Subclinical Damage Research Articles

Prevalence, Incidence, and Contributors of Subclinical Atheromatosis, Arteriosclerosis, and Arterial Hypertrophy in HIV-Infected Individuals: A Single-Center, 3-Year Prospective Study.

Cardiovascular disease (CVD) is an important comorbidity for people living with HIV infection (PLWH) in the combined antiretroviral therapy era. We prospectively examined the presence of subclinical arterial disease in 138 consecutive CVD-free, HIV-infected individuals compared to 664 HIV-negative individuals. We studied 10 arterial sites in 4 beds using 5 distinct biomarkers of subclinical atheromatosis, arteriosclerosis, and hypertrophy and evaluated the association of subclinical arterial damage with CVD-related and HIV-related factors at baseline and at 3-year follow-up. Atheromatosis, arteriosclerosis, and arterial hypertrophy were present in 36.1%, 59.7%, and 34.3% of HIV-infected individuals, respectively, at baseline. HIV infection was independently associated with carotid atheromatosis and hypertrophy. The presence of carotid atheromatosis was independently associated with age, years of smoking, and exposure to nonnucleoside reverse transcriptase inhibitors (NNRTIs). The annual incidence of atheromatosis, arteriosclerosis, and arterial hypertrophy was 5.5, 18.6, and 12.5 cases/100 patients, respectively. Carotid atheromatosis progression was significantly associated with NNRTI exposure. People living with HIV infection exhibited high prevalence and incidence of subclinical arterial damage and site-specific predilection for the carotids. These investigations may help optimize HIV-specific CVD prediction models. The NNRTIs may contribute to atheromatosis, emphasizing the need to consider the atherogenic potential of antiretroviral drugs in management strategies.

Absence of effect of the antiretrovirals Duovir and Viraday on mitochondrial bioenergetics.

Most toxicity associated with antiretroviral drugs is thought to result from disruption of mitochondrial function. Unfortunately, there are no validated laboratory markers for clinically assessing the onset of mitochondrial toxicity associated with antiretroviral therapy. In a previous study on mitochondrial hepatocytes, the protease inhibitor lopimune was shown to induce mitochondrial toxicity by increasing reactive oxygen species (ROS) production and decreasing respiratory control ratio (RCR) reflecting compromised mitochondrial efficiency in adenosine triphosphate production. Mitochondrial dysfunction and ROS production were directly correlated with the expression of uncoupling protein 2 (UCP2). In the current study we aim to determine the toxicity of nucleoside or nucleotide and nonnucleoside reverse-transcriptase inhibitors, Duovir and Viraday on liver mitochondria isolated from treated mice by monitoring UCP2 expression. Our results showed that both Duovir and Viraday had no effect on mitochondrial respiration states 2, 3, 4, and on RCR. In addition, ROS generation and UCP2 expression were not affected. In conclusion, our results indicate the difference in the mechanism of action of distinct classes of antiretroviral drugs on mitochondrial functions and may associate UCP2 expression with subclinical mitochondrial damage as marker of cellular oxidative stress.

The Expanded Risk Score in Rheumatoid Arthritis (ERS-RA): performance of a disease-specific calculator in comparison with the traditional prediction scores in the assessment of the 10-year risk of cardiovascular disease in patients with rheumatoid arthrit

To assess the performance of the Expanded Risk Score in Rheumatoid Arthritis (ERS-RA), a disease-specific cardiovascular disease (CVD) prediction score, in evaluating the 10-year risk, in comparison with other traditional algorithms in patients with rheumatoid arthritis (RA). Consecutive RA patients, aged 40-75 years, without established CVD, were included. We calculated the disease-specific ERS-RA and four traditional CVD prediction scores: the modified Systematic Coronary Risk Evaluation (mSCORE), the Framingham Risk Score using body mass index (FRS BMI), the calculator developed by the American College of Cardiology / American Heart Association in 2013 (ACC/AHA 2013) and the QRISK3. Subjects also underwent ultrasound assessment of the carotid arteries. The presence of a carotid intima-media thickness (CIMT) >0.90 mm or of carotid plaques identified the high-risk patients. Of the 84 patients evaluated, 33 (39.3%), 16 (19.0%), 24 (28.6%), 25 (29.8%) and 33 (39.3%) subjects were defined as having high CVD risk according to ACC/AHA 2013, mSCORE, FRS BMI, QRISK3 and ERS-RA, respectively. Compared with the ultrasound results, all the areas under the receiver operating characteristic curves (AUC-ROC) showed good discrimination properties (0.848 - FRS BMI, 0.816 - mSCORE, 0.828 - ACC/AHA 2013, 0.844 - QRISK3, 0.869 - ESR-RA). Comparison of the AUC-ROCs did not show that discriminative ability for detecting subclinical atherosclerotic damage was improved with ESR-RA. Using a surrogate marker of subclinical atherosclerotic organ damage as indicator of CVD burden, the newly ERS-RA risk score that incorporates specific aspects of RA performs as well as ACC/AHA 2013, mSCORE, FRS BMI and QRISK3 estimators.

