Development Of Future Cardiovascular Events Research Articles

Effects of Different Kinds of Physical Activity on Vascular Function.

Regular exercise is one of the main non-pharmacological measures suggested by several guidelines to prevent and treat the development of hypertension and cardiovascular disease through its impact on the vascular system. Routine aerobic training exerts its beneficial effects by means of several mechanisms: decreasing the heart rate and arterial pressure as well as reducing the activation of the sympathetic system and inflammation process without ignoring the important role that it plays in the metabolic profile. Through all these actions, physical training counteracts the arterial stiffening and aging that underlie the development of future cardiovascular events. While the role of aerobic training is undoubted, the effects of resistance training or combined-training exercise on arterial distensibility are still questioned. Moreover, whether different levels of physical activity have a different impact on normotensive and hypertensive subjects is still debated.

Inflammatory mediators and their special roles in diverse clinical circumstance

The involvement of inflammation is described in all stages of atherosclerosis as well as in dyslipidemias, particularly in lipoproteins (especially oxidized LDL), coronary syndromes, hypertension, diabetes, infections, obesity, and also in the use of sexual replacement hormones. From the first steps of leukocyte recruitment in the nascent atheromatic lesion to the development of atheroma plaque, culminating in its rupture and thrombosis in the acute coronary event, we found a constant release of inflammatory mediators, soluble in plasma, from macrophages, T lymphocytes, endothelial cells and smooth muscle vessels of the vessels, hepatocytes, and adipocytes. The greatest evidence relating inflammation to the future development of cardiovascular events has been verified in large-scale population studies. High concentrations of inflammatory markers such as TNF-α, IL-6, ICAM-1, P-selectin, E-selectin, C Reactive Protein, fibrinogen, and amyloid serum A, in apparently healthy individuals, have shown predictive value for future vascular events. Considering the multifactorial etiology of coronary artery disease and its inflammatory nature, it was possible to find an association between the presence of risk factors and the increase in the concentration of biomarkers of inflammation. TNF-α is a multifunctional cytokine derived from smooth endothelial and muscle cells, as well as macrophages present in the coronary atheroma. It is involved in a number of cardiovascular processes, being increased in congestive heart failure.

Endothelial Dysfunction in Psoriasis: An Updated Review.

Although psoriasis is predominantly a chronic inflammatory skin disorder, epidemiological data provide a solid link between psoriasis, especially in its more severe forms, and increased risk for cardiovascular morbidity and mortality. Apart from the increased prevalence of traditional cardiovascular risk factors, chronic inflammation appears to act synergistically with the underlying process of endothelial dysfunction toward the development of accelerated atherosclerosis, subclinical vascular injury and subsequently, clinically evident cardiovascular manifestations. Endothelial dysfunction is regarded as an early precursor of atherosclerosis with a predictive value for the development of future cardiovascular events. A thorough understanding of the mechanisms of endothelial dysfunction in psoriasis might pave the path for the development of more accurate cardiovascular risk prediction tools and possible therapeutic targets aiming to alleviate the increased cardiovascular burden associated with the disease. The present review summarizes the available evidence about the role of chronic inflammation and other important pathophysiological mechanisms involved in the development of endothelial dysfunction in psoriasis. An overview of studies implementing the most widely applied circulating and vascular biomarkers of endothelial dysfunction in psoriasis patients will be provided, and the impact of systemic psoriasis treatments on endothelial dysfunction and patients’ cardiovascular risk will be discussed.

Incremental value of the measures of arterial stiffness in cardiovascular risk assessment.

Predicting the occurrence of organ damage and future cardiovascular events is critical to improving patient prognosis through early personalized treatment. Although many tools have been developed and used for individuals' cardiovascular risk, they have limitations and unmet needs for improved risk stratification. For this purpose, arterial stiffness information can be practical. Arterial walls stiffen with age or prolonged exposure to various noxious stimuli such as high blood pressure, hyperglycemia, inflammation and oxidative stress. Differently from several methods of measuring arterial stiffness, pulse wave velocity (PWV) is most widely used for its non-invasive and easy measurement. It is well authorized that information on arterial stiffness is associated with the development of future cardiovascular events, independent from traditional cardiovascular risk factors, in various patient groups with specific diseases along with the general population. Moreover, when this information of arterial stiffness is associated with other risk stratification tools, it is possible to predict individuals' cardiovascular risk easier. Herein, we will review the incremental value of the measurement of arterial stiffness in cardiovascular risk assessment when combined with other risk factors such as traditional risk factors, biomarkers, other vascular testing and non-invasive cardiac imaging.

