Association between atherosclerosis and height loss among older individuals.

Atherosclerosis and height loss are each reportedly associated with cardiovascular disease. However, no studies have found an association between atherosclerosis and height loss. A retrospective study of 2435 individuals aged 60-89 years who underwent annual health check-ups was conducted. Atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥ 1.1 mm. Height loss was defined as being in the highest quintile of height decrease per year, as in our previous studies. Among study participants, 555 were diagnosed as having atherosclerosis. Independent of known cardiovascular risk factors, atherosclerosis was positively associated with height loss. The adjusted odds ratio (OR) was 1.46 (95% confidence interval, 1.15, 1.83). Essentially the same associations were observed for men and women. The adjusted OR (95% CI) was 1.43 (1.01, 2.04) for men and 1.46 (1.07, 1.99) for women. Among older individuals, atherosclerosis is associated with height loss. This result can help clarify the mechanism underlying the association between height loss and cardiovascular disease.

A cross-sectional study exploring the relationship between oxidative balance score and 10-year atherosclerotic cardiovascular disease risk based on the National Health and Nutrition Examination Survey (2011-2020).

BACKGROUND: The intricate interaction between oxidative stress and atherosclerotic cardiovascular disease (ASCVD) is an essential area of research because of the potential role of oxidative homeostasis in regulating ASCVD risk. This study aimed to investigate the relationship between the oxidative balance score (OBS) and the 10-years risk of ASCVD to gain insight into how oxidative balance affects cardiovascular health. METHODS: This cross-sectional study analyzed National Health and Nutrition Examination Survey (NHANES) 2011-2020 data (40-79 age group), exploring OBS's link to 10-years ASCVD risk. OBS categorized dietary and lifestyle factors. Multivariate logistic regression controlled for age, sex, race, and demographics. A restricted cubic spline examined linear relationships; robustness was ensured through subgroup analyses. RESULTS: Analysis of 4955 participants reveals a negative association between OBS and 10-years ASCVD risk. Continuous OBS adjusted OR: 0.97 (95% CI: 0.95∼0.99, p < .001). Quartile analysis shows reduced risk in Q2 0.88 (95% CI: 0.63∼1.22, p = .43), Q3 0.92 (95% CI: 0.66∼1.28, p = .614), and Q4 0.59 (95% CI: 0.42∼0.83, p = .002) compare Q1. Quartile analysis indicated decreasing risk in higher OBS quartiles. Lifestyle OBS and Dietary OBS demonstrated similar trends. Stratified analyses highlight race and hypertension as effect modifiers (p < .05). CONCLUSION: Our study suggests an association between higher OBS and a reduced 10-years ASCVD risk. However, causation should not be inferred, and in the future, more extensive clinical and fundamental research is required to delve deeper into this association.

Online application for the diagnosis of atherosclerosis by six genes.

BACKGROUND: Atherosclerosis (AS) is a primary contributor to cardiovascular disease, leading to significant global mortality rates. Developing effective diagnostic indicators and models for AS holds the potential to substantially reduce the fatalities and disabilities associated with cardiovascular disease. Blood sample analysis has emerged as a promising avenue for facilitating diagnosis and assessing disease prognosis. Nonetheless, it lacks an accurate model or tool for AS diagnosis. Hence, the principal objective of this study is to develop a convenient, simple, and accurate model for the early detection of AS. METHODS: We downloaded the expression data of blood samples from GEO databases. By dividing the mean values of housekeeping genes (meanHGs) and applying the comBat function, we aimed to reduce the batch effect. After separating the datasets into training, evaluation, and testing sets, we applied differential expression analyses (DEA) between AS and control samples from the training dataset. Then, a gradient-boosting model was used to evaluate the importance of genes and identify the hub genes. Using different machine learning algorithms, we constructed a prediction model with the highest accuracy in the testing dataset. Finally, we make the machine learning models publicly accessible by shiny app construction. RESULTS: Seven datasets (GSE9874, GSE12288, GSE20129, GSE23746, GSE27034, GSE90074, and GSE202625), including 403 samples with AS and 325 healthy subjects, were obtained by comprehensive searching and filtering by specific requirements. The batch effect was successfully removed by dividing the meanHGs and applying the comBat function. 331 genes were found to be related to atherosclerosis by the DEA analysis between AS and health samples. The top 6 genes with the highest importance values from the gradient boosting model were identified. Out of the seven machine learning algorithms tested, the random forest model exhibited the most impressive performance in the testing datasets, achieving an accuracy exceeding 0.8. While the batch effect reduction analysis in our study could have contributed to the increased accuracy values, our comparison results further highlight the superiority of our model over the genes provided in published studies. This underscores the effectiveness of our approach in delivering superior predictive performance. The machine-learning models were then uploaded to the Shiny app's server, making it easy for users to distinguish AS samples from normal samples. CONCLUSIONS: A prognostic Shiny application, built upon six potential atherosclerosis-associated genes, has been developed, offering an accurate diagnosis of atherosclerosis.

