George Pavlidis

Increased benefit of interleukin-1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis.

Background—We investigated the effects of anakinra, an interleukin-1 receptor antagonist, on coronary and left ventricular function in coronary artery disease (CAD) patients with rheumatoid arthritis. Methods and Results—In a double-blind crossover trial, 80 patients with rheumatoid arthritis (60 with CAD and 20 without) were randomized to a single injection of anakinra or placebo and after 48 hours to the alternative treatment. At baseline and 3 hours after treatment, we assessed (1) flow-mediated dilation of brachial artery; (2) coronary flow reserve, ejection fraction, systemic arterial compliance, and resistance by echocardiography; (3) left ventricular global longitudinal and circumferential strain, peak twisting, untwisting velocity by speckle tracking; and (4) interleukin-1&bgr;, nitrotyrosine, malondialdehyde, protein carbonyl, and Fas/Fas ligand levels. At baseline, patients with CAD had 3-fold higher interleukin-1&bgr;, protein carbonyl, higher nitrotyrosine, malondialdehyde, and Fas/Fas ligand than non-CAD (P<0.05). After anakinra, there was a greater improvement of flow-mediated dilation (57±4% versus 47±5%), coronary flow reserve (37±4% versus 29±2%), arterial compliance (20±18% versus 2±17%), resistance (−11±19% versus 9±21%), longitudinal strain (33±5% versus 18±2%), circumferential strain (22±5% versus 13±5%), peak twisting (30±5% versus 12±5%), untwisting velocity (23±5% versus 13±5%), ejection fraction (12±5% versus 0.5±5%), apoptotic and oxidative markers, and, in particular, of protein carbonyl (35±20% versus 14±9%) in CAD than in non-CAD patients (P<0.01). No changes in the examined markers were observed after placebo. Conclusions—Interleukin-1 inhibition causes a greater improvement in endothelial, coronary aortic function in addition to left ventricular myocardial deformation and twisting in rheumatoid arthritis patients with CAD than in those without. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01566201.

Is Arterial Hypertension Control Enough to Improve Aortic Stiffness in Untreated Patients With Hypertension? A 3-Year Follow-Up Study:

Aortic stiffness is an important determinant of cardiovascular risk. We studied the long-term influence of successful antihypertensive treatment after a 3-year follow-up, regarding aortic stiffness improvement from baseline evaluation in never treated middle-aged patients with mild to moderate essential hypertension. In 132 patients with hypertension, aortic stiffness was evaluated by carotid–femoral artery pulse wave velocity (PWV). Patients with 24-hour mean systolic and diastolic blood pressure ≤130/80 mm Hg after treatment at reevaluation were considered as well controlled. The PWV after treatment was significantly increased in all patients with hypertension (P < .01) and uncontrolled patients with hypertension (P < .001), remained unchanged in controlled patients with hypertension, and decreased in controlled patients with hypertension with baseline PWV ≥12.4 m/s (P = .004), independent of the corresponding blood pressure (BP) decrease. Our study provides evidence that successful antihypertensive treatment leads to PWV improvement when baseline aortic stiffness level is at least moderately increased. The magnitude of observed PWV decrease is independent of the corresponding BP decrease.

Early detection of left ventricular dysfunction in first-degree relatives of diabetic patients by myocardial deformation imaging: The role of endothelial glycocalyx damage

BACKGROUND First-degree relatives of type-2 diabetes patients (FDR) present insulin resistance. We investigated whether FDR and dysglycaemic subjects demonstrate abnormal endothelial glycocalyx and LV deformation during postprandial hyperglycemia. METHODS We studied 40 FDR with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic). At 0 and 120min of OGTT we measured: a) LV longitudinal strain (LS) of subendocardial, mid-myocardial and subepicardial layers, global LS (GLS), peak twisting (pTw), untwisting velocity (pUtwVel), by speckle tracking echocardiography b) perfused boundary region (PBR) of the sublingual arterial microvessels; high PBR values represent reduced glycocalyx thickness. Insulin resistance was evaluated using insulin sensitivity index (ISI). RESULTS ISI was related with baseline PBR, GLS and pTw in all subjects (p<0.05). Compared to normoglycaemics, FDR and dysglycaemics had higher PBR, lower ISI, GLS (-18.4±2.6 and -16.8±2.0 vs. -19.2±2.4%), subendocardial LS (-19.0±4.2 and -17.9±3.0 vs. -20.1±3.4%), pTw (14.4±4.4 and 15.6±6.4 vs. 16.9±6.5deg) and pUtwVel (p<0.05 for all comparisons). A GLS<-18% identified FDR with LV dysfunction (p=0.016). Post-OGTT, GLS and the subendocardial LS decreased while pTw and pUtwVel increased in FDR and dysglycaemics (p<0.05) indicating prevalence of the motion of the subepicardial over a dysfunctioning subendocardial myocardial helix. Increased PBR was related with impaired deformation markers at baseline and 120min of OGTT (p<0.05). CONCLUSION First-degree relatives and dysglycaemics have reduced glycocalyx thickness related with impaired LV longitudinal, twisting-untwisting function. Postprandial hyperglycemia when combined with insulin resistance causes LV longitudinal dysfunction leading to increased LV twisting.