Use of Speckle Tracking Echocardiography to Assess Left Ventricular Systolic Function in Patients with Surgically Repaired Tetralogy of Fallot: Global and Segmental Assessment.

Patients with repaired Tetralogy of Fallot (rToF) can have significant right and left ventricular dysfunction which can impact clinical outcome. Conventional echocardiographic evaluation using ejection fraction can be limited in detecting early stages of deteriorating left ventricular (LV) systolic function. Speckle-tracking echocardiography (STE) provides a promising emerging tool for early detection of LV systolic dysfunction. The aim of this cross-sectional study is to evaluate the left ventricular global and regional function using STE in rToF patients with preserved left ventricular ejection fraction to detect early signs of LV dysfunction. The study is a retrospective review of the medical records and transthoracic echocardiograms of rTOF patients who were seen in the pediatric cardiology clinic at our institution from August 2016 till May 2018. The rTOF group was compared with a matched healthy control group. Offline strain analysis of TTE studies was completed in each subject according to mode set by the American Society of Echocardiography. Twenty-two patients with rTOF and 22 age-matched controls (rTOF 18.7 ± 6years and control 14.6 ± 9.6 years, P value 0.19) were included during the study period. The rTOF group consisted of 12 males and 10 females, whereas the control group consisted of 15 males and 7 females. There was no significant difference in terms of LV ejection fraction using both 2-chamber as well as 4-chamber views. Global LV longitudinal strain was significantly lower in the rTOF group compared with the control group (rTOF - 15.92 ± 3.16 vs control - 22.79 ± 2.45, P value 0.00). All 17 segments showed significantly lower longitudinal strains in rTOF group compared with the control group. Global circumferential left ventricle strain was significantly lower in the rTOF patients compared with the control group (- 17.24 ± 5.86 vs - 22.74 ± 3.99, P value 0.001). 13 out of 16 segments had lower circumferential strains in the rTOF patients compared with controls. Asymptomatic surgically repaired TOF patients exhibited abnormal segmental and global left ventricle longitudinal and circumferential strains despite having normal left ventricle ejection fraction. Our findings suggest subclinical damage to the left ventricle systolic function post-surgical repair of TOF. 2-D speckle-tracking echocardiography may be used as a valuable method in the early recognition of left myocardial systolic function impairment in patients after TOF repair. The application of this method to guide clinical decision and management of rTOF patients such as earlier pulmonary valve replacement or risk stratification for sudden cardiac death needs further investigation.

Subclinical cardiovascular damage in patients with HCV cirrhosis before and after treatment with direct antiviral agents: a prospective study.

Cirrhosis is associated with morpho-functional cardiovascular alterations. To detect early features of cardiovascular damage in HCV-compensated cirrhotic patients using myocardial deformation indices and carotid arterial stiffness, and, further, to evaluate their short-term behaviour after HCV eradication with direct antiviral agents (DAAs). Thirty-nine consecutive patients with HCV cirrhosis, without previous cardiovascular events, were studied and matched for age, gender and cardiovascular risk factors to 39 controls without liver or cardiovascular disease. Patients and controls underwent a baseline echocardiographic evaluation including global longitudinal strain and ultrasound scan of carotid arteries. HCV-cirrhotics were reassessed by echocardiography and carotid ultrasound after obtaining sustained virological response (SVR) on DAAs. HCV-cirrhotics showed at baseline a significantly reduced global longitudinal strain compared to controls -18.1 (16.3-20.5) vs -21.2 (20.4-22.3), P<0.001. They also had a significantly higher pulse wave velocity 8.6 (7.7-9.1) m/s vs 6.6 (6.0-7.1) m/s, P=0.0001, and β-stiffness index 12.4 (11.1-13.5) vs 8.6 (8.0-9.2) P=0.0001. At multiple regression analysis, diabetes and HCV cirrhosis were independent predictors of global longitudinal strain. All HCV-cirrhotic patients had SVR on DAAs. Follow-up available in 32 of 39 (82%) at 9 (8-10) months showed a significant improvement of tricuspid annular plane systolic excursion (P=0.01) and lateral E' velocity compared to baseline (P=0.001). HCV-cirrhotics show a significant rate of subclinical cardiac and vascular abnormalities. At a time when their survival is less linked to progression of liver disease, due to viral eradication on DAAs, cardiovascular morbidity and mortality may take a significant role.

