Progression Of Atherosclerotic Cardiovascular Disease Research Articles

The Effects of Statin Treatment on Serum Ferritin Levels: A Systematic Review and Meta-Analysis.

Background: Statins are the most widely used drugs for decreasing elevated serum LDL-cholesterol (LDL-C) and thus for the prevention of atherosclerotic cardiovascular disease (ASCVD), but they have also some pleiotropic effects, including anti-inflammatory properties. Atherosclerosis is a low-grade inflammatory disease, and elevated ferritin is considered to be one of the markers of inflammation. Since the results of studies on the effects of statins on serum ferritin levels are conflicting, this meta-analysis was performed. Methods: A literature search was performed using major electronic databases (MEDLINE/PubMed, Scopus, Embase, and ISI Web of Science) from inception up to 5 March 2022 to find studies evaluating the effect of different statins on serum ferritin levels. The effect size was determined using weighted mean differences (WMDs) and the corresponding 95% confidence intervals (CIs). Results: The meta-analysis of nine studies (1611 patients) analyzing the effects of statins on serum ferritin levels that were included showed a significant decrease in circulating ferritin levels caused by statins. The results did not suggest any significant association between the changes in concentrations of serum ferritin and the duration of treatment with statins. Conclusions: Statin therapy decreases the circulating concentrations of ferritin, which might be beneficial for the prevention and/or progression of ASCVD. This effect might be explained by the anti-inflammatory effects and maybe some other pleiotropic effects of statins and not by their lipid-lowering effects.

Low-density lipoprotein particles in atherosclerosis.

Among the diseases causing human death, cardiovascular disease (CVD) remains number one according to the World Health Organization report in 2021. It is known that atherosclerosis is the pathological basis of CVD. Low-density lipoprotein (LDL) plays a pivotal role in the initiation and progression of atherosclerotic CVD (ASCVD). LDL cholesterol (LDL-C) is the traditional biological marker of LDL. However, large numbers of patients who have achieved the recommended LDL-C goals still have ASCVD risk. In multiple prospective studies, LDL particle (LDL-P) is reported to be more accurate in predicting CVD risk than LDL-C. LDL-Ps differ in size, density and chemical composition. Numerous clinical studies have proved that the atherogenic mechanisms of LDL-Ps are determined not only by LDL number and size but also by LDL modifications. Of note, small dense LDL (sdLDL) particles possess stronger atherogenic ability compared with large and intermediate LDL subfractions. Besides, oxidized LDL (ox-LDL) is another risk factor in atherosclerosis. Among the traditional lipid-lowering drugs, statins induce dramatic reductions in LDL-C and LDL-P to a lesser extend. Recently, proprotein convertase subtilsin/kexin type 9 inhibitors (PCSK9i) have been demonstrated to be effective in lowering the levels of LDL-C, LDL-P, as well as CVD events. In this article, we will make a short review of LDL metabolism, discuss the discordance between LDL-C and LDL-P, outline the atherogenic mechanisms of action of LDL by focusing on sdLDL and ox-LDL, summarize the methods used for measurement of LDL subclasses, and conclude the advances in LDL-lowering therapies using statins and PCSK9i.

U-Shaped Relationship of Non-HDL Cholesterol With All-Cause and Cardiovascular Mortality in Men Without Statin Therapy.

BackgroundNon-HDL-C is well established causal risk factor for the progression of atherosclerotic cardiovascular disease. However, there remains a controversial pattern of how non-HDL-C relates to all-cause and cardiovascular mortality, and the concentration of non-HDL-C where the risk of mortality is lowest is not defined.MethodsA population-based cohort study using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Male participants without statin therapy were divided into the six groups according to non-HDL-C levels (<100, 100–129, 130–159, 160–189, 190–219, ≥220 mg/dl). Multivariable Cox proportional hazards models were conducted with a hazard ratio (HR) and corresponding 95% confidence interval (CI). To further explore the relationship between non-HDL-C and mortality, Kaplan–Meier survival curves, restricted cubic spline curves, and subgroup analysis were performed.ResultsAmong 12,574 individuals (average age 44.29 ± 16.37 years), 1,174(9.34%) deaths during a median follow-up 98.38 months. Both low and high non-HDL-C levels were significantly associated with increased risk of all-cause and cardiovascular mortality, indicating a U-shaped association. Threshold values were detected at 144 mg/dl for all-cause mortality and 142 mg/dl for cardiovascular mortality. Below the threshold, per 30 mg/dl increase in non-HDL-C reduced a 28 and 40% increased risk of all-cause (p < 0.0001) and cardiovascular mortality (p = 0.0037), respectively. Inversely, above the threshold, per 30 mg/dl increase in non-HDL-C accelerated risk of both all-cause mortality (HR 1.11, 95% CI 1.03–1.20, p = 0.0057) and cardiovascular mortality (HR 1.30, 95% CI 1.09–1.54, p = 0.0028).ConclusionsNon-HDL-C was U-shaped related to all-cause and cardiovascular mortality among men without statin therapy.

