The Role of Shear Stress in Coronary Artery Disease.

Coronary artery disease is the leading cause of morbidity and mortality worldwide, especially in developed countries, with an increasing incidence in developing countries. Despite the advances in cardiology, there are yet many unanswered questions about the natural history of coronary atherosclerosis. However, it has not been fully explained why some coronary artery plaques remain quiescent over time, whereas others evolve to a high-risk, "vulnerable" plaque with a predisposition to destabilize and induce a cardiac event. Furthermore, approximately half of the patients with acute coronary syndromes demonstrate no prior symptoms of ischemia or angiographically evident disease. Recent findings have indicated that apart from cardiovascular risk factors, genetics, and other unknown factors, local hemodynamic forces, such as endothelial shear stress, blood flow patterns, and endothelial dysfunction of the epicardial and microvascular coronary arteries, are associated with the progression of coronary plaque and the development of cardiovascular complications with complex interactions. In this review article, we summarize the mechanisms that affect coronary artery plaque progression, indicating the importance of endothelial shear stress, endothelial dysfunction of epicardial and microvascular vessels, inflammation, and their complex associations, underlying in parallel the clinical perspectives of these findings.

The prognostic role of galectin-3 and endothelial function in patients with heart failure.

BACKGROUND: Heart failure (HF) is nowadays classified as HF with reduced ejection fraction (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF). Endothelial dysfunction (assessed by flow-mediated dilatation [FMD]), increased arterial stiffness (assessed by carotid-femoral pulse-wave velocity [PWV]), and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF. METHODS: In this study we prospectively enrolled 340 patients with stable ischemic HF. We assessed the brachial artery FMD, carotid-femoral PWV, and galectin-3 levels, and patients were followed up for MACE according to HF group. RESULTS: Interestingly, the FMD values exhibited a stepwise improvement according to left ventricular ejection fraction (LVEF) (HFrEF: 4.74 ± 2.35% vs. HFmrEF: 4.97 ± 2.81% vs. HFpEF: 5.94 ± ± 3.46%, p = 0.01), which remained significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors, and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% confidence interval: 0.166-1.814, p = 0.019). Single-vessel coronary artery disease was more frequent in the group of HFpEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p = 0.049). PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51 ± 2.35% vs. 5.32 ± 2.67%, p = 0.02), and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p = 0.01). CONCLUSIONS: Flow-mediated dilatation displayed a linear improvement with LVEF in patients with ischemic HF. Deteriorated values are associated with MACE. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF.

Association of Growth Differentiation Factor 15 with Arterial Stiffness and Endothelial Function in Subpopulations of Patients with Coronary Artery Disease: A Proof-of-Concept Study.

BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a biomarker belonging to the transforming growth factor-beta cytokine superfamily, which is linked to many pathological conditions, including inflammation and myocardial injury. Pulse wave velocity (cfPWV) and augmentation index (AIx) are indices of arterial stiffness, which are associated with the severity of coronary artery disease (CAD). Flow-mediated dilatation (FMD) is a well-studied surrogate marker of endothelial-dependent dysfunction and systemic inflammation. OBJECTIVE: In this proof-of-concept study, we aimed to investigate the relationship between circulating GDF-15, endothelial dysfunction, and indices of arterial stiffness in different settings of coronary artery disease and myocardial injury. METHODS: In this cross-sectional single-center study, we enrolled patients (n = 22) after interventional treatment for acute myocardial infarction (AMI), patients (n = 11) admitted with chest pain and elevated cardiac enzymes but without evidence of obstructing CAD (MI-NOCAD) in percutaneous coronary angiography (CAG), and patients (n = 20) who underwent CAG according to indications without evident obstructive CAD in CAG (NOCAD). FMD was assessed at the brachial artery. AIx of the central aortic pressure and cfPWV were estimated by applanation tonometry at the radial and carotid-femoral site, respectively, with a validated acquisition system (Sphygmo- Cor, AtCor Medical, Sydney (NSW), Australia). ELISA was used to determine circulating GDF- 15 serum levels (R&D Systems, Minneapolis, MN). Clinical and demographic data and values of routine biochemical biomarkers were obtained. The highest high-sensitive cardiac Troponin I (hsTpnI) value during hospitalization was also recorded. Left ventricular ejection fraction (LVEF) was assessed with a transthoracic echocardiogram. RESULTS: Patients with AMI were older, had worse LVEF, higher values of hsTpnI and increased circulating GDF-15 levels. Importantly, AMI patients had increased cfPWV values, deteriorated AIx values, blunted FMD and worse serum creatinine levels compared to MI-NOCAD and NOCAD patients, respectively, whereas MI-NOCAD and NOCAD did not differ from each other significantly on these biomarkers. Both AMI and MI-NOCAD patients presented a higher but comparable white blood cell count than NOCAD patients. A strong linear correlation between GDF-15 and cfPWV, hsTpnI, AIx, white blood cell count and creatinine but not with FMD was demonstrated in the general study population. CONCLUSION: This proof-of-concept study showed that higher circulating levels of GDF-15, an inflammatory biomarker, were associated significantly with increased arterial stiffness only in AMI patients, whereas elevated GDF-15 demonstrated a linear relationship with the severity of the myocardial injury.