Childhood pulse pressure predicts subclinical vascular damage in adulthood: the Beijing Blood Pressure Cohort Study.

We aimed to investigate associations of childhood pulse pressure (PP) and change in PP status with adult subclinical vascular damage. Data were obtained from a population-based cohort of children aged 6-18 years started in 1987. The study constituted 1254 participants who were followed up in 2010-2011 (aged 28-42 years). Carotid arteriosclerosis and aortic stiffness were assessed by carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (PWV), respectively. Both childhood PP and mean arterial pressure (MAP) were independently associated with adult carotid IMT and PWV adjusted for sex, childhood age, follow-up duration, and other traditional cardiovascular risk factors. After further adjustment for adult values of PP and MAP, childhood PP was still associated with adult carotid IMT but not with PWV, whereas childhood MAP was associated with adult PWV but not with carotid IMT. In addition, compared with participants who had normal PP in both childhood and adulthood, participants who had high PP in adulthood, irrespective of their childhood PP status, had higher levels of carotid IMT and PWV (all P < 0.05). Participants who had high PP in childhood and normal PP in adulthood also had higher levels of adult carotid IMT but similar levels of PWV compared with participants who had consistently normal PP. Large PP in childhood plays an important role in the development of subclinical vascular damage in adulthood. These findings underscore the importance of early prevention of large PP to reduce future risk of cardiovascular disease.

Arterial stiffness in black African ancestry patients with chronic kidney disease living in Cameroon.

Increased aortic pulse wave velocity (PWV), a direct measure of arterial stiffness (AS) is an independent predictor of cardiovascular events (CVEs) in chronic kidney disease (CKD) patients. This study assessed the patterns of PWV among Cameroonian patients with CKD in whom that marker of early vascular aging has not been explored so far. We enrolled 150 Black African patients (mean age: 52±15 years, 56.7% males) with CKD in a cross-sectional study conducted at Douala General Hospital, Douala, Cameroon. Sociodemographic, anthropometric and biologic variables, blood pressure (BP) and PWV were recorded in all participants. Estimated aortic PWV was measured using a Mobil-O-Graph automatic brachial oscillometric device. PWV increased with aging (P<0.0001), and PWV adjusted for age, sex, body mass index and mean arterial BP (MAP) was higher in non-dialysed (n=90) than in hemodialysed (n=60) patients, even in pre-dialysis: 8.5±2.0 vs. 7.9±1.4 m/s (P=0.026); and in post-dialysis: 8.5±2.0 vs. 7.8±1.5 m/s (P=0.008). The mean PWV of all study participants was 8.2±1.8 m/s, with 61.3% of patients having a PWV ≥8.2 m/s, indicative of subclinical damage to the aorta, which was more pronounced in non-dialysis (67.8%) than in hemodialysis (53.3%) patients (P=0.033). Multivariable analysis performed in all participants revealed that advanced age, MAP and tobacco use were independently associated with PWV (all P<0.05). Our findings suggest increased AS in Cameroonian CKD non-dialyzed as compared to dialyzed patients. Slower PWV in patients on maintenance hemodialysis suggests improvement of aortic distensibility following dialysis. However, further large-scale studies are needed to confirm our findings and to improve understanding of the underlying mechanisms of arterial stiffening in black African ancestry patients with CKD.

EFFECT OF GOLIMUMAB ON IMMUNOLOGICAL MARKERS FOR BONE METABOLISM AND ON ARTERIAL STIFFNESS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Objective: to evaluate the effect of golimumab (GLM) on the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) transmembrane molecular system and arterial stiffness in patients with rheumatoid arthritis (RA).Subjects and methods. Thirty-six patients with RA were examined and randomized into 2 groups based on disease duration (less than or more than 2 years). The serum levels of OPG, and RANKL, were investigated. Dual-energy X-ray absorptiometry and pulse wave contour analysis were performed before and 52 weeks after GLM treatment.Results and discussion. Group 1 patients demonstrated increased serum OPG levels that were on average 3.6 times higher than in the controls (р=0.005) and 2.1 times higher than in Group 2 (р=0.01). In Group 2 patients, the RANKL concentration was 9-fold higher than that in the controls (p=0.001) and 30.6% higher than in Group 1 (p=0.01). The examinees were found to be diagnosed with subclinical damage to the great arteries (increases in augmentation index (AIp), stiffness index (SI), and reflection (RI) index), which progressed with a longer RA duration. After GLM treatment, serum OPG and RANKL levels decreased in Group 1 patients by 2.1- (p&lt;0.001) and 1.7-fold (p&lt;0.01), respectively. In Group 2, the level of RANKL dropped by 32.2% (p&lt;0.01), without significant OPG concentration changes. After GLM treatment, the pulse wave contour analysis parameters in Group 1 did not differ from those in the controls; Group 2 showed significant decreases in AIp by an average of 1.8 times (p&lt;0.01), in SI by 1.2 times (p&lt;0.01), and in RI by 1.6 times (p&lt;0.01).Conclusion. GLM treatment in RA patients is accompanied by a lower imbalance in the RANKL/OPG transmembrane molecular system and exerts a vasoprotective effect on the large elastic vessels (reductions in AIp and SI) and small muscular arteries (a decrease in RI).