Uticaj metaboličkih parametara na veličinu i subklasu LDL i HDL kod adolescenata sa dijabetesom tip 1

Alterations in the serum of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) size and subclass contribute to the atherogenesis in coronary artery disease in diabetic patients. The purpose of this study is to evaluate the effect of metabolic parameters on LDL and HDL size and subclasses in adolescents with type 1 diabetes. The cross-sectional study included 43 adolescents (23 females, 20 males) with type 1 diabetes of mean age 15.09±1.94 years, with mean disease duration of 5.86 ± 3.08 years. LDL and HDL particles were separated by polyacrylamide gradient gel electrophoresis, while serum lipid parameters were determined by routine laboratory methods. Patients with inadequate metabolic control (HbA1c ≥ 7.5%) had a higher mean value of triglycerides (TG) (p = 0.041), higher proportions of small, dense LDL particles (p = 0.045), higher proportions of LDL IIA subclasses (p=0.03) and smaller LDL diameter (p = 0.02) and HDL diameter (p = 0.04) than patients with optimal metabolic control (HbA1c < 7.5%). Higher HbA1c and higher TG levels were statistically significantly related to small, dense LDL (r=0.341, p=0.025; r= 0.394, p= 0.009) and HDL particles (r=0.684, p=0.000; r=0.421, p=0.005). Predictors of small, dense LDL and HDL particles, which contribute to atherogenesis, were high HbA1c (HR = 1.52, 95% CI: 0.97-2.40; HR 3.87, 95% CI: 2.11-7.10) and elevated TG (HR= 1.10, 95% CI: 1.00-1.20; HR 1.85, 95% CI: 1.07-3.21). Diabetic adolescents require particular attention in order to minimize factors such as high HbA1c and elevated TGs in the development of future cardiovascular events.

Anthracycline-Induced Cardiotoxicity: The Role of Endothelial Dysfunction

Cardiovascular disease remains the leading cause of mortality accounting up to 40% of all deaths, but, currently, cancer is prominent cause of death globally. Anthracyclines are the cornerstone of chemotherapy in women with breast cancer. However, its clinical use is limited by their cardiotoxic effects that can trigger heart failure development. Vascular toxicity of chemotherapy may be linked with endothelial dysfunction because anthracycline damage of endothelial cells can lead to the development and progression of cardiomyopathy by decreasing the release and activity of endothelial factors and, ultimately, endothelial cell death. These processes suppress anti-inflammatory and vascular reparative functions and initiate the development of future cardiovascular events. Recent studies have shown that chemotherapy may induce toxicity in the vascular endothelium and is accompanied by systemic endothelial dysfunction in patients with diagnosed cardiovascular diseases. Because the initial endothelial cell insult is likely asymptomatic, there is often a long delay between the termination of doxorubicin therapy and the onset of vascular disorders. In this case, genetic susceptibility factor will help to identify susceptible patients in the future. The objectives of this study were to evaluate prognostic role of molecular (endothelin-1) and genetic factors (gene polymorphisms of endothelial nitric oxide (NO) synthase (NOS3, rs1799983), endothelin-1 receptor type A (EDNRA, C+70G, rs5335) and NADPH oxidase (C242T, rs4673) in development of endothelial dysfunction and anthracycline-induced cardiotoxicity in women without cardiovascular diseases.

