the association between opium abuse and blood lead levels (BLLs) and the CAD complexity. We evaluated patients with acute coronary symptoms who underwent coronary angiography, and those with >50% stenosis in at least one of the coronary arteries were included. Furthermore, Synergy between PCI with Taxus and Cardiac Surgery I (SYNTAX I) score and BLLs were measured. Based on the opium abuse, 95 patients were subdivided into opium (45) and control (50) groups. Differences in demographics and CAD risk factors were insignificant between the two groups. The median BLLs were remarkably higher in the opium group than in controls (36 (35.7) and 20.5 µg/dL (11.45), respectively, p = 0.003). We also revealed no significant differences in SYNTAX score between the two groups (15.0 (9.0) and 17.5 (14.0), respectively, p = 0.28). Additionally, we found no significant correlation between BLLs and the SYNTAX scores (p = 0.277 and r = -0.113). Opium abuse was associated with high BLLs. Neither opium abuse nor high BLLs were correlated with the complexity of CAD. Further studies are warranted to establish better the relationship between opium abuse, BLLs, and CAD.

Spectrum of Ischemic Heart Disease Throughout a Woman's Life Cycle.

Ischemic heart disease (IHD) is the leading cause of morbidity and mortality in both genders; however, young women fare the worst, likely reflecting the more complex spectrum of IHD in women when compared to men. Substantial sex-based differences exist in the underlying risk factors, risk enhancers, presentation, diagnosis, and pathophysiology of IHD that are mainly attributed to the influence of female sex hormones. This article reviews the spectrum of IHD including obstructive epicardial coronary artery disease (CAD), myocardial infarction with no obstructive coronary artery disease, ischemia with no obstructive coronary artery disease, spontaneous coronary artery dissection, coronary microvascular dysfunction, vasospastic angina, and coronary thrombosis/embolism that occur in women throughout various stages of their life cycle. We aim to update clinicians on the diagnosis and management of these various types of IHD and highlight where further randomized controlled studies are needed to determine optimal treatment and inform guideline-directed medical therapy.

The Intersection of Atrial Fibrillation and Coronary Artery Disease in Middle Eastern Patients. Analysis from the Jordan Atrial Fibrillation Study.

Background: There is a scarcity of clinical studies which evaluate the association of atrial fibrillation (AF) and coronary artery disease (CAD) in the Middle East. The aim of this study was to evaluate the impact of CAD on baseline clinical profiles and one-year outcomes in a Middle Eastern cohort with AF. Methods: Consecutive AF patients evaluated in 29 hospitals and cardiology clinics were enrolled in the Jordan AF Study (May 2019-December 2020). Clinical and echocardiographic features, use of medications and one-year outcomes in patients with AF/CAD were compared to AF/no CAD patients. Results: Of 2020 AF patients enrolled, 216 (10.7%) had CAD. Patients with AF/CAD were more likely to be men and had significantly higher prevalence of hypertension, diabetes, dyslipidemia, heart failure and chronic kidney disease compared to the AF/no CAD patients. They also had lower mean left ventricular ejection fraction and larger left atrial size. Mean CHA2DS2 VASc and HAS-BLED scores were higher in AF/CAD patients than those with AF/no CAD (4.3 ± 1.7 vs. 3.6 ± 1.8, p < 0.0001) and (2.0 ± 1.1 vs. 1.6 ± 1.1, p < 0.0001), respectively. Oral anticoagulant agents were used in similar rates in the two groups (83.8% vs. 82.9%, p = 0.81), but more patients with AF/CAD were prescribed additional antiplatelet agents compared to patients with AF/no CAD (73.7% vs. 41.5%, p < 0.0001). At one year, AF/CAD patients, compared to AF/no CAD patients had significantly higher hospitalization rate (39.4% vs. 29.2%, p = 0.003), more acute coronary syndrome and coronary revascularization (6.9% vs. 2.4%, p = 0.004), and higher all-cause mortality (18.5% vs. 10.9%, p = 0.002). Conclusions: In this cohort of Middle Eastern patients with AF, one in 10 patients had CAD. The coexistence of AF and CAD was associated with a worse baseline clinical profile and one-year outcomes. Clinical study registration: the study is registered on clinicaltrials.gov (unique identifier number NCT03917992).

Incidence, Predictors, and Impact of Hospital Readmission After Revascularization for Left Main Coronary Disease.