Pre-hypertension and subclinical cardiac damage: A meta-analysis of echocardiographic studies

AimThe association between pre-hypertension (pre-HTN) and subclinical cardiac damage remains undefined. We performed a systematic meta-analysis of echocardiographic studies in order to provide a comprehensive information on structural and functional cardiac changes in untreated pre-HTN subjects. DesignStudies were identified by crossing the following search terms: “pre-hypertension”, “high normal blood pressure” “heart” “left ventricular hypertrophy”, “left ventricular function”, “diastolic function”, “left atrial size”, “aortic root size”, “echocardiography.” ResultsA total 73,556 subjects (44,170 normotensive, 17,314 pre-HTN, and 12,072 HTN individuals) of both genders were included in 20 studies. Left ventricular (LV) mass index and relative wall thickness (RWT) were greater in pre-HTN than in normotensives (standard means difference: 0.32 ± 0.07 and 0.30 ± 0.07, respectively, p < 0.001 for both). The E/e′ ratio (0.26 ± 0.02, p < 0.001) and left atrium (LA) diameter were higher (0.55 ± 0.02, p < 0.001) in pre-HTN than in normotensive subjects. HTN subjects showed a greater LV mass index (0.27 ± 0.03, p < 0.001), RWT (0.23 ± 0.02, p < 0.001), increased E/e′ ratio (0.38 ± 0.09, p < 0.001) as well as LA diameter (0.31 ± 0.12, p < 0.001) than pre-HTN subjects. ConclusionsOur meta-analysis suggests that alterations in cardiac structure and function in pre-HTN subjects are intermediate between normotensive and HTN individuals. These findings suggest that pre-HTN may not be a benign entity. If so, early preventive strategies may prevent preclinical cardiac damage.

Does Masked Hypertension Cause Early Left Ventricular Impairment in Youth?

Objectives: Masked hypertension (MH) is not uncommon in the youth and may increase risks of long-term cardiovascular impairment. However, little is known about the subclinical heart damage in this group of patients. Currently, 3-layer speckle tracking imaging based on two-dimensional echocardiography is feasible to detect the early signs of myocardial damage. We therefore aimed to investigate whether subtle changes of cardiac function occurred in the young MH patients by using advanced quantification with layer-specific speckle tracking.Methods: A total of 40 adolescents with MH (age 18 ± 3 years, 73% males) and 40 age-, gender-, race-, and height-matched normotensive volunteers were enrolled in our study. MH was defined as one or more of the ambulatory blood pressure (BP) parameters (24-h, daytime and night-time average BPs) higher than ≥ 95th percentile for gender and height according to the local reference. Both comprehensive two-dimensional echocardiography with layer-specific strain analysis and 24-h ambulatory BP monitoring were performed. Longitudinal strain and circumferential strain in endocardial, mid-myocardial, and epicardial layers were determined accordingly with the dedicated software (EchoPAC software version 201, GE Healthcare, Horten, Norway).Results: Compared with normotensive controls, youths with MH had higher ambulatory pulse rate and left ventricular mass index, and were more obese. Interestingly, similar ventricular volumes and ejection fraction were observed in the study groups, but further analysis with layer-specific strains revealed that endocardial and mid-myocardial longitudinal and circumferential mechanical function were decreased in the young MH subjects when compared to normotensive individuals (all p < 0.05). However, there were no difference regarding radial strain and apical rotation derived from traditional speckle tracking analysis.Conclusion: Subclinical change of LV mechanic function assessed by layer-specific speckle tracking is present in youth with MH despite considered as normal with conventional ways.Thus, MH in youth should be monitored closely instead of labeling as an entirely benign entity.