Lipoprotein-associated phospholipase A2 levels, endothelial dysfunction and arterial stiffness in patients with stable coronary artery disease.

BACKGROUND: Lipoprotein-associated Phospholipase A2 (Lp-PLA2), can exert proinflammatory as well as proatherogenic properties on the vascular wall. The current study sought to evaluate the influence of high Lp-PLA2 levels on indices of arterial wall properties in patients with stable coronary artery disease (CAD). METHODS: Three hundred seventy-four consecutive patients with stable CAD (mean age 61 ± 11 years, 89% males) were enrolled in this single-center cross-sectional study. Flow-mediated dilation (FMD) was used to assess endothelial function and augmentation index (AIx) of the central aortic pressure was used to assess reflected waves. ELISA was used to determine Lp-PLA2 serum levels. RESULTS: After dividing the participants in 3 equal groups based on the tertiles of circulating Lp-PLA2 values, no significant differences were demonstrated between those in the 3rd tertile with Lp-PLA2 values > 138 µg/L, in the 2nd tertile with Lp-PLA2 values between 101 and 138 µg/L and in the 1st tertile (Lp-PLA2 values < 101 µg/L) regarding age, male gender, smoking habits, family history of CAD or history of a previous myocardial infarction, diabetes mellitus, arterial hypertension, hyperlipidemia, duration of CAD and treatment with relevant medication. Importantly, subjects with Lp-PLA2 values in the highest tertile, had significantly reduced FMD values compared to the middle and lower tertile (4.43 ± 2.37% vs. 4.61 ± 1.97% vs. 5.20 ± 2.52% respectively, P = 0.03). Patients in the highest tertile of Lp-PLA2 values had significantly higher AIx values (24.65 ± 8.69% vs. 23.33 ± 9.65%, P = 0.03), in comparison to the lowest tertile, with Lp-PLA2 values < 101 µg/L. A linear regression analysis showed that Lp-PLA2 values > 138 µg/L negatively correlated to FMD [b = - 0.45 (95% CI: - 0.79 - -0.11), P = 0.01] and AIx values [b = 1.81 (95% CI: 0.57-3.05), P < 0.001] independently of cofounders like gender, age, diabetes mellitus, arterial hypertension, dyslipidemia, smoking habits, family history of CAD, history of previous myocardial infarction, serum glucose, circulating lipid levels, duration of CAD, antihypertensive medication, antidiabetic drugs, statin therapy and treatment with ß-blockers. CONCLUSIONS: Elevated Lp-PLA2 levels relate to endothelial dysfunction and arterial stiffness in patients with stable CAD independently from classical risk factors for CAD, statin use, antihypertensive treatment, and duration of the disease.

High-Intensity Endurance and Strength Training in Water Polo Olympic Team Players: Impact on Arterial Wall Properties.