BACKGROUND: The frequency of and relationship between hospital readmissions and outcomes after revascularization for left main coronary artery disease (LMCAD) are unknown. OBJECTIVES: The purpose of this study was to study the incidence, predictors, and clinical impact of readmissions following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for LMCAD. METHODS: In the EXCEL (XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, 1,905 patients with LMCAD were randomized to PCI vs CABG. The cumulative incidence of readmissions was analyzed with multivariable Anderson-Gill and joint frailty models to account for recurrent events and the competing risk of death. The impact of readmission on subsequent mortality within 5-year follow-up was determined in a time-adjusted Cox proportional hazards model. RESULTS: Within 5 years, 1,868 readmissions occurred in 851 of 1,882 (45.2%) hospital survivors (2.2 ± 1.9 per patient with readmission[s], range 1-16), approximately one-half for cardiovascular causes and one-half for noncardiovascular causes (927 [49.6%] and 941 [50.4%], respectively). One or more readmissions occurred in 463 of 942 (48.6%) PCI patients vs 388 of 940 (41.8%) CABG patients (P = 0.003). After multivariable adjustment, PCI remained an independent predictor of readmission (adjusted HR: 1.22; 95% CI: 1.10-1.35; P < 0.0001), along with female sex, comorbidities, and the extent of CAD. Readmission was independently associated with subsequent all-cause death, with interaction testing indicating a higher risk after PCI than CABG (adjusted HR: 5.72; 95% CI: 3.42-9.55 vs adjusted HR: 2.72; 95% CI: 1.64-4.88, respectively; Pint = 0.03). CONCLUSIONS: In the EXCEL trial, readmissions during 5-year follow-up after revascularization for LMCAD were common and more frequent after PCI than CABG. Readmissions were associated with an increased risk of all-cause death, more so after PCI than with CABG.

[Multidistrict atherosclerotic disease: epidemiological and clinical framework]. / Malattia aterosclerotica polidistrettuale: inquadramento epidemiologico e clinico.

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.

A Step towards understanding coronary artery disease: a complication in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a relatively rare disease with increasing incidence trends. Cardiovascular disease is a significant complication in IPF patients due to the role of common proatherogenic immune mediators. The prevalence of coronary artery disease (CAD) in IPF and the association between these distinct pathologies with overlapping pathophysiology remain less studied. RESEARCH QUESTION: We hypothesised that IPF is an independent risk factor for CAD. METHODS: We conducted a retrospective case-control study using the national inpatient sample (2017-2019). We included adult hospitalisations with IPF after excluding other interstitial lung diseases and other endpoints of CAD, acute coronary syndrome and old myocardial infarction. We examined their baseline characteristics, such as demographic data, hospital characteristics and socioeconomic status. The prevalence of cardiac risk factors and CAD was also compared between hospitalisations with and without IPF. Univariate and multivariate regression analysis was further performed to study the odds of CAD with IPF. The cases of IPF in the study population were propensity-matched, after which generalised linear modelling analysis was performed to validate the findings. RESULTS: A total of 116 010 admissions were hospitalised in 2017-2019 with IPF, of which 55.6% were men with a mean age of 73 years. Adult hospitalisations with IPF were found to have a higher prevalence of diabetes mellitus (29.3% vs 24.0%; p<0.001), hypertension (35.6% vs 33.8%; p<0.001), hyperlipidaemia (47.7% vs 30.2%; p<0.0001) and tobacco abuse (41.7% vs 20.9%; p<0.001), while they had a lower prevalence of obesity (11.7% vs 15.3%; p<0.0001) compared with hospitalisations without IPF. Multivariate logistic regression analysis revealed 28% higher odds of developing CAD in IPF hospitalisations (OR -1.28; CI 1.22 to 1.33; p<0.001). Postpropensity matching, generalised linear modelling analysis revealed even higher odds of CAD with IPF (OR -1.77; CI 1.54 to 2.02; p<0.001) CONCLUSIONS: Our study found a higher prevalence of CAD in IPF hospitalisations and significantly higher odds of CAD among IPF cases. IPF remains a terminal lung disease that portends a poor prognosis, but addressing the cardiovascular risk factors in these patients can help reduce the case fatality rate due to the latter and potentially add to quality-adjusted life years.

Epidemiological and biological associations between cardiovascular disease and kidney stone formation: A systematic review and meta-analysis.

AIMS: Previous studies find kidney stone formers (KSF) are at greater risk of developing cardiovascular disease (CVD). The underlying mechanisms are poorly understood, and many clinicians are unaware of this connection. We will: DATA SYNTHESIS: Our systematic review is registered with PROSPERO (ID CRD42021251477). We searched epidemiological and biological data. The epidemiological search generated 669 papers, narrowed down to 15. There were 4,259,869 participants (230,720 KSFs). KSF was associated with 25% higher risk of coronary artery disease (CAD) (95% confidence interval (CI): 15, 35%), 17% higher risk of stroke/transient ischemic attacks (TIA) (CI:10, 25%) and 39% higher risk of arterial disease (AD) (CI: 17 65%). Significant heterogeneity was found. Female-identifying KSFs had a higher risk of stroke (ratio = 1.10) and CAD (1.20). The biological search generated 125 papers, narrowed down to 14. Potential underlying mechanisms were extracted and discussed, including intimal/medial vascular calcification, oxidative stress via osteopontin (OPN), cholesterol-induced pathology, and endothelial dysfunction. CONCLUSIONS: There is a significant association between KSF and CVD, supporting the consideration of KSF as a systemic, calcium-mediated disease. Clinicians will benefit from being aware of this connection.