ASSOCIATION OF SUBCLINICAL VASCULAR DAMAGE WITH DYSLIPIDEMIA IN ST. PETERSBURG POPULATION

Objective: Subclinical vascular damage evaluation is believed to be useful for cardiovascular risk précising in non-high risk patients. Different diagnostic tools suggested for vascular structure and function assessment, while little is known about dyslipidemia impact into its damage development. The aim of the present study was to assess the association of dyslipidemia and different markers of subclinical vascular damage. Design and method: 1592 apparently healthy participants aged 25–65 years were randomly selected from Saint-Petersburg inhabitants (a sample from ESSE-RF epidemiology survey. All participants signed informed consent and filled in the questionnaire regarding risk factors, concomitant diseases and therapy. Fasting lipids, glucose (Abbott Architect 8000) and vital signs were obtained. 191 patients were excluded from the risk estimation due to the presence of cardiovascular complications. Cardio-ankle vascular index (CAVI), carotid-femoral pulse wave velocity (PWV-V) with amorphous probes and ankle-brachial index (ABI) were measured by VaSera VS-1500 (Fukuda). Measurement of intima-media thickness (IMT) was performed by My Sono U6 (Samsung). The subclinical vascular damage was detected, if PWV-V was >10m/s, CAVI >/= 9,0, ABI </= 0,9, IMT > 0,9 mm. Dyslipidemia was defined as cholesterol level > 4,9 mmol/l, or LDL cholesterol > 3,0 mmol/l, or medication prescribed for dyslipidemia. Statistical analysis was performed using SPSS Statistics 20. Results: Majority of participants (955 (76,7%)) had normal values of vascular damage markers.There was no correlation of PWV-V with lipid level, while IMT correlated with cholesterol and HDL level (β = 0,25, 95%CI [0,11–0,62], p = 0,04 and β=−0,15, 95%CI [−0,98-(-0,10)], p = 0,003 respectively). Conclusions: Dyslipidemia seems to be associated with carotid artery atherosclerosis, but not with arterial stiffness. Early detection of carotid atherosclerosis markers should be considered in patients with lipid disorders rather than measurement of arterial stiffness.

DIPPING PROFILE, NIGHTTIME SYSTOLIC BLOOD PRESSURE AND VASCULAR DAMAGE IN PATIENTS WITH RHEUMATOID ARTHRITIS

Objective: Both increased nighttime systolic blood pressure (SBP) and a non-dipping pattern are predictors of adverse cardiovascular outcomes. We investigated dipping profile and nighttime SBP in relationship with subclinical vascular damage in patients with rheumatoid arthritis (RA), a disease characterized by excess cardiovascular risk. Design and method: Patients with RA and non-RA individuals underwent 24-hour ambulatory blood pressure monitoring. Carotid-femoral pulse wave velocity (PWV) was assessed with applanation tonometry as a measure of central arterial stiffness. Carotid atherosclerosis was evaluated from carotid ultrasound by measurement of carotid intima-media thickness (cIMT). Peripheral vascular resistance was estimated from impedance cardiography. Disease-related characteristics were addressed, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease duration and activity, and pain. Results: RA patients (n = 91) exhibited a higher prevalence of non-dipping pattern (64.8 vs 28.0 %, p < 0.001), elevated nighttime SBP (112.6 ± 12.8 vs 105.8 ± 9.7 mmHg, p = 0.001) and a lower degree of dipping (6.5 ± 7.4 vs 13.0 ± 5.6 %, p < 0.001), compared to non-RA individuals (n = 50), whereas both office and daytime SBP did not differ. In the RA group, dipping (%) was inversely associated with PWV (r = –0.218, p = 0.045). Nighttime SBP strongly correlated with all vascular indices, including PWV (r = 0.493, p < 0.001), cIMT (r = 0.407, p < 0.001) and systemic vascular resistance index (r = 0.383, p < 0.001). In addition, nighttime SBP increased with increasing ESR (r = 0.213, p = 0.046), CRP (r = 0.245, p = 0.022), intensity of pain over the past 24-hour hours (r = 0.255, p = 0.042) and disease duration (r = 0.246, p = 0.027). The combination of a non-dipping profile with high nighttime SBP was accompanied by the highest (p = 0.019) PWV (10.0 ± 2.5 m/s), compared to both non-dippers with normal nighttime SBP (7.8 ± 2.1 m/s, p = 0.003) and dippers (8.1 ± 1.9 m/s). In the multivariate analysis for dipping, ESR was identified as an independent predictor (beta = –0.234, p = 0.037), and the same was observed in the multivariate analysis for nighttime SBP (beta = 0.201, p = 0.019). Conclusions: Patients with RA exhibit high prevalence of blunted dipping due to elevated nighttime SBP. Inflammation appears to mediate the observed associations of nighttime SBP and dipping with markers of central and peripheral vascular damage. The combination of a non-dipping profile with abnormal nighttime SBP is accompanied by pronounced subclinical vascular impairment.

Elevated levels of vitamin B12 in chronic stable heart failure: a marker for subclinical liver damage and impaired prognosis.