Electronic Cigarette Smoking Increases Arterial Stiffness and Oxidative Stress to a Lesser Extent Than a Single Conventional Cigarette: An Acute and Chronic Study

The electronic cigarette (e-cig) has been proposed as a safer alternative than tobacco cigarettes (con-cigs)1,2 and as a bridge to smoking cessation. We aimed to examine its effects (1) on aortic stiffness as assessed by pulse wave velocity (PWV) and augmentation index (AIX75), (2) exhaled CO concentration, and (3) oxidative stress as assessed by malondialdehyde (MDA) plasma concentrations, both acutely and after 1 month of use. We studied 70 current smokers (age: 48±5 years, 56% female, 24±8 cigarettes/d, 30±7 pack-years, no other atherosclerotic risk factors or any medication) attending the hospital’s smoking cessation unit. Of those, 35 were assigned to use nicotine-free e-cig fluid (NOBACCO eGo Epsilon BDC 1100, eGo battery, 1100 mAh, operating at 3.9 V) during the acute-phase protocol, whereas the remaining 35 were assigned to an e-cig fluid with nicotine concentration of 12 mg/mL (propylene glycol 74.3%, glycerin 20%, flavoring 4.5%, nicotine 1.2%). All subjects underwent a baseline sham smoking for 7 minutes (inhaling on a nonlighted cigarette) and then were randomly assigned to smoke a single con-cig or vape an e-cig for 7 minutes (simulating the duration of a normal cigarette smoking). …

Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in PsoriasisCLINICAL PERSPECTIVE

Background— Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis. Methods and Results— One hundred fifty psoriasis patients were randomized to receive an anti–IL-12/23 (ustekinumab, n=50), anti–tumor necrosis factor-a (TNF-&agr;; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-&agr;, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: −17.7% versus −19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-&agr;, and IL-6 post-treatment (P<0.05). Compared with anti–TNF-&agr; and cyclosporine, anti–IL-12/23 treatment resulted in a greater improvement of global longitudinal strain (25% versus 17% versus 6%,), LV twist (27% versus 17% versus 1%), %untwMVO (31% versus 27% versus 17%), and coronary flow reserve (14% versus 11% versus 4%), as well as a greater reduction of IL-12 (−25% versus −4% versus −2%), malondialdehyde (−27% versus +5% versus +26%), and NT-proBNP(−26% versus −13.6% versus 9.1%) and increase of fetuin-a (P<0.01). Pulse wave velocity and augmentation index were improved only after anti–IL-12/23 treatment and correlated with changes in global longitudinal strain, LV twisting–untwisting (P<0.05). Conclusions— In psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-&agr; inhibition or cyclosporine treatment. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02144857.

The Association of Elevated HDL Levels With Carotid Atherosclerosis in Middle-Aged Women With Untreated Essential Hypertension:

High-density lipoprotein cholesterol (HDL-C), a negative risk factor, is positively associated with a decreased risk of coronary heart disease. We investigated the association between high HDL-C levels and target organ damage (TOD) in never treated women with hypertension. We measured HDL-C levels in 117 women followed by estimation of TODs, that is, pulse wave velocity, microalbuminuria, left ventricular mass index, coronary flow reserve, and carotid intima–media thickness (cIMT). Women were divided into 2 groups (HDLH and HDLL), regarding HDL-C quartiles (upper quartile vs the first 3 lower quartiles). In HDLH group (HDL ≥70 mg/dL), cIMT was nonindependently, negatively related to HDL-C (ρ = −.42, P < .05). Using receiver –operating characteristic curve (ROC) analysis in the HDLH group, we concluded that the cutoff value of HDL ≥76.5 mg/dL moderately predicted the absence of carotid atherosclerosis (area under the curve: 0.77, P = .02; confidence interval: 0.57-0.97; sensitivity 73% and specificity 67%). Increased HDL-C may predict the absence of carotid atherosclerosis in middle-age women with untreated essential hypertension and consequently contribute to total cardiovascular risk estimation and treatment planning.

Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives

We investigated the association of endothelial glycocalyx damage with arterial stiffness, impairment of coronary microcirculatory function, and LV myocardial deformation in 320 untreated hypertensives and 160 controls. We measured perfused boundary region (PBR) of the sublingual microvessels, a marker inversely related with glycocalyx thickness, coronary flow reserve (CFR), and Global Longitudinal strain (GLS) by echocardiography, pulse wave velocity (PWV), and central systolic blood pressure (cSBP). Hypertensives had higher PBR, PWV cSBP, and lower CFR and GLS than controls (P < .05). In hypertensives, increased PBR was associated with increased cSBP, PWV, and decreased CFR and GLS after adjustment for age, sex, BMI, smoking LV mass, heart rate, hyperlipidemia, and office SBP (P < .05). PBR had an additive value to PWV, CFR, and office SBP for the prediction of abnormal GLS (x2 = 2.4‐3.8, P for change = .03). Endothelial glycocalyx is impaired in untreated hypertensives and is related to arterial stiffness, coronary, and myocardial dysfunction.