HIV and cardiovascular disease: the role of inflammation.

HIV and antiretroviral therapy (ART) use are linked to an increased incidence of atherosclerotic cardiovascular disease (ASCVD). Immune activation persists in ART-treated people with HIV (PWH), and markers of inflammation (i.e. IL-6, C-reactive protein) predict mortality in this population. This review discusses underlying mechanisms that likely contribute to inflammation and the development of ASCVD in PWH. Persistent inflammation contributes to accelerated ASCVD in HIV and several new insights into the underlying immunologic mechanisms of chronic inflammation in PWH have been made (e.g. clonal haematopoiesis, trained immunity, lipidomics). We will also highlight potential pro-inflammatory mechanisms that may differ in vulnerable populations, including women, minorities and children. Mechanistic studies into the drivers of chronic inflammation in PWH are ongoing and may aid in tailoring effective therapeutic strategies that can reduce ASCVD risk in this population. Focus should also include factors that lead to persistent disparities in HIV care and comorbidities, including sex as a biological factor and social determinants of health. It remains unclear whether ASCVD progression in HIV is driven by unique mediators (HIV itself, ART, immunodeficiency), or if it is an accelerated version of disease progression seen in the general population.

Lipid-lowering for the prevention of cardiovascular disease in the new era: A practical approach to combination therapy: Lipid-lowering and combination therapy

Low density lipoprotein-cholesterol (LDL-C) is the main etiologic factor for the development and progression of atherosclerotic cardiovascular disease (ASCVD) and LDL-C reduction is a central tenet of ASCVD treatment and prevention. Moreover, ASCVD risk reduction is proportional to the magnitude of LDL-C lowering. Recent European guidelines have recommended a goal of &lt;55 mg/dL (&lt;1.4 mmol/L) for patients at very-high cardiovascular risk, while the U.S. guideline considers an LDL-C ≥70 mg/dL (≤1.8 mmol/L) as a threshold to intensify therapy with the addition of a non-statin therapy to statins. To reach these lower LDL-C goals of &lt;55 mg/dL or &lt;70 mg/dL, combination therapy is necessary in the majority of these patients. Drug combinations, and in particular single-pill combinations, may substantially increase adherence to therapy. Adherence is essential for achieving a clinical benefit and, as many patients discontinue medications, the long-term adherence to lipid-lowering therapy represents a major issue in ASCVD prevention. Secondary prevention or high-risk primary prevention patients, such as those with familial hypercholesterolemia in whom maximally-tolerated statin doses alone would not be anticipated to sufficiently lower LDL-C, would benefit from combination therapy. In current clinical practice, statins with ezetimibe, statins plus PCSK9 inhibitors (with or without ezetimibe), and, most recently statins or ezetimibe with bempedoic acid are the most commonly used combination therapies for LDL-C-lowering. This review outlines the importance of using combination therapy for the achievement of LDL-C treatment

Arterial stiffness in rheumatoid arthritis: Current knowledge and future perspectivess

Rheumatoid arthritis (RA) is characterized by the excess cardiovascular risk that remains essentially unaltered despite current medical advances. The introduction of reliable markers towards early identification and subsequently effective management of high-risk patients with RA are urgently needed. Arterial stiffness represents an early indicator of cardiovascular morbidity and mortality and has emerged as a surrogate marker of cardiovascular disease. From a pathophysiological perspective, it is significantly accelerated by the accumulation of cardiovascular risk factors and is considered an intermediate process towards the development and progression of atherosclerotic cardiovascular disease. The aim of this review is to critically upraise current knowledge on arterial stiffness in patients with RA. Although not all studies concur, increased Pulse Wave Velocity (PWV) has been repeatedly reported in patients with RA. However, results need to be interpreted with caution as most studies enrolled patients with multiple cardiovascular risk factors and/or established cardiovascular disease, or with uncontrolled RA with high levels of systemic inflammation. Whether and to which extent increased arterial stiffness among patients with RA is associated with the disease per se, or rather represents the composite effect of hypertension and other classical cardiovascular risk factors, warrants further investigation. The impact of antirheumatic drugs on arterial stiffness is also discussed. Considering the well-established predictive value of increased PWV both in the general population and patients at high cardiovascular risk, future studies need to focus on the clinical utility of this surrogate risk marker specifically in patients with RA.