BackgroundElevated vitamin B12 is a sign for liver damage, but its significance in chronic stable heart failure (HF) is less known. The present study investigated the clinical correlates and prognostic significance of vitamin B12 levels in stable systolic HF.MethodsA total of 129 consecutive patients with HF and 50 control subjects were enrolled. Data regarding demographics, clinical signs, therapeutic and conventional echocardiographic measurements were recorded for all patients. Right-sided HF was defined as the presence of at least one of the typical symptoms (ankle swelling) or specific signs (jugular venous distention or abdominojugular reflux) of right HF. Cox proportional hazards regression analyses were performed to determine the independent prognostic determinants of mortality.ResultsBaseline B12 levels in HF patients (n=129) with and without right sided HF were significantly higher compared to healthy controls (n=50): Median 311 pg/mL and 235 pg/mL vs 198 pg/mL, respectively (P=0.005). Folic acid levels were similar between the study groups. Age, ejection fraction, left atrial size, estimated glomerular filtration rate, and direct and indirect bilirubin levels were significantly correlated to serum B12 level in univariate analysis. In multivariate analysis, independent correlates of B12 were direct bilirubin (R=0.51, P<0.001) and age (R=0.19, P=0.028). Patients with HF were followed-up for a median period of 32 months. Median B12 levels were significantly higher in patients who subsequently died (n=35) compared to survivors, but folic acid was not different between the two groups. ROC analysis showed that B12 values ≥270 pg/mL had 80% sensitivity and 58% specificity for predicting all-cause mortality (area under the curve=0.672, 95% CI=0.562−0.781; P=0.003). However, in Cox regression analysis, only left atrial diameter, level of direct bilirubin, and the presence of abdominojugular reflux were independent predictors of death.ConclusionIncreased B12 in stable HF patients is associated with increased direct bilirubin due to right HF, indicating a cardiohepatic syndrome, but neither B12 nor folic acid are independently associated with mortality.

IN-HOSPITAL BLOOD PRESSURE VARIABILITY AS A PREDICTOR OF RENAL IMPAIRMENT IN PATIENTS WITH MYOCARDIAL INFARCTION

Objective: Recent data have associated blood pressure variability (BPV) with subclinical renal damage, acute renal injury and progression of chronic kidney disease but not in the setting of an acute coronary event. The aim of this study is to determine the impact of in-hospital short-term BPV on future renal impairment in patients suffering an acute myocardial infarction (AMI). Design and method: A total population of57 AMI patients [74.5% male; mean age: 67.56 years;75.4% hypertensives; 28.1% chronic kidney disease (GFR < 60 ml/min on admission)]underwent 24hr ambulatory BP measurement during their hospitalization. At 6months a follow-up was scheduled foreach patient in order to estimate their present renal function. Renal impairment was defined as a decline in GFR value between a discharge and a 6-month visit, which were calculated by using the Cockcroft-Gault Equation. In-hospital BPV was derived by assessment of standard deviation (SD), weighted-SD (SDw), average real variability (ARV) and coefficient of variability (CV). The study population was divided intoa STEMI group (n = 24) and a non-STEMI(n = 33) one. Results: After analysis of BPV indices, 6-month renal impairment was significantly associated with increased SBP CV[odds ratio, 0.467; CI, 0.218–1.003 (P = 0.051)]. This observation was met only in the STEMI group. A multinomial logistic regression analysiswas conducted for this group of patients, in which SBP CV demonstrated a significant prognostic role of renal impairment [odds ratio, 0.623; CI, 0.394–0.987 (P = 0.044)], independently of age, gender and24hr SBP. Conclusions: In the setting of STEMI, assessment of BPV using SBP CV has a prognostic role in the future development of renal dysfunction. This observation, if confirmed by further studies, could influence the therapeutic approach of ACS in terms of BP management.

PRE-HYPERTENSION AND SUBCLINICAL CARDIAC DAMAGE

Abstract Aim The association between pre-hypertension (pre-HTN) and subclinical cardiac damage remains undefined. We performed a systematic meta-analysis of echocardiographic studies in order to provide a comprehensive information on structural and functional cardiac changes in untreated pre-HTN subjects. Design Studies were identified by crossing the following search terms: “pre-hypertension”, “high normal blood pressure” “heart” “left ventricular hypertrophy”, “left ventricular function”, “diastolic function”, “left atrial size”, “aortic root size”, “echocardiography.” Results A total 73,556 subjects (44,170 normotensive, 17,314 pre-HTN, and 12,072 HTN individuals) of both genders were included in 20 studies. Left ventricular (LV) mass index and relative wall thickness (RWT) were greater in pre-HTN than in normotensives (standard means difference: 0.32 ± 0.07 and 0.30 ± 0.07, respectively, p Conclusions Our meta-analysis suggests that alterations in cardiac structure and function in pre-HTN subjects are intermediate between normotensive and HTN individuals. These findings suggest that pre-HTN may not be a benign entity. If so, early preventive strategies may prevent preclinical cardiac damage.