MO056MODIFICATION OF P16, P21 AND NRF2 EXPRESSION IN A MODEL OF UREMIC VASCULAR CALCIFICATION

Abstract Background and Aims Vascular calcification (VC) is a consequence of ageing that confers development of future cardiovascular events. Accumulation of senescent cells can lead to structural and functional abnormalities in vessel wall towards increased stiffness, reduced compliance and impaired contractile and dilatory capacity. Thus, accumulation of senescent cells in the arterial wall could also contribute to the pathophysiology of VC. To test this hypothesis, the presence of cellular markers of senescence, p16, p21 and NRF2, was assessed in aorta from rat model of VC associated with chronic kidney disease (CKD). Method Six-week-old Sprague-Dawley rats underwent 5/6th subtotal nephrectomy (SNx, n=6) or no surgery (Control, n=1). After 8 weeks of renal failure, the regular chow was supplemented with high phosphate (1.2%) and vitamin D (1 µg/day, 5 days per week) for 1 or 4 weeks to initiate vascular calcification (SNx-VC group). At the end of the protocol (Figure 1), blood pressure was measured, and thoracic aorta was taken for determination of calcification by Von Kossa staining, and protein and gene expressions of p16, p21, and NRF2 by immunostaining and qPCR, respectively. Results After 4 weeks of dietary intervention, SNx rats showed an increase in pulse pressure (88±15mmHg vs 35 mmHg for the control). Marked VC was also observed in these animals, 17% of calcified area vs <1 % in the control rat. Calcification was focal giving strong and no calcified areas on the same aorta. Expressions of p16, p21and NRF2 proteins were enhanced at the site of calcification in the SNx-VC 4-week (4W) group whereas it was unchanged in aortic media without calcification compared to the control rat (Figure 2). In SNx-VC 1-week (1W) rats, no change in pulse pressure or vascular calcification was observed without obvious changes for staining patterns of selected markers. Using qPCR we found p16 gene expression to be higher in the most calcified aortas (4W) (fold-change = 4.32 vs 1W) and p21 gene expression to be slightly increased (fold-change = 0.53 vs 1W). NRF2 gene expression was enhanced in 1W group compared to control, but decreased in the most calcified samples (4W). Conclusion This pilot study suggests that uraemia-induced cellular senescence accompanies VCs, as suggested by the modified expression of p16 or NRF2 genes. Our observations deserve exploration in larger studies using additional senescence markers for validation. If so, cellular senescence kinetics will be evaluated in order to test whether senolytics compounds could be a therapeutic option to arrest VC in CKD.

Understanding and predicting fatigue, cardiovascular (CV) decline & events after breast cancer treatment (UPBEAT): A prospective multi-center wake forest NCORP research-base study.

TPS602 Background: Modern treatment for breast cancer (BC) has led to improved survival; however, this improvement can be offset by an increase in cancer therapy-related morbidity and mortality. Over one-third of early stage BC patients treated with cancer therapy experience CV injury, left ventricular (LV) dysfunction, exercise intolerance, or fatigue. CV disease is a leading cause of mortality in BC survivors. There is limited information on the time course and long-term CV health of BC survivors. UPBEAT, a multicenter study, will prospectively evaluate CV risk factors and outcomes in early stage BC patients, treated with modern anticancer therapies. This will facilitate evaluation of primary CV prevention strategies in this patient population. Methods: This is a prospective cohort study of 840 patients with early stage (I-III) BC treated with chemotherapy +/- radiation and 160 controls. Baseline and serial longitudinal measures will examine the influence of cancer treatment on CV function, exercise capacity and fatigue, and the future development of CV events. The comprehensive assessment includes: ascertainment of cardiac biomarkers, CV risk factors, comorbidities, functional status (e.g., disability measures, expanded short physical performance battery), neurocognitive tests, behavioral risk factors, socio-demographics, and quality of life at baseline, 3-, 12-, and 24-mos. Outcomes measured at the same time points include a deep phenotyping of CV dysfunction (via cardiac MRI assessing LV end diastolic volume, LV end systolic volume, LV ejection fraction, myocardial strain, strain rate, left atrial volumes and mass, and aortic stiffness), exercise intolerance (submaximal as 6-minute walk test and maximal as VO2 peak via cardiopulmonary exercise test), and fatigue (via FACT-F). Eligibility criteria: age > 18 years; ECOG 0-2, able to walk without symptoms; receiving chemotherapy +/- HER2 targeted agent(s). To date, 244 participants are enrolled through 12 NCORP or ECOG-ACRIN sites. An additional 7 sites are onboarding and will be enrolling later in the year. Participants will be followed for 9 years with active surveillance of CV events (i.e., heart failure, myocardial infarction, stroke, all-cause and CV death). EA NCORP Grant: 2 UG1 CA189828 06; Research Base Grant: 2UG1 CA189824; R01: 1R01CA199167. Clinical trial information: NCT02791581 .