Bisphenol S exposure accelerates the progression of atherosclerosis in zebrafish embryo-larvae

Bisphenol S (BPS), widely utilized in manufacturing of daily necessities, is a toxicant with potential to induce atherosclerotic cardiovascular disease (ASCVD). However, the mode of action by which BPS exposure induces ASCVD remains unknown. Here, macrophages that were exposed to BPS in combination with oxidized low-density lipoprotein (oxLDL) exhibited enhanced formation of foam cells, a hallmark of ASCVD. Furthermore, zebrafish embryo-larvae were exposed to BPS (0, 1, 10 and 100 μg/L) for 15 days (d) and the characteristic symptoms of ASCVD including an inflammatory response, macrophage recruitment around blood vessels, and accumulation of oxLDL on vascular endothelium, were induced in 15-d larvae. After zebrafish were exposed to BPS for 45 d, BPS mobilized fatty acid metabolism and activated peroxisome proliferator-activated receptor signaling in larval liver, the hub of endogenous lipid metabolism, causing an increase in plasma LDL. Driven by high plasma LDL levels, the caudal artery of zebrafish larvae exhibited lipid accumulation and a thickened area with a large number of collagen fibers, accompanied by characteristic lesions, as well as hyperlipidemia, erythrocyte aggregation, thinner blood vessel walls and increased levels of leukocytes and thromboocytes in plasma. Our data demonstrate that BPS accelerates the progression of ASCVD using zebrafish embryo-larvae as a model.

The Importance of Lipoprotein Lipase Regulation in Atherosclerosis.

Lipoprotein lipase (LPL) plays a major role in the lipid homeostasis mainly by mediating the intravascular lipolysis of triglyceride rich lipoproteins. Impaired LPL activity leads to the accumulation of chylomicrons and very low-density lipoproteins (VLDL) in plasma, resulting in hypertriglyceridemia. While low-density lipoprotein cholesterol (LDL-C) is recognized as a primary risk factor for atherosclerosis, hypertriglyceridemia has been shown to be an independent risk factor for cardiovascular disease (CVD) and a residual risk factor in atherosclerosis development. In this review, we focus on the lipolysis machinery and discuss the potential role of triglycerides, remnant particles, and lipolysis mediators in the onset and progression of atherosclerotic cardiovascular disease (ASCVD). This review details a number of important factors involved in the maturation and transportation of LPL to the capillaries, where the triglycerides are hydrolyzed, generating remnant lipoproteins. Moreover, LPL and other factors involved in intravascular lipolysis are also reported to impact the clearance of remnant lipoproteins from plasma and promote lipoprotein retention in capillaries. Apolipoproteins (Apo) and angiopoietin-like proteins (ANGPTLs) play a crucial role in regulating LPL activity and recent insights into LPL regulation may elucidate new pharmacological means to address the challenge of hypertriglyceridemia in atherosclerosis development.

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention.

Systemic lupus erythematosus (SLE) carries a significant risk of cardiovascular disease (CVD). The prevalence of premature CVD is especially noteworthy because it occurs in premenopausal women with SLE who would otherwise have very low rates of CVD. While traditional risk factors likely play a role in development of CVD in the setting of SLE, they do not fully explain the excess risk. The pathogenesis of CVD in SLE is not fully understood, but the inflammatory nature of SLE is believed to be a key factor in accelerating atherosclerosis. Systemic inflammation may lead to an abnormal lipid profile with elevated triglycerides, total cholesterol, and low-density lipoprotein cholesterol and dysfunctional high-density lipoprotein cholesterol. Additionally, the inflammatory milieu of SLE plasma promotes endothelial dysfunction and vascular injury, early steps in the progression of atherosclerotic CVD. Despite the overall headway that has been achieved in treating lupus, innovative therapeutics specifically targeting the progression of atherosclerosis within the lupus population are currently lacking. However, there have been advancements in the development of promising modalities for diagnosis of subclinical atherosclerosis and detection of high CVD risk patients. Due to the significant impact of CVD on morbidity and mortality, research addressing prevention and treatment of CVD in SLE needs to be prioritized. This review explores the intricate interplay of SLE-specific properties that contribute to atherosclerosis and CVD within this population, as well as screening methods and possible therapies.