Apolipoprotein B - An ideal biomarker for atherosclerosis?

This review article describes the pathophysiological mechanisms linking Apolipoprotein B (Apo-B) and atherosclerosis, summarizes the existing evidence on Apo B as a predictor of atherosclerotic cardiovascular disease and recommendations of (inter)national treatment guidelines regarding Apo B in dyslipidemia management. A single Apo B molecule is present in every particle of very low-density lipoprotein, intermediate density lipoprotein, low density lipoprotein, and lipoprotein(a). This unique single Apo B per particle ratio makes plasma Apo B concentration a direct measure of the number of circulating atherogenic lipoproteins. This review of global evidence on Apo B as a biomarker for atherosclerosis confirms that Apo B is a single atherogenic lipid marker present in all lipids sub-fractions except HDL-C, and thus, Apo B integrates and extends the information from triglycerides and cholesterol, which could simplify and improve care for atherosclerotic cardiovascular disease.

Evaluation of reducing the south and reinforcing the north method on postmenopausal atherosclerosis disease based on 4 diagnostic objectifications: A prospective observational study.

Reducing the south and reinforcing the north method (RSRN) has a positive effect on atherosclerosis disease. However, there is a lack of objective standards based on the quantification of 4 diagnostic methods in evaluating the improvement or effectiveness of the treatment. This study aimed to explore the quantitative evaluation of the therapeutic effect of RSRN on postmenopausal atherosclerosis based on the 4 diagnostic methods. The observational prospective cohort study was conducted at Longhua hospital Shanghai University of traditional Chinese medicine. According to the inclusion criteria, 96 patients (disease group) and 38 healthy cases (control group) were selected, the pulse parameters were compared between the 2 groups to demonstrate the reliability and success of the disease model. Then 4 diagnostic information before and after RSRN treatment were collected and statistical analyzed by 1-way analysis of variance (ANOVA) (with Bonferroni correction). Furthermore, social network analysis was used to analyze the changes of symptoms, tongue, pulse, and complexion characteristics before and after treatment. There was a significant difference in pulse parameters between the disease group and the control group. The pulse parameters t1, h3, h3/h1, h4/h1, S, As, and w values in disease group were higher than those in control group, while the h5, h5/h1, and Ad values were lower than those in control group (P < .05). After the treatment of RSRN, the clinical symptoms of patients were greatly improved. The facial color indexes L, a, b values of the disease group at week 6 were different from those at week 0 (P < .05). The overall brightness and chroma of the patient's facial color were significantly improved. The patients had virtual string pulse at week 0, and mainly string I and string II at week 7. The pulse parameters t1, t5, w, w/t, h1, h5, h3/h1, and h5/h1 values at week 7 were different from those at weeks 0, 1, 2 (P < .05); the tongue image was mainly red and crimson, peeling or greasy fur at week 0, while at weeks 6, 7, mainly light red, or thin white tongue. The RSRN method can regulate the complexion, tongue and pulse condition, clinical symptoms of postmenopausal atherosclerosis.

The Pathophysiologic Basis of Managing Chronic Atherosclerotic Cardiovascular Disease.

Chronic coronary heart disease encompasses a broad spectrum of disorders that range in severity from trivial to imminently life-threatening. The primary care physician encounters coronary disease at all stages. The number of available diagnostic and therapeutic options for evaluating and treating coronary disease is vast, presenting a complex selection strategy challenge when making choices for the individual patient. The primary care physician is responsible to tailor evaluation and management strategies to each individual patient based on his/her particular disease characteristics. There are many categories of diagnostic studies and therapeutic interventions that have been shown at the population level in clinical trials to improve patient outcomes. Blindly applying the findings of all demonstrated studies and therapies to a patient with coronary disease would saddle him/her with an unsustainable burden of diagnostic tests and therapies. The core principle of the approach outlined in this article is to tailor diagnostic and therapeutic choices to the operative pathophysiology that drives a particular patient's disorder. This introductory article is intended to provide a conceptual framework for studying and applying the specialized topics discussed in the articles that follow.