INTRODUCTION: Regular physical activity is recommended to minimize health risk. However, the upper intensity threshold associated with the best health outcomes is difficult to be determined. Water polo (WP) Olympic athletes present unique characteristics such as high-intensity exercise, long training sessions, and a combination of endurance and strength training. Therefore, we examined in which way the long-term, intense, mixed endurance and strength training affects the peripheral and central hemodynamics. METHODS: The study population consisted of 20 WP Olympic team players, 20 matched recreationally active (RA) subjects, and 20 sedentary control subjects (Cl). Reflected waves were assessed with the augmentation index (AIx), central aortic stiffness with pulse wave velocity (PWV), and endothelial function with flow-mediated dilation (FMD). RESULTS: Amongst Cl subjects, RA subjects, and WP players, there was no difference in age (p = 0.33) as well as in brachial systolic pressure (p = 0.52), while there was a stepwise decrease in aortic systolic pressure (116 ± 16 mm Hg vs. 107 ± 14 mm Hg vs. 106 ± 6 mm Hg, p = 0.03). There was also a stepwise improvement in AIx (-4.22 ± 9.97% vs. -6.97 ± 11.28% vs. -12.14 ± 6.62%, p = 0.03) and FMD (6.61 ± 1.78% vs. 7.78 ± 1.98% vs. 8.3 ± 2.05%, p = 0.04) according to the intensity of exercise, with WP players having lower AIx and higher FMD compared to RA subjects and Cl subjects. No difference was found in PWV (Cl: 5.88 ± 0.72 m/s vs. RA: 6.04 ± 0.75 m/s vs. WP: 5.97 ± 1.09 m/s, p = 0.82) among the three studied groups. CONCLUSIONS: Young WP Olympic team players depict improved arterial wall properties and endothelial function compared to RA and Cl subjects.

Coronary Artery Disease and Endothelial Dysfunction: Novel Diagnostic and Therapeutic Approaches.

Coronary artery disease is the leading cause of morbidity and mortality worldwide. The most common pathophysiologic substrate is atherosclerosis which is an inflammatory procedure that starts at childhood and develops throughout life. Endothelial dysfunction is associated with the initiation and progression of atherosclerosis and is characterized by the impaired production of nitric oxide. In general, endothelial dysfunction is linked to poor cardiovascular prognosis and different methods, both invasive and non-invasive, have been developed for its evaluation. Ultrasound evaluation of flow mediated dilatation of the branchial artery is the most commonly used method to assessed endothelial function while intracoronary administration of vasoactive agents may be also be used to test directly endothelial properties of the coronary vasculature. Endothelial dysfunction has also been the subject of therapeutic interventions. This review article summarizes the knowledge about evaluation of endothelial function in acute coronary syndromes and stable coronary artery disease and demonstrates the current therapeutic approaches against endothelial dysfunction.

The Predictive Role for ST2 in Patients with Acute Coronary Syndromes and Heart Failure.

Intensive research has shed light on the utilization of novel biomarkers which facilitate the diagnosis and prognosis of patients with different medical problems. One of the most important biomarkers especially in the spectrum of heart failure is soluble ST2 (sST2: soluble Suppression of Tumorigenicity 2), which is involved in inflammation, fibrosis and cardiac stress. In the revised 2017 ACC/AHA/HFSA, "Focused Update Guidelines for the Management of Heart Failure" ST2 was given a class-IIa recommendation for the optimal risk assessment in patients with heart failure. Many studies indicate that not only baseline but also serial measurements of ST2 can accurately predict future cardiovascular events in patients with Acute Coronary Syndromes and heart failure. Therefore, in this review, we are going to discuss the studies about the prognostic significance of ST2 in patients with Acute Coronary Syndromes, acute and chronic heart failure.

Atrial Fibrillation: Biomarkers Determining Prognosis.

Atrial fibrillation (AF) is a common cardiac arrhythmia known to incite increased thromboembolic and mortality risks, especially among patients not under anticoagulant therapy when indicated. Several routine scores exist to help stratify AF patients, such as the CHAD2DS2-VASc score and upon which physicians are based to decide whether to administer anticoagulant therapy. Being that anticoagulant regimen is a double- edged situation with both benefits and risks, decision-making process demands a definite and reliable, evidence-based set of data to rely on. Blood-based biological elements known as biomarkers are measurable indices that can provide crucial insights concerning not only underlying disease mechanisms but also prognostic and risk stratifying information. As AF is constituted by an overwhelming range of pathophysiological aspects such as inflammation, fibrosis, hypercoagulable states and myocardial damage, identifying and assessing relevant biomarkers will evidently support the clinician's prognostication efforts. The current reviewpresents studied biomarkers with proven prognostic potential in AF as well as possible enhancement of risk-scores when incorporated to them.

The Impact of Omega 3 Fatty Acids in Atherosclerosis and Arterial Stiffness: An Overview of their Actions.