Coronary microvascular dysfunction: prevalence and aetiology in patients with suspected myocardial ischaemia.

AIM: To evaluate the prevalence, aetiology, and corresponding morbidity of coronary microvascular dysfunction (CMD) in patients with suspected myocardial ischaemia. MATERIALS AND METHODS: The present study included 115 patients with suspected myocardial ischaemia who underwent stress perfusion cardiac magnetic resonance imaging. CMD was assessed visually based on the myocardial perfusion results. The CMR-derived myocardial perfusion reserve index (MPRI) and left ventricular (LV) strain parameters obtained using the post-processing software CVI42 were employed to evaluate LV myocardial perfusion and deformation. LV strain parameters included global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS), global systolic/diastolic longitudinal, circumferential, and radial strain rates (SLSR, SCSR, SRSR, DLSR, DCSR, and DRSR). RESULTS: Of the 115 patients, 12 patients were excluded and 103 patients were finally included in the study. CMD was observed in 79 % (81 patients, aged 53 ± 12 years) of patients. Regarding aetiology, 91 (88 %) patients had non-obstructive coronary artery disease (CAD), eight (8 %) had obstructive CAD, and four (4 %) had hypertrophic cardiomyopathy (HCM). The incidence of CMD was highest (100 %) in patients with HCM, followed by those with non-obstructive CAD (up to 79 %). There were no statistical differences between CMD and non-CMD groups in GCS, GRS, GLS, SRSR, SCSR, SLSR, DCSR, DRSR and DLSR. CONCLUSION: The incidence of CMD was higher in patients with signs and symptoms of ischaemia. CMD occurred with non-obstructive CAD, obstructive CAD, and HCM, with the highest prevalence of CMD in HCM.

Association of the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) Polymorphisms With Risk of Coronary Artery Disease in Iranian Patients.

BACKGROUND: Coronary artery disease (CAD) is a devastating illness and a leading cause of death worldwide, primarily caused by atherosclerosis resulting from a genetic-environmental interaction. This study aimed to investigate the relationship between the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) polymorphisms, lipid profile parameters, and CAD risk in a southeast Iranian population. METHODS: A total of 400 subjects (200 CAD patients with hyperlipidemia and 200 healthy controls) were enrolled in this case-control study. Five selected polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: For all single nucleotide polymorphisms (SNPs), the population under study was in the Hardy-Weinberg equilibrium. The T-risk allele frequency of rs2228570 was associated with an increased risk of CAD. The TT and CT genotypes of rs2228570 had also been associated with the risk of CAD. Additionally, the TT genotype was associated with higher serum low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) levels. The GG genotype of the rs3736234 was associated with higher body mass index (BMI) and triglyceride (TG) levels, and the AA genotype of the rs708272 was associated with higher HDL-c levels. Based on these findings, we propose that the VDR (rs2228570) polymorphism was associated with serum HDL-c and LDL-c levels and may serve as potential risk factors for CAD within the Iranian population. Moreover, rs3736234 and rs708272 influence the concentrations of TG and HDL-c, respectively. CONCLUSION: These findings provided insights into the complex interplay between genetic variations, cardiovascular risk, and lipid metabolism.

Prevalence and management of familial hypercholesterolaemia in patients with chest pain admitted to hospital: a retrospective observational study.

OBJECTIVES: Patients with familial hypercholesterolaemia (FH) are genetically burdened by a lifelong elevation of the low-density lipoprotein cholesterol (LDL-C) level, putting them at a very high risk of premature ischaemic heart disease (IHD). This study aims to assess the prevalence of FH among patients admitted for IHD and the preventive treatment status before admission. DESIGN: Observational, retrospective, register-based study. SETTING: Individuals discharged with a diagnosis of IHD were enrolled consecutively throughout 2012-2016 from the cardiac care units of two hospitals in Copenhagen. PARTICIPANTS: 4223 individuals were discharged during the period. Inclusion criteria for further investigation were the availability of one measurement of LDL-C at the time of admission. In total, 2797 individuals were included for further investigation. There were no exclusion criteria. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary objective has been to determine the prevalence of FH in the population. The secondary objective has been to determine the use of lipid-lowering therapy and to which extend the individuals reach their treatment goal. RESULTS: Among the 2797 consecutive patients evaluated, the prevalence of potential FH was 7.7% (1: 13) and 6.8% (1:15) had probably or definite FH. The prevalence of FH was age-dependent: Among the 680 patients (24.3%) with premature IHD (men <55 years/women <60 years), 136 patients (20.0%) had potential FH and 21 (3.1%) had probable/definite FH. None were diagnosed and almost none attained their treatment goal. CONCLUSIONS: There is still a massive lack of recognition of FH in patients admitted to a cardiac care unit with a diagnosis of IHD. Despite a measured high LDL-C, the diagnosis was not made for any patients not even in patients who were admitted at an early age or had a previous cardiovascular event.