High-sensitivity C-reactive Protein as a Marker of Future Cardiovascular Events in Chronic Kidney Disease Stage-5 Patients

Introduction: Chronic Kidney Disease (CKD) has been recognised as a worldwide health threat and understanding its complex patho-physiological mechanisms could go a long way in taking care of patients with CKD. One of the most important causes for mortality in End Stage Renal Disease (ESRD) patients is Cardiovascular Disease (CVD). ESRD is a low grade chronic inflammatory state, suspected to promote atherosclerosis. Aim: To determine, if there is any association between elevated High-sensitivity C-Reactive Protein (hs-CRP) and development of future cardiovascular events in stage-5 CKD patients. Materials and Methods: Forty-five CKD stage-5 patients were included in the study, after ruling out patients with established CVD. According to categorisation proposed by the American Heart Association for the cut-off value of hs-CRP-value (3 mg/L), patients were divided into two groups. Those who had hs-CRP more than 3 mg/L were considered to have ‘elevated hs-CRP’ and those who had a value 3 mg/L and below were considered to have ‘normal hs-CRP’ levels. These patients were followed-up monthly, for a period of one year to record any occurrence of cardiovascular events (coronary events/cerebrovascular accidents/peripheral occlusive vascular disease). Statistical Package for the Social Sciences (SPSS) 16.0 was used for analysis. Chi-square test and Mann-Whitney U-test were used for statistical comparison between the groups and a p-value of 0.05 or less was considered to be statistically significant. Receiver Operating Characteristic (ROC) curve was also plotted to determine the cut-off value for hs-CRP based on the occurrence of any cardiovascular event. Results: Baseline hs-CRP level was more than 3 mg/L in 42% of patients. Among those who had elevated hs-CRP, 78.9% of patients developed cardiovascular events during the follow-up period. This signifies a strong association between elevated hs-CRP and CVD in ESRD patients. The hs-CRP cut-off point of 3 mg/L was obtained from ROC curve. Conclusion: There was a significant association between elevated hs-CRP and development of cardiovascular events in ESRD patients. Hence, hs-CRP can be used as a marker of future cardiovascular events in CKD stage-5 patients.

Understanding and predicting fatigue, cardiovascular (CV) decline, and events after breast cancer treatment (UPBEAT): A prospective cardio-oncology study.

TPS11634 Background: Modern treatment for breast cancer (BC) has led to improved survival; however, this improvement can be offset by an increase in cancer therapy-related morbidity and mortality. Over one-third of early stage BC patients treated with cancer therapy experience CV injury, left ventricular (LV) dysfunction, exercise intolerance, or fatigue. CV disease is a leading cause of mortality in BC survivors. There is limited information on the time course and long-term CV health of BC survivors. UPBEAT, a multicenter study, will prospectively evaluate CV risk factors and outcomes in early stage BC patients,treated with modern cancer therapies. This will facilitate evaluation of primary CV prevention strategies in this patient population. Methods: This is a prospective cohort study of 840 patients with early stage (I-III) BC treated with chemotherapy +/- radiation and 160 controls. Baseline and serial longitudinal measures will examine the influence of cancer treatment on CV function, exercise capacity and fatigue, and future development of CV events. The comprehensive assessment of factors includes ascertainment of cardiac biomarkers, CV risk factors, comorbidities, functional status (e.g., disability measures, Expanded SPPB), neurocognitive tests, behavioral risk factors, socio-demographics, and quality of life at baseline, 3-, 12-, and 24-mos. Outcomes measured at the same time points, include a deep phenotyping of CV dysfunction (via cardiac MRI assessing LV end diastolic volume, LV end systolic volume, LV ejection fraction, myocardial strain, strain rate, left atrial volumes and mass, and aortic stiffness), exercise intolerance (submaximal as 6-minute walk test and maximal as VO2peak via cardiopulmonary exercise test), fatigue (via FACT-F). Eligibility criteria are: age >18 years; ECOG 0-2, able to walk without symptoms; and for BC patients, treatment with chemotherapy. 143 participants are accrued and currently enrolling through ECOG and NCORP sites. Participants will be followed for 9 years with active surveillance of CV events, i.e., heart failure, myocardial infarction, stroke, all-cause and CV death. Clinical trial information: NCT02791581.

Circulating Stem/Progenitor Cells as Prognostic Biomarkers in Macro- and Microvascular Disease: A Narrative Review of Prospective Observational Studies.

Circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) are immature cells involved in vascular repair and related to many aspects of macro and microvascular disease. We aimed to review studies reporting the prognostic role of CPCs/EPCs measurement on development of cardiovascular disease and microangiopathy. We reviewed the English language literature for prospective observational studies reporting the future development of cardiovascular disease or microangiopathy in patients having a baseline determination of CPCs/EPCs. We retrieved 34 studied reporting on cardiovascular outcomes and 2 studies reporting on microvascular outcomes. Overall, a reduced baseline level of CPCs/EPCs was associated with a significant increased risk of cardiovascular events, all-cause death, and onset/progression of microangiopathy. The most predictive phenotypes were CD34+ and CD34+CD133+. The main limitation was related to the high heterogeneity among studies in terms of patient characteristics and cell phenotypes. The present review shows that a reduced level of circulating progenitor cells is a risk factor for the development of future cardiovascular events and death. In addition, low CPCs/EPCs levels predict the onset or worsening of microalbuminuria and retinopathy in diabetic patients.

PS 02-41 HYPERPULSATILE PRESSURE, SYSTEMIC INFLAMMATION AND CARDIAC STRESS ARE ASSOCIATED WITH CARDIAC WALL REMODELLING IN AN AFRICAN MALE COHORT

Objective: Inflammation may contribute to an increase in cardiac wall stress through multiple pathways related to cardiac remodeling. Cardiac remodeling is a compensatory mechanism characterised by myocyte hypertrophy, myocyte death and modifications of the extra-cellular matrix. We aimed to explore associations of inflammation and myocardial injury with cardiac remodeling in a bi-ethnic sex cohort of South Africa. Design and Method: We included 165 men (76 African and 89 Caucasian) and 174 women (80 African and 94 Caucasian) participants between 20 and 65 years of age. Inflammatory markers that were employed were C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-alpha (TNF-α), while troponin T (Trop T) and the N-terminal of pro B-type natriuretic peptide (NT-proBNP) were employed as cardiac markers. Frequency of ischemic events (ST segment depression) and left ventricular strain (left ventricular hypertrophy: LVH) were monitored by recording ambulatory 24-h blood pressure (BP), -ECG and 12 lead standard ECG. Results: Hypertension diagnosed with ambulatory monitoring was more evident in Africans (53.85% vs. 24.59%; p < 0.001) as was the number of ischemic events (6 vs 3; p = 0.006) irrespective of sex. Inflammatory markers (CRP, IL-6 and TNF-α) were significantly higher in Africans, as were Trop T concentrations and degree of LVH (p < 0.05). BP was associated (p < 0.05) with Trop T in all men. In African men, associations were evident between cardiac stress (NT-proBNP), TNF alpha (p < 0.001), Trop T (p < 0.001) and pulse pressure (p = 0.048), adjusted R2 = 0.45. Conclusions: A risk profile of overload to the heart will increase the susceptibility for cardiac wall remodeling, characterised by hyper- pulsatile pressure, low-grade systemic inflammation and ventricular stress, which may lead to the development of future cardiovascular events in African men.

Hyperpulsatile pressure, systemic inflammation and cardiac stress are associated with cardiac wall remodeling in an African male cohort: the SABPA study.

Inflammation may contribute to an increase in cardiac wall stress through pathways related to cardiac remodeling. Cardiac remodeling is characterized by myocyte hypertrophy, myocyte death and modifications of the extracellular matrix. We sought to explore associations among cardiac remodeling, inflammation and myocardial cell injury in a bi-ethnic cohort of South African men and women. We included 165 men (76 African and 89 Caucasian) and 174 women (80 African and 94 Caucasian) between 20 and 65 years of age. Inflammatory markers used were C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-alpha (TNF-α), whereas troponin T (Trop T) and the N-terminal of pro B-type natriuretic peptide (NT-proBNP) were used as cardiac markers. The frequency of ischemic events (ST segment depression) and left ventricular strain (left ventricular hypertrophy: LVH) were monitored by a 24-h recording of ambulatory blood pressure (BP), ECG and 12-lead standard ECG. Hypertension diagnosed with ambulatory monitoring was more frequent in Africans (53.85 vs. 24.59%; P<0.001), as was the number of ischemic events (6±15 (1; 5) vs. 3±6 (0; 3)). Inflammatory markers (CRP, IL-6 and TNF-α) and the degree of LVH were all significantly higher in Africans (P<0.05). BP was associated (P<0.05) with Trop T in men across ethnic groups. In African men, cardiac stress (NT-proBNP) was associated with TNF-alpha (P<0.001), Trop T (P<0.001) and pulse pressure (P=0.048; adjusted R(2)=0.45). The susceptibility for cardiac wall remodeling appears to increase with hyperpulsatile pressure, low-grade systemic inflammation and ventricular stress, and may lead to the development of future cardiovascular events in African men.