SUBCLINICAL RENAL DAMAGE IS ASSOCIATED WITH A REDUCED CHOROIDAL THICKNESS IN PATIENTS WITH PRIMARY HYPERTENSION

Objective: The retina is considered the easiest accessible window to study the state of the systemic microcirculation, even if the choroid is the most important vascular layer of the eye. Our understanding of the choroid has been greatly increased in last years since the introduction of advanced techniques of optical coherence tomography (OCT). Our study was aimed to assess choroidal thickness by using Swept-Source OCT (SS-OCT) in essential hypertensive patients (EHs) with and without subclinical renal damage (SRD). Design and method: We enrolled 100 EHs of which 65 without kidney damage and 35 with SRD. In all the participants SS-OCT and a routine biochemical work-up were performed. Glomerular filtration rate (GFR) was estimated by the CKD-EPI equation (eGFR). SRD was defined, by the presence of microalbuminuria or eGFR between 30 and 60 mL/min/1.73 m2. OCT measurements were performed according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, that divides the macula into 9 subfields. The circular grid consists of 3 concentric rings. The inner and outer rings are further divided into quadrants: temporal, nasal, superior, and inferior. Furthermore, we calculated the average of the individuals values of the four quadrants separately for the inner and the outer ring. The average of all the 9 regions of the ETRDS grid (including the inner, the outer and the central rings) was also calculated. Results: EHs with SRD showed thinner choroidal thicknesses than those without kidney damage (all p < 0.05), even after adjustment for age (figure). Overall choroidal thickness correlated significantly and directly with eGFR (r = 0.36) and negatively with urinary albumin excretion (r = - 0.39). The association of choroidal thickness with SRD was confirmed in multiple logistic regression analyses once the effect of age, anti-hypertensive therapy and triglycerides was accounted for. The odds ratio of having SRD associated with a standard deviation increase of overall choroidal thickness was 0.43 (0.24–0.75, 95% confidence interval; p = 0.007).Conclusions: Our study confirms the close relationships between changes in ocular microcirculation and renal dysfunction.

Circulating MicroRNAs Implicate Multiple Atherogenic Abnormalities in the Long-Term Cardiovascular Sequelae of Preeclampsia.

BACKGROUNDWomen who have had preeclampsia (PE) are at increased risk for premature cardiovascular disease (CVD). The underlying pathophysiology of this risk remains unclear, but potentially involves subclinical vascular damage or dysfunction. Alterations in the levels of circulating microRNAs may be implicated, as they are known to play pervasive roles in vascular biology. We investigated whether levels of circulating microRNAs are altered between women with premature acute coronary syndrome (ACS), with and without a history of PE.METHODSWomen with premature ACS (age ≤ 55 years) were categorized based on a prior history of PE or normotensive pregnancy. Relative plasma levels of 372 microRNAs were initially assessed by polymerase chain reaction array in a subset of subjects (n = 12–13/group) matched for age, chronic hypertension, dyslipidemia, and smoking status. Candidate microRNAs were then validated in a larger cohort of ACS patients (n = 176).RESULTSMicroRNAs previously linked to angiogenesis (miR-126-3p), inflammation (miR-146a-5p), and cholesterol metabolism (miR-122-5p) were significantly decreased in women with prior PE compared to women with prior normotensive pregnancy (P = 0.002, 0.017, and 0.009, respectively), even after adjustment for chronic hypertension.CONCLUSIONSCirculating levels of miR-126-3p, -146a-5p, and -122-5p were significantly decreased in women with premature ACS who reported prior PE compared to those with prior normotensive pregnancy. These data provide novel insight into potential pathways that may contribute to the increased risk of CVD following PE.

High sodium intake and sodium to potassium ratio may be linked to subsequent increase in vascular damage in adults aged 40 years and older: the Korean multi-rural communities cohort (MRCohort)