BACKGROUND: Fatty acids are common dietary nutrients particularly in economically developed countries. Research has revealed that omega-3fatty acids exert beneficial effects in the progression of atherosclerosis and cardiovascular disease. Moreover, eicosapentaenoic acid and docosahexaenoic acid possess a number of biological actions which improve cardio-metabolic health. Omega-3 fatty acids display remarkable anti-oxidant, anti-inflammatory, anti-thrombotic and anti-arrhythmogenic actions. Furthermore, they improve the levels of triglycerides, glucose metabolism and endothelial function. METHODS: The aim of this review article is to present physical, biochemical and biological properties of omega-3 fatty acids and summarize the most important mechanisms of action on arterial wall properties and arterial stiffness in atherosclerosis. RESULTS: Omega-3 fatty acids may prevent the progression of atherosclerosis. Endothelial dysfunction and arterial stiffness can be regulated by the supplementation of omega-3 fatty acids. CONCLUSION: The mechanisms of action of omega-3 fatty acids on cardiovascular health and arterial stiffening have been established. However, further research is needed in order to translate the conflicting results among the studies and improve the therapeutic options of cardiovascular disease.

Prognostic significance of arterial stiffness and osteoprotegerin in patients with stable coronary artery disease.

BACKGROUND: Arterial stiffness and vascular calcification significantly contribute to coronary atherosclerosis progression. The prognostic value of increased arterial stiffness and vascular calcification in subjects with stable coronary artery disease (CAD) after percutaneous coronary intervention(PCI) is currently under question. MATERIALS AND METHODS: We randomly enrolled 262 patients with stable CAD 1 month after successful PCI. Carotid-femoral pulse wave velocity (PWV) was measured as a well-established index of central aortic stiffness. Osteoprotegerin (OPG) plasma levels were measured as a biomarker of vascular calcification. Patients were followed up prospectively up to 52 months. The primary endpoint was the composite of death from cardiovascular causes, myocardial infarction, stroke or hospitalization for cardiovascular causes. RESULTS: During the follow-up period, 48 patients presented the primary composite endpoint. Subjects who presented the primary endpoint, compared to subjects free of cardiovascular events, had significantly increased PWV (9.45 ± 2.19 m/s vs 8.73 ± 2.07 m/s, P = .04) and OPG levels (4.21 ± 2.19 pmol/L vs 3.18 ± 1.74 pmol/L, P = .003). Survival analysis indicated that PWV predicted adverse cardiac events MACE (Hazard ratio = 1.29 95%CI: 1.07-1.57, P = .008) independently from confounders such as age, sex, smoking habits, ejection fraction, extent of coronary artery disease, hypertension and diabetes mellitus. Interestingly, for every increase in pulse wave velocity by 1 m/s, there is an anticipated increase in the risk of major adverse cardiovascular event (MACE) by 29%. CONCLUSIONS: These findings extend the current knowledge concerning the role of arterial stiffness as powerful biomarkers in cardiovascular disease. Measurement of PWV might have a role in ascertaining prognosis and managing treatment in patients with stable CAD after PCI.

Statins in aortic disease.

BACKGROUND: Numerous studies indicate that statins have also multiple beneficial actions (known as 'pleiotropic actions') on cardiovascular system through the improvement of endothelial dysfunction, inflammation, oxidative stress, increased arterial thrombosis, and the stabilization of the atherosclerotic plaque. Aortic disease primarily consists of aortic valve stenosis, aortic valve regurgitation, aneurysm disease, and genetic disorders such as Marfan syndrome, bicuspid aortic valve and aortic coarctation. Many studies have revealed the cardio-protective actions of statins in aortic disease. OBJECTIVE: Our aim was to present current data concerning present status of treatment with statins in aortic diseases. METHODS: A thorough search of PubMed and the Cochrane Database was conducted in order to identify the majority of studies and novel articles related to their use in aortic disease. RESULTS: Numerous studies in animals and humans indicate a beneficial effect of treatment with statins in the previous conditions apart from a few conflicting data. CONCLUSION: There is a need of further investigation in this field, especially for the estimation of the optimal type and dose of statins required in each clinical condition of aortic disease.

Genotyping, Platelet Activation, and Cardiovascular Outcome in Patients after Percutaneous Coronary Intervention: Two Pieces of the Puzzle of Clopidogrel Resistance.