Zinc finger E-box binding homeobox 1 and atherosclerosis: New insights and therapeutic potential.

Zinc finger E-box binding homeobox 1 (ZEB1), an important transcription factor belonging to the ZEB family, plays a crucial role in regulating gene expression required for both normal physiological and pathological processes. Accumulating evidence has shown that ZEB1 participates in the initiation and progression of atherosclerotic cardiovascular disease. Recent studies suggest that ZEB1 protects against atherosclerosis by regulation of endothelial cell angiogenesis, endothelial dysfunction, monocyte-endothelial cell interaction, macrophage lipid accumulation, macrophage polarization, monocyte-vascular smooth muscle cell (VSMC) interaction, VSMC proliferation and migration, and T cell proliferation. In this review, we summarize the recent progress of ZEB1 in the pathogenesis of atherosclerosis and provide insights into the prevention and treatment of atherosclerotic cardiovascular disease.

Abstract 13422: Long Term Association of Low Density Lipoprotein Patterns With Coronary Artery Calcium and Atherosclerotic Cardiovascular Disease Events: Insights From HeartSCORE Study

Introduction: Low-density lipoprotein (LDL) cholesterol, a factor in progression of atherosclerotic cardiovascular disease (CVD), consists of sub-fractions with different sizes and densities in three patterns (A (large buoyant), B (small dense), AB (intermediate pattern). We examined the associations of LDL patterns with subclinical ASCVD and future events. Methods: Participants from the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were assessed for baseline lipid levels and LDL sub-fraction types by an ultracentrifugation method (vertical auto profile). Electron beam CT scans were obtained in a subset of individuals and coronary artery calcium (CAC) scores were calculated (Agatston method). Adjusted odds ratios and hazard ratios (95% CI) were calculated using logistic regression and Cox regression, respectively, to estimate the independent association between LDL sub-fractions and both; CAC and ASCVD events (MI, ischemic stroke, death), respectively. Results: Among 1884 eligible participants (mean [SD] age; 59[7.5]y, 65.8% women, 37.9% black), mean HDL-c, LDL-c and Triglycerides were 142.2[36.0]mg/dL, 58.2[14.9]mg/dL and 111.2[47.7]mmHg, respectively. Sub-fractions of LDL pattern A, B and AB were observed in 761(40%), 507(26.9%) and 616(32.7%) individuals. Over a follow up of ~16y, patterns B(1.98[1.22-3.21) and AB (1.54[1.00-2.38)] were independently associated with incident risk of CVD events (vs pattern A). When stratified by race and gender, pattern AB showed independent risk of incident CVD events and CAC presence among blacks and males (Table) . Conclusions: In this biracial cohort of middle-aged adults, LDL sub-fraction patterns B and AB showed a significantly higher risk of long-term CVD events. Pattern AB was also associated with positive CAC in blacks and males. Further studies are needed to investigate LDL patterns in CVD risk profiling based on race and gender.

Improvement initiative in LDL-C management in Saudi Arabia: A call to action.

PurposeAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the Saudi Arabia (KSA). Over the last decade dyslipidemia has been the predominant risk factor in KSA. The linear relationship between low density lipoprotein cholesterol (LDL-C) levels, a marker for dyslipidemia, and progression of ASCVD is well established. The objective of this paper is to to provide an overview of the burden of disease, outline current clinical practice guidelines (CPG), examine gaps in care, and provide actionable recommendations to prevent, diagnose, and treat dyslipidemia in KSA.ResultsSaudi Arabia has the highest prevalence of ASCVD in the Gulf region. Several gaps in the implementation of CPGs, including the underdiagnosis and undertreatment of dyslipidemia, inadequate primary and secondary prevention efforts, complicated by a fragmented health system have been identified. Compelling evidence indicates that target LDL-C levels are not achieved throughout the Middle East region. In addition, high-risk patients are often left unidentified with adequate treatment.ConclusionThis statement recommends specific multilevel interventions to optimize the prevention, diagnosis, and treatment of ASCVD. These recommendations focus on strengthening primary and secondary prevention through education initiatives, establishment of specialized prevention and treatment centers, and development of local and regional CPGs.

Therapeutic Apheresis for Management of Lp(a) Hyperlipoproteinemia.