Multi-Ethnic Study of Atherosclerosis Early Heart Failure Study: Rationale, Design, and Baseline Characteristics.

BACKGROUND: Current prevalence estimates of heart failure (HF) are primarily based on self-report or HF hospitalizations. There is an unmet need to define the prevalence and pathogenesis of early symptomatic HF, which may be undiagnosed and precedes HF hospitalization. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) Early HF study was conducted during MESA exam 6 to determine the prevalence of early HF and investigate the transition from risk factors to early HF in a diverse population-based cohort of older adults. Between 2016 and 2018, 3285 MESA participants from 6 field centers underwent comprehensive speckle-tracking echocardiography with passive leg raise maneuver, Kansas City Cardiomyopathy Questionnaire, 6-minute walk test, arterial stiffness assessment, and proteomics (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]). RESULTS: Median age was 73 (25th-75th percentile 67-81) years, 53.2% were female, 25.6% were Black, 12.8% were Chinese, and 40.0% were White. The prevalence of HF risk factors was high: hypertension, 61.9%; former or current smoking, 53.7%; obesity 34.8%; diabetes; 24.7%; and chronic kidney disease; 22%. Overt cardiovascular disease, which ranged from 2.1% (HF) to 13.6% (atrial fibrillation), was less common. Of the 3285 participants, 96% underwent proteomics, 94% Kansas City Cardiomyopathy Questionnaire, 93% speckle-tracking echocardiography with passive leg raise, 82% arterial stiffness exam, and 77% 6-minute walk test. Feasibility of resting speckle-tracking echocardiography (87%-99% across cardiac chambers) and passive leg raise Doppler/speckle-tracking echocardiography (>84%) measurements was high. A total of 120 unique echocardiographic indices were measured. CONCLUSIONS: The MESA Early HF study is a key resource for cardiovascular researchers who are interested in improving the epidemiological and phenotypic characterization of early HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005487.

Causal association between helicobacter pylori and atherosclerosis: a two-sample Mendelian randomization.

BACKGROUND: Helicobacter pylori (H. pylori), according to a number of recent observational studies, is connected to atherosclerosis (AS). However, the link between H. pylori and AS is debatable. METHODS: In order to calculate the causal relationship between H. pylori and AS, we employed a two-sample Mendelian randomization (MR) analysis. The data for H. pylori were obtained from the IEU GWAS database ( https://gwas.mrcieu.ac.uk/datasets/ ) and the data for AS were obtained from the Finngen GWAS database ( https://r5.finngen.fi/ ). We selected single nucleotide polymorphisms with a threshold of 5 × 10-6 from earlier genome-wide association studies. MR was performed mainly using the inverse variance weighted (IVW) method. To ensure the reliability of the findings, We performed a leave-one-out sensitivity analysis to test for sensitivity. F-value was used to test weak instrument. RESULTS: A positive causal relationship between H. pylori OMP antibody levels and peripheral atherosclerosis was shown by our two-sample MR analysis (odds ratio (OR) = 1.33, 95% confidence interval (CI) = 1.14-1.54, P = 0.26E-03) using IVW. Additionally, there was a causative link between coronary atherosclerosis and H. pylori VacA antibody levels (IVW OR = 1.06, 95% CI = 1.01-1.10, P = 0.016). All the F-values were above 10. CONCLUSIONS: This MR study discovered a causal link between H. pylori and AS. Different antibodies have different effects, so future researches are needed to figure out the exact mechanisms behind this link.

An Atherosclerosis Indicator Hyaluronic Acid: Can Plasma Hyaluronic Acid Be Useful in Diagnosing Alzheimer's Disease?