Severity of Alopecia Predicts Coronary Changes and Arterial Stiffness in Untreated Hypertensive Men

An association between androgenic alopecia (AGA), coronary artery disease, and hypertension has been reported in previous epidemiological studies. The authors evaluated the relationship of target organ damage caused by hypertension with AGA in 101 newly diagnosed and untreated hypertension men with mild to moderate AGA (AGAm), severe AGA (AGAs), and non‐AGA. Pulse wave velocity (PWV), office and 24‐hour pulse pressure (PP), carotid intima‐media thickness (IMT), left ventricular hypertrophy (LVH), coronary flow reserve (CFRd), and AGA severity by Hamilton‐Norwood scale were estimated. CFRd was significantly impaired in AGAs patients compared with AGAm (P=.007) and non‐AGA patients (P=.02). No differences were found within groups regarding PWV, PP, IMT, and LVH. AGA severity was related to CFRd (independently) and PP while AGA duration and age of onset were related to CFRd and PP, respectively. The authors conclude that impaired coronary microcirculation and aortic stiffness might precede the appearance of significant stenotic coronary lesions in hypertensive patients with severe AGA. In addition, hypertensive patients with severe and early AGA onset seem to be exposed to an augmented cardiovascular risk.

HDL cholesterol levels and endothelial glycocalyx integrity in treated hypertensive patients

Endothelial dysfunction indicates target organ damage in hypertensive patients. The integrity of endothelial glycocalyx (EG) plays a vital role in vascular permeability, inflammation and elasticity, and finally to cardiovascular disease. The authors aimed to investigate the role of increased HDL cholesterol (HDL‐C) levels, which usually are considered protective against cardiovascular disease, in EG integrity in older hypertensive patients. The authors studied 120 treated hypertensive patients older than 50 years were divided regarding HDL‐C tertiles in group HDLH (HDL‐C ≥ 71 mg/dL, upper HDL‐C tertile) and group HDLL (HDL‐C < 71 mg/dL, two lower HDL‐C tertiles). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranging from 5 to 9 µm) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non‐invasive accurate index of reduced EG thickness. PBR 5‐9 was significantly decreased in group HDLH (P = 0.04). In the whole population, HDL‐C was inversely but moderately related to PBR 5‐9 (r = −0.22, P = 0.01). In a multiple linear regression analysis model, using age, BMI, smoking habit, HDL‐C, LDL‐C, and office SBP, as independent variables, the authors found that BMI (β = 0.25, P = 0.006) independently predicted PBR 5‐9 in the whole population. In older hypertensive patients, HDL‐C ranging between 71 and 101 mg/dL might moderately protect EG and subsequently endothelial function. Future studies in several groups of low‐ or high‐risk hypertensives are needed in order to evaluate the beneficial role of extremely elevated HDL‐C regarding cardiovascular risk evaluation as well as endothelial glycocalyx as a novel index of target organ damage in essential hypertension.

Bilateral sphenopalatine ganglion block reduces blood pressure in never treated patients with essential hypertension. A randomized controlled single-blinded study

BACKGROUND Sympathetic fibers connect sphenopalatine ganglion (SPG) with the central nervous system. We aimed to study the effect of SPG block in blood pressure (BP) in never treated patients with stage I-II essential hypertension. METHODS We performed bilateral SPG block with lidocaine 2% in 33 hypertensive patients (mean age 48±12years, 24 men) and a sham operation with water for injection in 11 patients who served as the control group (mean age 51±12years, 8 men). All patients have been subjected to 24h ambulatory blood pressure monitoring prior and a month after the SBG block in order to estimate any differences in blood pressure parameters. We defined as responders to SBG block those patients with a 24h SBP decrease ≥5mmHg. RESULTS We found that 24h and daytime DBP (p=0.02) as well as daytime DBP load (p=0.03) were decreased in the study group a month after SPG block. In addition, a significant response was noted in 12/33 responders (36%) regarding: a. SBP and DBP during overall 24h and daytime (p<0.001) and night-time periods, b. pre-awake and early morning SBP and c. SBP (daytime and night-time) and DBP (daytime) load. No differences regarding BP were found in the sham operation group. CONCLUSIONS SPG block is a promising, minimally invasive option of BP decrease in hypertensives, probably through SNS modulation. Additionally, due to its anesthetic effect, SPG block might act as a method of selection for those hypertensive patients with an activated SNS before any other invasive antihypertensive procedure.