High lipoprotein(a) (Lp(a)) level is an independent cardiovascular risk factor with higher prevalence among patients with atherosclerotic cardiovascular disease (ASCVD). The actual problem is that most currently available lipid-lowering drugs are unable to abolish Lp(a) pathogenicity. Lipoprotein apheresis (LA) is an effective method for elimination of atherogenic lipoproteins, but it is approved only in some countries for treatment of elevated Lp(a) level in the presence of progressive ASCVD. In recent years, new studies on LA were published and the purpose of this review is to present the information on optimal management of Lp(a) hyperlipoproteinemia by LA in the modern era. Most clinical studies designed to treat Lp(a) hyperlipoproteinemia with different LA systems are small in size but demonstrate that the elimination of Lp(a) from bloodstream leads to reduction of inflammatory and prothrombotic process in a few months and to atherosclerotic plaques regression in 1.5years. Treatment with LA for 2 to 5years in terms of clinical trials and in real-world setting provides further evidence that Lp(a) reduction by 60-80% is associated with proportional decreasing of rate and risk of cardiovascular events. Specific Lp(a) apheresis is the only possible method that solely targets Lp(a). In most countries, non-specific LA is used for treatment Lp(a) hyperlipoproteinemia in very high-risk subjects with progressive ASCVD. PCSK9 inhibitors have only modest effect on significantly elevated Lp(a), whereas large population-based studies requested sustained and prolonged reduction of Lp(a) levels by 50-100mg/dL to gain proportional decreasing of major adverse cardiovascular events.

Should Lipoprotein(a) be Measured in Youth?

Should Lipoprotein(a) be Measured in Youth?

The role of interferon-γ in cardiovascular disease: an update.

Cardiovascular disease (CVD) is the leading cause of death, globally, and its prevalence is only expected to rise due to the increasing incidence of co-morbidities such as obesity and diabetes. Medical treatment of CVD is directed primarily at slowing or reversing the underlying atherosclerotic process by managing circulating lipids with an emphasis on control of low-density lipoprotein (LDL) cholesterol. However, over the past several decades, there has been increasing recognition that chronic inflammation and immune system activation are important contributors to atherosclerosis. This shift in focus has led to the elucidation of the complex interplay between cholesterol and cellular secretion of cytokines involved in CVD pathogenesis. Of the vast array of cytokine promoting atherosclerosis, interferon (IFN)-γ is highly implicated and, therefore, of great interest. Literature review was performed to further understand the effect of IFN-γ on the development of atherosclerotic CVD. IFN-γ, the sole member of the type II IFN family, is produced by T cells and macrophages, and has been found to induce production of other cytokines and to have multiple effects on all stages of atherogenesis. IFN-γ activates a variety of signaling pathways, most commonly the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, to induce oxidative stress, promote foam cell accumulation, stimulate smooth muscle cell proliferation and migration into the arterial intima, enhance platelet-derived growth factor expression, and destabilize plaque. These are just a few of the contributions of IFN-γ to the initiation and progression of atherosclerotic CVD. Given the pivotal role of IFN-γ in the advancement of CVD, activation of its signaling pathways is being explored as a driver of atherosclerosis. Manipulation of this key cytokine may lead to novel therapeutic avenues for CVD prevention and treatment. A number of therapies are being explored with IFN-γ as the potential target.

Adherence to Guideline Medication Recommendations to Prevent Atherosclerotic Cardiovascular Disease Progression Among Adults With Prior Myocardial Infarction

This cohort study describes the use of drug therapies to prevent the progression of atherosclerotic cardiovascular disease in US patients with prior myocardial infarction and elevated low-density lipoprotein cholesterol levels.

Relapsing and Progressive Complications of Severe Hypertriglyceridemia: Effective Long-Term Treatment with Double Filtration Plasmapheresis