Relationship between metabolically healthy obesity and coronary artery calcification.

There is a lack of consensus regarding universally accepted criteria for metabolic health (MH). A simple definition of MH was systematically derived in a recent prospective cohort study. The present cross-sectional study aimed to explore the applicability of these criteria in Korean population, using coronary calcification as an indicator of cardiovascular risk. In total, 1049 healthy participants, who underwent coronary artery calcification testing at university hospital health promotion centers between January and December 2022, were included. Applying the main components of the newly derived definition, MH was defined as follows: (1) systolic blood pressure < 130 mmHg and no use of blood pressure-lowering medication; (2) waist circumference < 90 cm for males and < 85 cm for females; and (3) absence of diabetes. Multivariate logistic regression was conducted to examine the odds ratio (OR) and 95 % confidence interval (CI) for coronary artery calcium score across different phenotypes. The prevalence of coronary artery calcification in this study was 41.1 %. Compared with metabolically healthy, normal weight subjects, those with the metabolically healthy obesity phenotype did not exhibit increased odds for coronary atherosclerosis. (OR 0.93 [95 % CI 0.48-1.79]) Conversely, metabolically unhealthy subjects had increased risk, regardless of their body mass index category (OR 3.10 [95 % CI 1.84-5.24] in metabolically unhealthy normal weight; OR 3.21 [95 % CI 1.92-5.37] in metabolically unhealthy overweight; OR 2.73 [95 % CI 1.72-4.33] in metabolically unhealthy obese phenotype). These findings suggest that the new definition for MH has the potential to effectively distinguish individuals at risk for cardiovascular disease from those who are not.

Non-alcoholic fatty liver disease biomarkers estimate cardiovascular risk based on coronary artery calcium score in type 2 diabetes: a cross-sectional study with two independent cohorts.

BACKGROUND: Studies have demonstrated that coronary artery calcification on one hand and non-alcoholic fatty liver disease (NAFLD) on the other hand are strongly associated with cardiovascular events. However, it remains unclear whether NAFLD biomarkers could help estimate cardiovascular risk in individuals with type 2 diabetes (T2D). The primary objective of the present study was to investigate whether the biomarkers of NAFLD included in the FibroMax® panels are associated with the degree of coronary artery calcification in patients with T2D. METHODS: A total of 157 and 460 patients with T2D were included from the DIACART and ACCoDiab cohorts, respectively. The coronary artery calcium score (CACS) was measured in both cohorts using computed tomography. FibroMax® panels (i.e., SteatoTest®, FibroTest®, NashTest®, and ActiTest®) were determined from blood samples as scores and stages in the DIACART cohort and as stages in the ACCoDiab cohort. RESULTS: CACS significantly increased with the FibroTest® stages in both the DIACART and ACCoDiab cohorts (p-value for trend = 0.0009 and 0.0001, respectively). In DIACART, the FibroTest® score was positively correlated with CACS in univariate analysis (r = 0.293, p = 0.0002) and remained associated with CACS independently of the traditional cardiovascular risk factors included in the SCORE2-Diabetes model [ß = 941 ± 425 (estimate ± standard error), p = 0.028]. In the ACCoDiab cohort, the FibroTest® F3-F4 stage was positively correlated with CACS in point-biserial analysis (rpbi = 0.104, p = 0.024) and remained associated with CACS after adjustment for the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (ß = 234 ± 97, p = 0.016). Finally, the prediction of CACS was improved by adding FibroTest® to the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (goodness-of-fit of prediction models multiplied by 4.1 and 6.7 in the DIACART and ACCoDiab cohorts, respectively). In contrast, no significant relationship was found between FibroMax® panels other than FibroTest® and CACS in either cohort. CONCLUSIONS: FibroTest® is independently and positively associated with the degree of coronary artery calcification in patients with T2D, suggesting that FibroTest® could be a relevant biomarker of coronary calcification and cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT02431234 and NCT03920683.