Subclinical vascular damage is a chronic intermediate process in cardiovascular disease (CVD) and high sodium (Na) has been regarded as an adverse factor in subclinical vascular health; however, the longitudinal relationship between Na intake and subclinical vascular damage has not been studied. We aimed to evaluate the longitudinal relationship of dietary Na intake and sodium to potassium ratio (Na:K) with brachial-ankle pulse wave velocity (baPWV) and carotid intima media thickness (cIMT) in healthy adults aged 40years and older in Korea. The present study was based on participants (n = 2145 for baPWV analysis and n = 2494 for cIMT analysis) who visited three times during 2005-2013 (median 5.3years of follow-up). We used both dietary Na intake and Na:K at baseline and its average (baseline, 2nd, 3rd), which was obtained from food frequency questionnaire (FFQ) as exposure at every visit. baPWV and cIMT levels at the third visit and change from baseline to the third visit were used to represent the level of subclinical vascular damage. After adjustment for potential confounders, significant positive relationships between dietary Na intake and both baPWV3rd and cIMT3rd were observed (baPWV: p for trend ≤ 0.0001 for Naaverage; cIMT: p for trend = 0.013 for Naaverage). Compared with Na:Ks less than 1.0, the levels of both baPWV and cIMT were higher for participants with Na:Ks over 1.0 (baPWV: p for trend = 0.0002 for Na:Kaverage; cIMT: p for trend = 0.005 for Na:Kaverage). Similar significant trends were shown in relationships between dietary Na intake and Na:K and changes in baPWV and cIMT levels. In conclusion, dietary Na intake and Na:K may be positively linked to subsequent baPWV and cIMT levels in adults aged 40years and older in Korea. Our findings may provide informative evidence on subclinical vascular damage, particularly for populations with relatively high dietary Na intake and low dietary K intake.

Intervention of integrative medicine treatment has impact on serum levels of ET-1, TNF-α, MLT in RA-CVD.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that can destroy peripheral joints. However, very little is known regarding specific biological marker for RA in Chinese patients. In this study, we determined the serum biomarkers and clinical features of RA-CVD. We also evaluated the short-term efficacy of routine RA treatment combined with integrative medicine treatment on RA-CVD. We found that anti-cyclic citrullinated peptide (CCP) and disease activity score in 28 joints (DAS28) are associated with risks of cardiovascular disease (CVD) in RA. And, melatonin (MLT) may play a negative regulatory role in cardiovascular damage in patients with RA. Furthermore, endothelin (ET-1) and inflammatory markers may be subclinical cardiovascular damages in RA. Moreover, of the 17 patients with RA-CVD, test results of ET-1, TNF-α and OSCAR after integrative medicine treatment were significantly decreased than before treatment. Collectively, our results provide a therapeutic potential of integrative medicine to the treatment of RA-CVD.

NEPHROPROTECTIVE EFFECTS OF LISINOPRIL IN THE THERAPY OF HYPERTENSIVE PATIENTS WITH OBESITY

Aim. To investigate the dynamics of biomarkers of early renal damage in patients with hypertension (HT) and obesity treated with lisinopril and diet therapy. Material and methods. The study included 120 people aged 25 to 55 years (90 patients with HT in combination with obesity and 30 HT patients without obesity). Control group was consisted of 50 healthy respondents without obesity. All HT patients received therapy with lisinopril at a dose of 10-40 mg per day with titration to target blood pressure (BP) values, patients with obesity – additionally diet therapy. Initially and after 6 months we investigated clinical and biochemical parameters, levels of leptin, resistin, cystatin C in blood serum and urine, albuminuria, NGAL (neutrophil gelatinase associated lipocalin) and interleukin 18 (IL-18) in the urine. Results. We identified the relationships between the serum cystatin C and BP, leptin, resistin, insulin-resistance index (HOMA-IR) and also metabolic indicators. In this study we revealed relationships of subclinical tubular dysfunction markers (urinary cystatin C, IL-18, NGAL) with carbohydrate and lipid metabolism, BP, hormonal activity of adipose tissue. The achievement of target BP values, normoalbuminuria and improving the glomerular filtration rate (GFR) were found after 6 months. The decrease in serum cystatin C in groups was seen: in Group 1 – from 1112 [757.0; 1400.0] to 797 [754; 825] ng/ml (р=0.001), in Group 2 – from 990 [700.0;1110.0] to 791 [770;900] ng/ml (р=0.03). Decrease in markers of tubular dysfunction was identified only in patients who reduced the body weight: urine cystatin C − from 33.0 [18.5; 50.0] to 24[15.3; 60.0] ng/ml (р=0.04) and IL-18 – from 0.33 [0.18; 0.41] to 0.21 [0.14; 0.43] pg/ml (р=0.04). Greater reduction in tubular dysfunction markers excretion was observed in the subgroup of patients with weight loss more than 5% but less than 10% of the initial value. Conclusion. The obtained relationships between markers of subclinical tubular damage and carbohydrate, lipid metabolism and adipokines prove the contribution of adipose tissue to the formation of tubular damage in patients with HT associated with obesity. Antihypertensive therapy with lisinopril contributes to the achievement of target BP values, improvement of metabolic parameters, increase in GFR, achievement of normoalbuminuria, whereas body weight loss in HT patients with obesity additionally contributes to the reduction in the manifestations of tubular dysfunction.