OBJECTIVES: Individual platelet responses to antiplatelet therapy depend on genetic, cellular, and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet responses to antiplatelet treatment. We aimed to evaluate the impact of CYP2C19 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) on clopidogrel treatment. METHODS: We enrolled 408 patients with stable coronary artery disease (CAD) receiving aspirin and clopidogrel (75 mg/day) 1 month after PCI. High on-treatment platelet reactivity was evaluated using the VerifyNow Assay in a subset of patients. CYP2C19*2 and C34T P2Y12 genotyping was performed by real-time polymerase chain reaction. The primary end point was the composite of death or hospitalization for cardiovascular causes, and patients were followed for a median time of 13 months. RESULTS: In the total study population, 37% were carriers of at least 1 CYP2C19*2 loss-of-function allele, and 53% were carriers of at least 1 C34T loss-of-function allele. Interestingly, homozygotes of the CYP2C19*2 loss-of-function allele had significantly increased P2Y12 reaction units (PRU) (p = 0.007). However, PRU did not differ between carriers and noncarriers of the C34T loss-of-function allele (p = 0.41). Moreover, carriers of CYP2C19*2 had an increased hazard ratio (HR) for the occurrence of the primary end point (for carriers HR = 1.96, 95% CI 1.05-3.66, p = 0.03), whereas the C34T polymorphism had no impact on the cardiovascular outcome (p = 0.17). Finally, PRU was associated with cardiovascular outcome even after adjustment for the presence of any reduced function allele polymorphism. CONCLUSIONS: We documented a different effect of CYP2C19 and P2Y12 receptor polymorphisms on platelet reactivity and cardiovascular outcome in CAD patients after PCI on clopidogrel treatment. Importantly, increased platelet reactivity adversely affects the cardiovascular outcome independently of the studied polymorphisms.

Genetics in the Clinical Decision of Antiplatelet Treatment.

BACKGROUND: Coronary artery disease remains the leading cause of death globally. Dual antiplatelet treatment with aspirin and aP2Y12 receptor significantly reduces thrombotic events. However, antiplatelet drug response displays considerable interindividual variability. METHODS: Genetic factors account for up to 70% of impaired drug response. A number of genes encoding proteins involved in the pharmacokinetic pathway have been found to alter drug response. RESULTS: According to most studies, CYP2C19 gene is the strongest genetic determinant. The novel antiplatelet agents prasugrel and ticagrelor, seem to overcome genetic restrictions but in expense of increased bleeding rates. Achieving a balance between adequate platelet inhibition and bleeding complications is challenging. CONCLUSION: Genetic screening may provide valuable guidance towards an efficient antiplatelet treatment. However, the lack of randomized controls trials testing the effect of a genotype-guided therapy, forbids the implementation of genetic testing into clinical practice.

Effects of CYP2C19 Polymorphism on Endothelial Function, Arterial Stiffness and Inflammation in Coronary Artery Disease Patients Under Clopidogrel Treatment.

BACKGROUND: Clopidogrel's ability to inhibit platelet function determined its clinical usefulness. The role of CYP2C19*2 genotype on antiplatelet treatment is recently under question. Arterial wall properties and inflammation are key players in atherosclerosis development. Hence, we evaluated the impact of CYP2C19*2 genetic polymorphism on endothelial function, arterial stiffness and inflammation in coronary artery disease (CAD) patients receiving clopidogrel treatment. METHODS AND RESULTS: In this study we enrolled 408 consecutive patients with stable CAD under dual antiplatelet therapy (clopidogrel 75mg/day, aspirin 100mg/day), 30 days after percutaneous coronary intervention. Measurement of flow-mediated dilation (FMD) of the brachial artery was used to evaluate endothelial function. Carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) was measured to estimate arterial stiffness. Real time polymerase chain reaction was used for the genotyping of CYP2C19*2. Levels of tumor necrosis factor alpha (TNF-a) and interleukin 6 (IL-6) were measured with ELISA. We found no difference in basic clinical and demographic characteristics nor in FMD, PWV, AIx and inflammatory status (p=NS for all) between CYP2C19 homozygotes for the wild type; carriers of reduced function allele and homozygotes for the reduced function allele. CONCLUSION: CYP2C19*2 loss of action polymorphism causes no impact on vascular function and inflammatory status in stable CAD patients receiving clopidogrel treatment.

Clopidogrel response variability is associated with endothelial dysfunction in coronary artery disease patients receiving dual antiplatelet therapy.