High sensitivity C-reactive protein in metabolic syndrome

Background: Presence of metabolic syndrome in an individual substantially increases his risk of developing cardiovascular disease and type 2 diabetes mellitus. Occurrence of both obesity and type 2 DM have reached epidemic proportions in India. Metabolic syndrome is considered to be a proinflamatory state associated with low grade systemic inflammation. C- reactive protein is a robust biomarker of this chronic systemic inflammation. Higher values of high sensitivity C- reactive protein (hs-CRP) are associated with metabolic syndrome and its components and provides additional prognostic information on future development of cardiovascular events in them. Methods: 50 patients aged 18 years and above with metabolic syndrome, and 50 age and sex matched controls attending OPD or admitted to medicine department wards of Bangalore Medical College were enrolled for this cross sectional study. The new IDF criteria were used for the diagnosis of metabolic syndrome. A fasting blood sample was drawn for estimation of hs-CRP, blood glucose and lipid profile. Waist circumference, height and weight were measured at the same time. The results were tabulated and analysed. Results: There was a statistically significant difference in values of various demographic parameters like BMI, waist circumference, BP and biochemical parameters like blood sugar, lipid profile between cases and controls. Patients with metabolic syndrome had higher mean value of hs-CRP (8.3±1.04 Vs 1.6±0.79mg/l) with a p value <0.001. Conclusions: Patients with metabolic syndrome had significantly higher levels of hs-CRP when compared to controls and hs-CRP levels increased linearly with increasing number of metabolic syndrome components. Hence hs-CRP can probably be used as a surrogate marker of chronic inflammation in patients with metabolic syndrome.

Do incretins improve endothelial function?

An impaired endothelial function has been recognized in the early stage of atherosclerosis, and is a major factor affecting the future development of cardiovascular events. Type 2 diabetes mellitus (T2DM) is widely prevalent, and is one of the most important risk factors for cardiovascular disease. T2DM is associated with increases in both morbidity and mortality, particularly from cardiovascular disease.New therapies based on the incretin hormone and its actions are now becoming widely used, and appear to offer advantages over conventional therapies by keeping the body weight steady and limiting hypoglycemia, while also achieving attractive glycemic control. However, there is little data available about the effects of incretins on the cardiovascular system.This review will focus on the effects of incretin therapies, including glucagon-like peptide-1 (GLP-1) analogs and dipeptidyl peptidase (DPP)-4 inhibitors, on the endothelial function, and will discuss the potential mechanisms underlying these effects.

Metabolic syndrome and insulin resistance comorbidity in systemic lupus erythematosus

The aim of the present study was to assess the effect of metabolic syndrome (MetS) and insulin resistance comorbidity on the carotid intima-media thickness (IMT) in systemic lupus erythematosus (SLE) patients and their relationship to clinical manifestations, disease activity, and damage. The study included 92 SLE patients (mean age 30.18 ± 8.27years) and 30 matched controls. Disease activity and damage were assessed by the SLEDAI and SLICC indices, respectively. The Health Assessment Questionnaire II (HAQII) and Quality of Life (QoL) index were evaluated in the patients. Levels of insulin, glucose, and creatinine and the lipid profile were measured in patients and controls. Insulin sensitivity was estimated using the homeostatic model assessment index (HOMA-B) for beta cell function and (HOMA-IR) for peripheral tissue insulin resistance. The carotid IMT was measured by ultrasonography. The SLE patients had high HOMA-IR and HOMA-B. The IMT was significantly increased (0.82± 0.29mm) compared to the controls (0.45± 0.2mm).The HOMA-IR, SLEDAI, SLICC, HAQII, and IMT were significantly higher and the QoL lower in those with MetS (n = 34) compared to those without (n = 58), while the HOMAB was comparable. There was a significant correlation between the IMT and the SLEDAI, SLICC, and WHR. Insulin sensitivity and IMT are altered in SLE patients, especially those with MetS comorbidity with an associated increase in disease activity and damage. Effective management of MetS would help control SLE activity, damage, and the future development of cardiovascular events especially in the absence of symptoms of cardiovascular disease.