BACKGROUND: The aim is to compare the plasma levels of hyaluronic acid (HA) which is closely related to inflam-mation and vascular changes and arterial stiffness (AS) related values in patients with Alzheimer's disease (AD), amnestic type mild cognitive impairment (aMCI), and normal cognitive functions (NCF). METHODS: Ninety participants were categorized into three groups, patients with AD, MCI, and NCF. Arterial stiffness measurement in the nephrology outpatient clinic, and storage and analysis of plasma samples in the biochemistry laboratory. RESULTS: Of the 90 patients, 32 had NCF, 32 had aMCI, and 26 had AD. Between groups, there was no difference in HA, pulse wave velocity, and augmentation index. The HA level had no statistically significant correlation with any of the other variables. CONCLUSIONS: Plasma HA levels will not be useful in the diagnosis of AD. More comprehensive studies with larger number of patients are needed.

[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.

Expression and diagnostic value of lncRNA MALAT1 and NLRP3 in lower limb atherosclerosis in diabetes.

OBJECTIVE: This study aimed to examine the diagnostic predictive value of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1(MALAT1) and NOD-like receptor protein 3(NLRP3) expression in patients with type 2 diabetes mellitus(T2DM) and lower extremity atherosclerosis disease (LEAD). METHODS: A total of 162 T2DM patients were divided into T2DM with LEAD group (T2DM + LEAD group) and T2DM alone group (T2DM group). The lncRNA MALAT1 and NLRP3 expression levels were measured in peripheral blood, and their correlation was examined. Least absolute shrinkage and selection operator (LASSO) regression model was used to screen for the best predictors of LEAD, and multivariate logistic regression was used to establish a predictive model and construct the nomogram. The effectiveness of the nomogram was assessed using the receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: The levels of the lncRNA MALAT1 and NLRP3 in the T2DM + LEAD group were significantly greater than those in the T2DM group (P <0.001), and the level of the lncRNA MALAT1 was positively correlated with that of NLRP3 (r = 0.453, P<0.001). The results of the LASSO combined with the logistic regression analysis showed that age, smoking, systolic blood pressure (SBP), NLRP3, and MALAT1 were the influencing factors of T2DM with LEAD(P<0.05). ROC curve analysis comparison: The discriminatory ability of the model (AUC = 0.898), MALAT1 (AUC = 0.804), and NLRP3 (AUC = 0.794) was greater than that of the other indicators, and the predictive value of the model was the greatest. Calibration curve: The nomogram model was consistent in predicting the occurrence of LEAD in patients with T2DM (Cindex = 0.898). Decision curve: The net benefit rates obtained from using the predictive models for clinical intervention decision-making were greater than those obtained from using the individual factors within the model. CONCLUSION: MALAT1 and NLRP3 expression increased significantly in T2DM patients with LEAD, while revealing the correlation between MALAT1 and NLRP3. The lncRNA MALAT1 was found as a potential biomarker for T2DM with LEAD.

Unlocking potential biomarkers bridging coronary atherosclerosis and pyrimidine metabolism-associated genes through an integrated bioinformatics and machine learning approach.

BACKGROUND: This study delves into the intricate landscape of atherosclerosis (AS), a chronic inflammatory disorder with significant implications for cardiovascular health. AS poses a considerable burden on global healthcare systems, elevating both mortality and morbidity rates. The pathological underpinnings of AS involve a marked metabolic disequilibrium, particularly within pyrimidine metabolism (PyM), a crucial enzymatic network central to nucleotide synthesis and degradation. While the therapeutic relevance of pyrimidine metabolism in diverse diseases is acknowledged, the explicit role of pyrimidine metabolism genes (PyMGs) in the context of AS remains elusive. Utilizing bioinformatics methodologies, this investigation aims to reveal and substantiate PyMGs intricately linked with AS. METHODS: A set of 41 candidate PyMGs was scrutinized through differential expression analysis. GSEA and GSVA were employed to illuminate potential biological pathways and functions associated with the identified PyMGs. Simultaneously, Lasso regression and SVM-RFE were utilized to distill core genes and assess the diagnostic potential of four quintessential PyMGs (CMPK1, CMPK2, NT5C2, RRM1) in discriminating AS. The relationship between key PyMGs and clinical presentations was also explored. Validation of the expression levels of the four PyMGs was performed using the GSE43292 and GSE9820 datasets. RESULTS: This investigation identified four PyMGs, with NT5C2 and RRM1 emerging as key players, intricately linked to AS pathogenesis. Functional analysis underscored their critical involvement in metabolic processes, including pyrimidine-containing compound metabolism and nucleotide biosynthesis. Diagnostic evaluation of these PyMGs in distinguishing AS showcased promising results. CONCLUSION: In conclusion, this exploration has illuminated a constellation of four PyMGs with a potential nexus to AS pathogenesis. These findings unveil emerging biomarkers, paving the way for novel approaches to disease monitoring and progression, and providing new avenues for therapeutic intervention in the realm of atherosclerosis.