OBJECTIVES: Dual antiplatelet therapy with aspirin and a platelet P2Y12 ADP receptor antagonist is the cornerstone of treatment following percutaneous coronary intervention (PCI). Several clinical and genetic factors can cause suboptimal clopidogrel response. We examined the impact of endothelial dysfunction on clopidogrel response variability in subjects with stable coronary artery disease (CAD) after PCI. METHODS: We consecutively enrolled 198 patients with stable CAD one month after successful PCI. All patients were receiving dual antiplatelet therapy (clopidogrel 75 mg and aspirin 100 mg/day). Platelet reactivity was measured by VerifyNow P2Y12 assay (Accumetrics, San Diego, CA). VerifyNow reports its results in P2Y12 reaction units (PRU) and the diagnostic cut-off value is 230. Endothelial function was evaluated by flow mediated dilation (FMD). RESULTS: Patients with high on treatment platelet reactivity (32% of the study population), compared to subjects with low on treatment platelet reactivity, presented decreased FMD values (4.35 ± 2.22% vs. 5.74 ± 3.29%, p = 0.01). Moreover, an inverse association between endothelial function measurement and platelet reactivity (r = -0.24, p = 0.001) was found. Importantly, multivariate analysis after adjustment for age, gender and confounders revealed by the univariate analysis (left ventricle ejection fraction, body mass index, diabetes, dyslipidemia, coronary lesion number) showed that for every decrease in FMD by 1% there is an anticipated increased in the odds of patients to have HPR by 1.66 (95% CI 1.03-2.57, p = 0.037). CONCLUSIONS: Endothelial dysfunction is associated with clopidogrel response variability in patients after PCI receiving dual antiplatelet therapy. These findings shed some light on the mechanisms affecting individual platelet response to antiplatelet therapy and may explain the non-straight forward association between clopidogrel dose, platelet inhibition and cardiovascular outcome.

Asymmetric Dimethylarginine: Clinical Significance and Novel Therapeutic Approaches.

Asymmetric dimethylarginine (ADMA) is a competitive endogenous inhibitor of nitric oxide synthase with a key role in the pathophysiology of endothelial dysfunction, in the progression of atherosclerosis and in cardiovascular diseases. Statins, renin-angiotensin-aldosterone system inhibitors, blood glucose lowering agents, insulin sensitizers, beta-blockers, estrogen replacement therapy, antioxidants, complex B vitamins, L-arginine and acetylsalicylic acid have been evaluated for their ability to reduce ADMA levels or inhibit its actions. Despite the major beneficial effects of these agents in cardiovascular disease, research has shown that their favorable actions are only partially mediated by reducing ADMA levels or by bypassing its effect in nitric oxide synthesis. Novel therapeutic approaches targeting selectively ADMA are encouraging, but have only been tested in vitro or in animal studies and further research is needed in order to conclude on how therapeutic strategies modulating ADMA actions can affect atherosclerosis progression and cardiovascular diseases.

Vascular function and ocular involvement in sarcoidosis.

Ocular involvement occurs in sarcoidosis (Sar) patients mainly in the form of uveitis. This study was designed to determine if uveitis in Sar patients is associated with vascular impairment. We enrolled 82 Sar patients and 77, age and sex matched, control subjects (Cl). Sar patients were divided into those with ocular sarcoidosis (OS) and those without ocular sarcoidosis (WOS). Endothelial function was evaluated by flow-mediated dilation (FMD). Pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections. Although there was no significant difference in sex, age and mean arterial pressure, patients with OS compared to WOS patients and Cl subjects had impaired FMD (p<0.001), increased AIx (p=0.02) and increased PWV (p=0.001). Interestingly, impaired FMD in Sar patients was independently, from possible covariates (age, sex, smoking habits, arterial hypertension, dyslipidemia), associated with increased odds of ocular involvement (odds ratio=1.69, p=0.001). More precisely ROC curve analysis revealed that FMD had a significant diagnostic ability for the detection of OS (AUC=0.77, p<0.001) with a sensitivity of 79% and a specificity of 68% for an FMD value below 6.00%. To conclude in the present study we have shown that ocular involvement in Sar patients is associated with impaired endothelial function and increased arterial stiffness. These results strengthen the vascular theory which considers uveitis a consequence of vascular dysfunction in Sar patients and reveals a possible clinical importance of the use of endothelial function tests.

Novel Inflammatory Biomarkers in Cardiovascular Therapeutics.

Inflammation has been established as an important determinant of cardiovascular disease progression. Currently, clinical examination, laboratory and imaging tests are invaluable for the diagnosis, prognosis and disease monitoring. Novel inflammatory biomarkers are also used to better restratify patients in risk groups but their potential to guide treatment decisions and management of patients has not been extensively evaluated. Therefore, in this review article we present the most recent data concerning the use of inflammatory biomarkers in cardiovascular therapeutics.