Microalbuminuria breakthrough under chronic renin–angiotensin–aldosterone system suppression

Microalbuminuria has been shown to be a potent predictor for future development of cardiovascular and renal events that can be prevented by the use of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs). Both classes of drugs are now-a-days widely used in the treatment of arterial hypertension since the very early stages of the cardiorenal continuum when only cardiovascular risk factors are detected. We describe here the development of de-novo microalbuminuria in patients chronically treated with either an ACEi or an ARB at adequate doses. We reviewed the evolution of 1433 patients (mean age 60.5 ± 12.4 years, 50.3% men, 6.6% having type 2 diabetes), arriving in our hospital-based Hypertension Unit previously treated for a least 2 years either with an ACEi or an ARB, at adequate doses, alone or in combination with other antihypertensive drugs. A total of 184 (16.1%) patients developed new-onset microalbuminuria, whereas macroalbuminuria was detected in 11 (1.0%) patients at the end of follow-up. Albuminuria appeared at any level of blood pressure (BP) from below 130/80 mmHg, albeit the highest percentage was seen when SBP was above 160 mmHg. De-novo microalbuminuria was more frequent in those patients presenting with established cardiovascular disease and predicts the future development of cardiovascular events but was not accompanied by a significant worsening of renal function. These data indicate that a reappraisal of renin-angiotensin-aldosterone system (RAAS) suppression is required when microalbuminuria appears in patients under chronic RAAS suppression.

Noninvasive Measurement of Plasma Triglycerides and Free Fatty Acids from Exhaled Breath

Although altered metabolism has long been known to affect human breath, generating clinically usable metabolic tests from exhaled compounds has proven challenging. If developed, a breath-based lipid test would greatly simplify management of diabetes and serious pathological conditions (e.g., obesity, familial hyperlipidemia, and coronary artery disease), in which systemic lipid levels are a critical risk factor for onset and development of future cardiovascular events. We, therefore, induced controlled fluctuations of plasma lipids (insulin-induced lipid suppression or intravenous infusion of Intralipid) during 4-h in vivo experiments on 23 healthy volunteers (12 males/11 females, 28.0 ± 0.3 years) to find correlations between exhaled volatile organic compounds and plasma lipids. In each subject, plasma triglycerides (TG) and free fatty acids (FFA) concentrations were both directly measured and calculated via individualized prediction equations based on the multiple linear regression analysis of a cluster of 4 gases. In the lipid infusion protocol, we also generated common prediction equations using a maximum of 10 gases. This analysis yielded strong correlations between measured and predicted values during both lipid suppression (r = 0.97 for TG; r = 0.90 for FFA) and lipid infusion (r = 0.97 for TG; r = 0.94 for FFA) studies. In our most accurate common prediction model, measured and predicted TG and FFA values also displayed very strong statistical agreement (r = 0.86 and r = 0.81, respectively). Our results demonstrate the feasibility of measuring plasma lipids through breath analysis. Optimization of this technology may ultimately lead to the development of portable breath analyzers for plasma lipids, replacing blood-based bioassays.

Assessment of coronary endothelial function using PET

Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. Several coronary risk factors adversely affect endothelial function. Therefore, a finding of endothelial dysfunction may guide interventions for preventing the development of future cardiovascular events. The non-invasive aspects and coronary specificity of measurements of myocardial blood flow (MBF) using positron emission tomography (PET) with sympathetic stress make it widely applicable for the evaluation of endothelial function. PET MBF measurements with sympathetic stress have been applied to a variety of subjects with coronary risk factors and have been shown to have value for risk assessment in these subjects. Endothelial measurement using PET remains an ideal research tool for the study of the pathophysiology of several cardiac diseases. PET is also well suited for the acute and longitudinal evaluation of treatment. Thus, the continued development of this approach for the evaluation of new treatment effects should be expected.

Six-step management of hypertension in patients with rheumatoid arthritis

Hypertension is one of the major risk factors for cardiovascular disease. Its prevalence in patients with rheumatoid arthritis is equal to, if not higher than, that in the general population, as is the attributable risk to the development of future cardiovascular events. Despite its serious complications, control of hypertension is far from adequate in the general population and even more so in rheumatoid arthritis patients. The constellation of inflammation, physical inactivity, polypharmacy and difficulties implementing primary prevention render the management of hypertension in rheumatoid arthritis patients a very challenging task. In this article we attempt to unravel the complexity of managing hypertension in rheumatoid arthritis patients and make practical recommendations that may be useful in clinical practice.