Causality of the gut microbiome and atherosclerosis-related lipids: a bidirectional Mendelian Randomization study.

AIMS: Recent studies have indicated an association between intestinal flora and lipids. However, observational studies cannot indicate causality. In this study, we aimed to investigate the potentially causal relationships between the intestinal flora and blood lipids. METHODS: We performed a bidirectional two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between intestinal flora and blood lipids. Summary statistics of genome-wide association studies (GWASs) for the 211 intestinal flora and blood lipid traits (n = 5) were obtained from public datasets. Five recognized MR methods were applied to assess the causal relationship with lipids, among which, the inverse-variance weighted (IVW) regression was used as the primary MR method. A series of sensitivity analyses were performed to test the robustness of the causal estimates. RESULTS: The results indicated a potential causal association between 19 intestinal flora and dyslipidemia in humans. Genus Ruminococcaceae, Christensenellaceae, Parasutterella, Terrisporobacter, Parabacteroides, Class Erysipelotrichia, Family Erysipelotrichaceae, and order Erysipelotrichales were associated with higher dyslipidemia, whereas genus Oscillospira, Peptococcus, Ruminococcaceae UCG010, Ruminococcaceae UCG011, Dorea, and Family Desulfovibrionaceae were associated with lower dyslipidemia. After using the Bonferroni method for multiple testing correction, Only Desulfovibrionaceae [Estimate = -0.0418, 95% confidence interval [CI]: 0.9362-0.9826, P = 0.0007] exhibited stable and significant negative associations with ApoB levels. The inverse MR analysis did not find a significant causal effect of lipids on the intestinal flora. Additionally, no significant heterogeneity or horizontal pleiotropy for IVs was observed in the analysis. CONCLUSION: The study suggested a causal relationship between intestinal flora and dyslipidemia. These findings will provide a meaningful reference to discover dyslipidemia for intervention to address the problems in the clinic.

Severe hypoglycemia and hypoglycemia awareness are associated with preclinical atherosclerosis in patients with type 1 diabetes without an estimated high cardiovascular risk.

AIMS: To explore the relationship between severe hypoglycemia (SH) and hypoglycemia awareness with preclinical atherosclerosis in type 1 diabetes (T1D). MATERIALS AND METHODS: Cross-sectional study in patients with T1D without cardiovascular disease (CVD), and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of T1D duration with another risk factor. CVD risk was estimated with the Steno T1 Risk Engine (Steno-Risk). Carotid plaque was evaluated using standardised ultrasonography protocol. Logistic regression models adjusted for CVD risk factors were constructed to test the independent associations with SH or hypoglycemia awareness assessed by the Clarke questionnaire (Clarke). The inclusion of SH and Clarke in Steno-Risk was further evaluated. RESULTS: We included 634 patients (52.4% men, age 48.3 ± 10.8 years, T1D duration 27.4 ± 11.1 years, 39.9% harbouring plaque). A stepped increase in the presence of plaque according to Steno-Risk was observed (13.5%, 37.7%, and 68.7%, for low, moderate, and high risk, respectively; p < 0.001). SH history (OR 4.4 [1.3-14.6]) and Clarke score (OR 1.7 [1.2-2.2]) were associated with plaque in low-risk patients (n = 192). Clarke score was also associated with plaque burden in low-moderate-risk participants (n = 436; ≥2 plaques: OR 1.2 [1.0-1.5], p = 0.031; ≥3 plaques: OR 1.4 [1.1-2.0], p = 0.025). The inclusion of SH and Clarke scores in Steno-Risk significantly improved the identification of low-risk individuals with atherosclerosis (area under the curve: 0.658 vs. 0.576; p = 0.036). CONCLUSIONS: In patients with T1D without an estimated high CVD risk, SH and hypoglycemia awareness assessment score were independently associated with preclinical atherosclerosis and improved identification of patients who would benefit from an intensive approach.

Performance improvement of atherosclerosis risk assessment based on feature interaction.