Background: Severe hypertriglyceridemia (HTG) is associated with major complications such as acute or relapsing pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Rapid elimination of triglyceride (TG)-rich lipoproteins (LP) with double filtration plasmapheresis (DFPP) without need for substitution has been found to be effective for the acute, short-term treatment of HTG-induced AP. Data on the long-term use of DFPP to prevent HTG-associated complications are scarce. Objectives: To evaluate the use and efficacy of regular DFPP treatment in clinical practice for preventing recurrence of HTG-associated complications in thera­py refractory patients. Methods: Retrospective multicenter study in patients with severe symptomatic drug and diet refractory HTG with regular DFPP treatment. Patients’ incidence of HTG-associated pancreatic or cardiovascular complications was compared before treatment and with regular DFPP treatment. Results: Ten patients (3 female) were identified with baseline maximal TG concentrations of 2,587–28,090 mg/dL (median 5,487 mg/dL; interquartile range [IQR] 4,340–12,636). The mean observation period was 3.9 ± 3.4 years before and 3.8 ± 3.0 years after commencement of DFPP. In 5 patients, severe HTG was related to chylomicronemia, 2 patients had familial partial lipodystrophy Dunnigan, and 1 patient had additional LP(a)-hyperlipoproteinemia. The main HTG-associated complication was recurrent AP in 8 patients, including 1 patient treated during pregnancy. Two patients presented severe progressive ASCVD. With long-term DFPP treatment, the annual rate of HTG-associa­ted pancreatic or cardiovascular complications declined from median 1.4 (IQR 0.7–2.6) to 0 (IQR 0.0–0.4; p < 0.005). The absolute number of events was reduced by 77%. In 6 patients (60%) episodes of AP did not occur, nor was progression of ASCVD detected clinically or by routine imaging techniques. DFPP was effective in the elimination of TG-rich LP from plasma, and was safe and well-tolerated. Conclusion: Long-term, regular DFPP treatment resulted in stabilization of patients with severe HTG and related recurrent AP or progression of ASCVD, who were refractory to conventional dietary and drug therapy.

Targeting cardiovascular inflammation: next steps in clinical translation.

Systemic vascular inflammation plays multiple maladaptive roles which contribute to the progression and destabilization of atherosclerotic cardiovascular disease (ASCVD). These roles include: (i) driving atheroprogression in the clinically stable phase of disease; (ii) inciting atheroma destabilization and precipitating acute coronary syndromes (ACS); and (iii) responding to cardiomyocyte necrosis in myocardial infarction (MI). Despite an evolving understanding of these biologic processes, successful clinical translation into effective therapies has proven challenging. Realizing the promise of targeting inflammation in the prevention and treatment of ASCVD will likely require more individualized approaches, as the degree of inflammation differs among cardiovascular patients. A large body of evidence has accumulated supporting the use of high-sensitivity C-reactive protein (hsCRP) as a clinical measure of inflammation. Appreciating the mechanistic diversity of ACS triggers and the kinetics of hsCRP in MI may resolve purported inconsistencies from prior observational studies. Future clinical trial designs incorporating hsCRP may hold promise to enable individualized approaches. The aim of this Clinical Review is to summarize the current understanding of how inflammation contributes to ASCVD progression, destabilization, and adverse clinical outcomes. We offer forward-looking perspective on what next steps may enable successful clinical translation into effective therapeutic approaches-enabling targeting the right patients with the right therapy at the right time-on the road to more individualized ASCVD care.

Epicardial Adipose Tissue, Adiponectin and Leptin: A Potential Source of Cardiovascular Risk in Chronic Kidney Disease.

The importance of cardiometabolic factors in the inception and progression of atherosclerotic cardiovascular disease is increasingly being recognized. Beyond diabetes mellitus and metabolic syndrome, other factors may be responsible in patients with chronic kidney disease (CKD) for the high prevalence of cardiovascular disease, which is estimated to be 5- to 20-fold higher than in the general population. Although undefined uremic toxins are often blamed for part of the increased risk, visceral adipose tissue, and in particular epicardial adipose tissue (EAT), have been the focus of intense research in the past two decades. In fact, several lines of evidence suggest their involvement in atherosclerosis development and its complications. EAT may promote atherosclerosis through paracrine and endocrine pathways exerted via the secretion of adipocytokines such as adiponectin and leptin. In this article we review the current knowledge of the impact of EAT on cardiovascular outcomes in the general population and in patients with CKD. Special reference will be made to adiponectin and leptin as possible mediators of the increased cardiovascular risk linked with EAT.

Anti-inflammatory therapy in atherosclerosis.

Cardiovascular disease (CVD) is the leading cause of death. Although once considered merely as a lipid storage disease, studies indicate the role of inflammation in initiation and progression of atherosclerotic CVD, as well as the development of thrombotic complications. Despite significant advances in treatment of atherosclerosis, there still exists a residual risk for CVD-related morbidity and mortality. Even with optimal treatment, the rate of a new event after an index acute coronary syndrome event, such as myocardial ischemia or infarction, in the first three years has been reported to be as high as 20%. In the last decades, inflammation due to apoB-lipoproteins and other traditional risk factors, such as hypertension, diabetes and smoking, is accepted as a new target for CVD prevention. Up to now, several anti-inflammatory drugs have been tested for use in atherosclerosis. This review focuses on the current status of anti-inflammatory drug therapy for atherosclerotic CVD in humans.