BACKGROUND AND OBJECTIVE: Cardiovascular disease is a leading cause of mortality and premature death. Early intervention in asymptomatic individuals through risk assessment can reduce the incidence of disease. Atherosclerosis is a major cause of cardiovascular disease and early detection can effectively prevent and treat it. In this study, we used real patient data to evaluate the risk of atherosclerosis, assisting doctors in diagnosis and reducing the incidence of cardiovascular disease. METHODS: We proposed a multi-stage atherosclerosis risk assessment model that includes three main stages: (i) SMOTE and decorrelation weighting algorithm technology were added to the causal stability middle layer to address class imbalance in the dataset and reduce the impact of feature-induced dataset distribution shifts on model differences. (ii) The feature interaction layer considered possible feature interactions and classified features by different categories. By adding more effective feature information, the accuracy and generalizability of the model were improved. (iii) In the integrated model layer, we chose LightGBM as the decision tree integration model for risk assessment because it has higher accuracy and robustness compared to other machine learning algorithms. RESULTS: The final model used a dataset containing 21 original features and 17 interaction features, achieving excellent performance under a 10-fold cross-validation strategy. The macro accuracy reached 93.86%, macro precision was 94.82%, macro recall was 93.52%, and macro F1 score was as high as 93.37%. These indicators demonstrate the accuracy and robustness of the model in atherosclerosis risk assessment. CONCLUSION: The model provides strong support for the prevention and diagnosis of cardiovascular disease. Through atherosclerosis risk assessment, the model can help doctors develop personalized prevention and treatment plans, which is of great significance for the prevention and treatment of cardiovascular disease.

[DIAGNOSIS AND TREATMENT OF ELEVATED LIPOPROTEIN(A) IN ISRAEL: CONSENSUS STATEMENT FROM THE ISRAEL SOCIETY FOR RESEARCH, PREVENTION AND TREATMENT OF ATHEROSCLEROSIS AND ISRAEL SOCIETY FOR CLINICAL LABORATORY SCIENCES].

INTRODUCTION: Lipoprotein(a) [Lp(a)] is composed of 2 major protein components, a low-density lipoprotein (LDL) cholesterol-like particle containing apolipoprotein B (apo B) that is covalently bound to apolipoprotein(a). Its level is predominantly genetically determined, and it is estimated that 20% to 25% of the population have Lp(a) levels that are associated with increased cardiovascular risk. Elevated Lp(a) is related to increased vascular inflammation, calcification, atherogenesis and thrombosis, and is considered an independent and potentially causal risk factor for atherosclerotic cardiovascular diseases and calcified aortic valve stenosis. Recent data demonstrate that Lp(a) testing has the potential to reclassify patients' risk and improve cardiovascular risk prediction, and therefore could inform clinical decision-making regarding risk management. Statins and ezetimibe are ineffective in lowering Lp(a) levels, whereas proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have a modest effect on Lp(a) reduction. Nevertheless, RNA interference-based therapies with potent Lp(a)-lowering effects are in advanced stages of development, and clinical trials are underway to confirm their benefit in reducing cardiovascular events. This scientific consensus document was developed by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, and the Israeli Society for Clinical Laboratory Sciences, in order to create uniformity in Lp(a) measurement methods, indications for testing and reporting of the results, aiming to improve the diagnosis and management of elevated Lp(a) in clinical practice.

Spatial Metabolomics Identifies LPC(18:0) and LPA(18:1) in Advanced Atheroma With Translation to Plasma for Cardiovascular Risk Estimation.

BACKGROUND: The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each arterial tunica. We aimed first to identify, in a spatially resolved manner, the specific metabolic changes in plaque, media, adventitia, and cardiac tissue between control and atherosclerotic murine aortas. Second, we assessed their translatability to human tissue and plasma for cardiovascular risk estimation. METHODS: In this observational study, mass spectrometry imaging (MSI) was applied to identify region-specific metabolic differences between atherosclerotic (n=11) and control (n=11) aortas from low-density lipoprotein receptor-deficient mice, via histology-guided virtual microdissection. Early and advanced plaques were compared within the same atherosclerotic animals. Progression metabolites were further analyzed by MSI in 9 human atherosclerotic carotids and by targeted mass spectrometry in human plasma from subjects with elective coronary artery bypass grafting (cardiovascular risk group, n=27) and a control group (n=27). RESULTS: MSI identified 362 local metabolic alterations in atherosclerotic mice (log2 fold-change ≥1.5; P≤0.05). The lipid composition of cardiac tissue is altered during atherosclerosis development and presents a generalized accumulation of glycerophospholipids, except for lysolipids. Lysolipids (among other glycerophospholipids) were found at elevated levels in all 3 arterial layers of atherosclerotic aortas. LPC(18:0) (lysophosphatidylcholine; P=0.024) and LPA(18:1) (lysophosphatidic acid; P=0.025) were found to be significantly elevated in advanced plaques as compared with mouse-matched early plaques. Higher levels of both lipid species were also observed in fibrosis-rich areas of advanced- versus early-stage human samples. They were found to be significantly reduced in human plasma from subjects with elective coronary artery bypass grafting (P<0.001 and P=0.031, respectively), with LPC(18:0) showing significant association with cardiovascular risk (odds ratio, 0.479 [95% CI, 0.225-0.883]; P=0.032) and diagnostic potential (area under the curve, 0.778 [95% CI, 0.638-0.917]). CONCLUSIONS: An altered phospholipid metabolism occurs in atherosclerosis, affecting both the aorta and the adjacent heart tissue. Plaque-progression lipids LPC(18:0) and LPA(18:1), as identified by MSI on tissue, reflect cardiovascular risk in human plasma.

Polyvascular atherosclerosis and renal dysfunction increase the odds of cognitive impairment in vascular disease: findings of the LipidCardio study.

INTRODUCTION: Growing evidence suggests a causal role for atherosclerotic vascular disease in cognitive impairment and dementia. Atherosclerosis may present as monovascular disease (monoVD) or as widespread polyvascular atherosclerotic disease (polyVD). Evidence on the relationship between monoVD or polyVD and cognitive impairment is limited. METHODS: We conducted a cross-sectional analysis of baseline data from the LipidCardio Study. The main outcome measure was the presence of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score < 26. RESULTS: The mean age was 71.5 years, 30.3% were female, 17.3% had no evidence of large-vessel atherosclerosis, 71.1% had monoVD, and 11.7% had polyVD, defined as the presence of atherosclerosis in ≥ 2 vascular territories (coronary, cerebral, aortic, or lower extremity). A total of 21.6% had cognitive impairment according to the prespecified cutoff (MMSE < 26). Overall, the odds of cognitive impairment increased for each additional vascular territory affected by atherosclerosis [adjusted odds ratio 1.76, 95% confidence interval (CI) 1.21-2.57, p = 0.003]. Furthermore, there was evidence for an interaction between vascular disease and chronic kidney disease (CKD). The odds of cognitive impairment were not greater in the monoVD subgroup compared to those without any atherosclerosis, if CKD was absent (OR 0.98, 95% CI 0.48-2.10; p = 0.095), while the odds ratio (OR) of cognitive impairment with polyVD compared to no atherosclerosis was 2.71 (95% CI 1.10-6.92; p = 0.031). In contrast, in patients with CKD, both monoVD and polyVD were associated with significantly higher odds of cognitive impairment than no atherosclerosis. CONCLUSIONS: PolyVD is associated with increased odds of cognitive impairment. MonoVD is associated with cognitive impairment only in the presence of CKD.

Age and Aspirin Dosing in Secondary Prevention of Atherosclerotic Cardiovascular Disease.

BACKGROUND: In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease. METHODS AND RESULTS: In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow-up: 26.2 months; interquartile range: 19.0-34.9 months). Median age was 67.6 years (interquartile range: 60.7-73.6 years). Among participants aged <65 years (n=5841 [38.7%]), a primary end point occurred in 226 (7.54%) in the 81 mg group, and in 191 (6.80%) in the 325 mg group (adjusted hazard ratio [HR], 1.23 [95% CI, 1.01-1.49]). Among participants aged ≥65 years (n=9235 [61.3%]), a primary end point occurred in 364 (7.12%) in the 81 mg group, and in 378 (7.96%) in the 325 mg group (adjusted HR, 0.95 [95% CI, 0.82-1.10]). The age-dose interaction was not significant (P=0.559). There was no significant interaction between age and the randomized aspirin dose for the secondary effectiveness and the primary safety bleeding end points (P>0.05 for all). CONCLUSIONS: Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.