Association of sleep duration and quality with immunological response after vaccination against severe acute respiratory syndrome coronavirus-2 infection.

Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer-BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38-54) years and body mass index of 24·84 (22.6-28.51) kg/m2 were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6-7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = -0.178, p < 0.001), poor sleep quality (r = -0.094, p < 0.05), insomnia (r = -0.098, p < 0.05), and nap frequency per week (r = -0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination.

Impaired Human Sexual and Erectile Function Affecting Semen Quality, in Obstructive Sleep Apnea: A Pilot Study.

Obstructive sleep apnea (OSA) is a rising problem, with important implications for public health. Recent evidence has revealed a link between OSA and reduced male fertility. We investigated the association between OSA and sexual and erectile function, as well as semen quality, and the effect of treatment by continuous positive airway pressure (CPAP). A total of 41 male subjects, who underwent polysomnography for suspected OSA, participated in the study. Erectile and sexual function were assessed with the 15-item International Index of Erectile Function (IIEF-15) questionnaire, blood samples, and sperm analysis. OSA patients after the initiation of CPAP treatment were followed for a period of 1 year. Thirty-two patients were diagnosed with OSA, and nine subjects without OSA were used as a control group. OSA patients demonstrated significantly impaired erectile function, reduced testosterone levels, and lower semen quality. Multivariable regression analysis showed that BMI and IIEF score were independent determinants of AHI. Sexual function improved after a year of CPAP therapy in OSA patients. This study provides further evidence regarding the association between OSA and erectile function impairment, as well as semen quality. Longitudinal adherence to CPAP treatment has a beneficial effect on erectile function.

Beta Blockers and Chronic Obstructive Pulmonary Disease (COPD): Sum of Evidence.

Approximately half a century has passed since the discovery of beta-blockers. Then, their prime therapeutic purpose was to treat angina and cardiac arrhythmias; nowadays, beta-blockers' usage and effectiveness are extended to treat other cardiovascular diseases, such as hypertension, congestive heart failure, and coronary artery disease. Safety concerns were raised about beta- blockers and their use for chronic obstructive pulmonary disease (COPD) patients with concurrent cardiovascular disease. After thorough research of the literature, this review summarizes the evidence proving that beta-blockers not only might be well tolerated in COPD patients, but they might also have a beneficial effect in this group of patients.

Complex sleep apnea after full-night and split-night polysomnography: the Greek experience.

PURPOSE: Treatment-emergent central sleep apnea (TE-CSA) is defined as the emergence or persistence of central respiratory events during the initiation of positive airway pressure (PAP) without a back-up rate in obstructive sleep apnea (OSA) patients and after significant resolution of obstructive events. Previous studies have estimated a prevalence from 0.56 to 20.3%. The aim of this study was to establish the prevalence of TE-CSA in a Greek adult population. METHODS: One thousand fifty nine patients with newly diagnosed OSA, who were referred to the Sleep Disorders Center of Evangelismos Hospital of Athens over an 18-month period, were included in this study. A split-night polysomnography (PSG), or two formal overnight PSGs (diagnostic and continuous PAP (CPAP) titration study), were performed. RESULTS: Patients with OSA were divided in two groups; the first group included 277 patients, who underwent two separate studies (diagnostic and CPAP titration study), and the second group 782 patients, who underwent split-night studies. The prevalence of TE-CSA in the first group was 2.53% (7 patients), and in the second group was 5.63% (44 patients). CONCLUSIONS: The prevalence of TE-CSA in Greece was lower compared to most previous reported studies. The significant variation in the prevalence of TE-CSA between different centers throughout the world is mainly associated with the used diagnostic criteria as well as methodological and technical aspects.

Cardiovascular Risk Factors Accelerate Progression of Vascular Aging in the General Population: Results From the CRAVE Study (Cardiovascular Risk Factors Affecting Vascular Age).

Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular risk. We hypothesized that the number of cardiovascular risk factors determines the progression of vascular aging. One hundred forty-two subjects (mean age 51.9 years, 94 men) without established cardiovascular disease were investigated in 2 examinations over a 2-year period. Subjects were classified at baseline according to their number of risk factors (from 0 to 2 and more). Subjects had determinations of carotid-femoral pulse wave velocity, aortic augmentation index, brachial flow-mediated dilatation, and common carotid intima-media thickness and their annual absolute changes were calculated. Subjects with more risk factors had a gradual higher annual progression of pulse wave velocity (0.092 m/s/y for 0, 0.152 m/s/y for 1, and 0.352 m/s/y for 2 and more; P=0.007). Patients with both hypertension and dyslipidemia have 4× higher annual progression rate compared with subjects without these risk factors (0.398 m/s/y versus 0.102 m/s/y). When only subjects 55 years old and under were considered, the progression rate of augmentation index was higher in subjects with more risk factors (1.15%/y versus 1.50%/y versus 2.99%/y, respectively; P=0.037). No association was found with the annual change of flow-mediated dilatation or carotid intima-media thickness. In the general population, increasing number of risk factors is associated with accelerated deterioration of specific indices of vascular aging, such as pulse wave velocity and augmentation index; in contrast, flow-mediated dilatation and carotid intima-media thickness are insensitive to such changes. Accordingly, the former may be more useful for gauging vascular aging.

Survival in Idiopathic pulmonary fibrosis acute exacerbations: the non-steroid approach.

BACKGROUND: Idiopathic pulmonary fibrosis acute exacerbation (IPF-AE) constitutes IPF's most devastating event, representing the unexpected superimposition of diffuse alveolar damage of unknown etiology. Guidelines recommend high-dose steroids treatment despite unproven benefit. We hypothesized that previous immunosuppression and the administration of high-dose steroids adversely affect IPF-AE outcome. METHODS: We studied all consecutive patients hospitalized in our department for IPF deterioration from 2007 to June 2013. Our protocol consisted of immediate cessation of immunosuppression (if any), best supportive care, broad-spectrum antimicrobials and thorough evaluation to detect reversible causes of deterioration. Patients were followed-up for survival; post-discharge none received immunosuppression. RESULTS: Twenty-four out of 85 admissions (28%) fulfilled IPF-AE criteria. IPF-AE were analyzed both as unique events and as unique patients. As unique events 50% survived; 3 out of 12 (25%) in the group previously treated with immunosuppression whereas nine out of 12 (75%) in the group not receiving immunosuppression (p = 0.041). As unique patients 35.3% survived; 3 out of 6 (50%) in the never treated group whereas three out of 11 (27.3%) in the group receiving immunosuppression (p = 0.685). The history of immunosuppression significantly and adversely influenced survival (p = 0.035). Survival was greater in the never treated group compared to the immunosuppressed patients (p = 0.022). Post-discharge, our IPF-AE survivors had an 83% 1-year survival. CONCLUSIONS: By applying the above mentioned protocol half of our patients survived. The history of immunosuppression before IPF-AE adversely influences survival. Avoiding steroids in IPF patients may favor the natural history of the disease even at the moment of its most devastating event.

Sleep oxygen desaturation predicts survival in idiopathic pulmonary fibrosis.

BACKGROUND: Recent studies suggest poor sleep quality in patients with idiopathic pulmonary fibrosis (IPF). However, so far, the impact of IPF-related sleep breathing disorders (SBDs) on survival has not been extensively studied. METHODS: In a cohort of 31 (24 males) treatment-naïve, newly diagnosed consecutive IPF patients, we prospectively investigated the relationship of SBD parameters such as apnea-hypopnea index (AHI), maximal difference in oxygen saturation between wakefulness and sleep (maxdiff SpO2), and lowest sleep oxygen saturation (lowest SpO2) with clinical (survival, dyspnea, daytime sleepiness), pulmonary function, submaximal (6-min walk test [6MWT]) and maximal exercise variables (cardiopulmonary exercise test [CPET]), and right ventricular systolic pressure (RVSP). RESULTS: Sleep oxygen desaturation exceeded significantly that of maximal exercise (p < 0.001). Maxdiff SpO2 was inversely related to survival, DLCO%, and SpO2 after 6MWT, and directly with dyspnea, AHI, and RVSP. The lowest SpO2 was directly related to survival and to functional (TLC%, DLCO%) as well as submaximal and maximal exercise variables (6MWT distance, SpO2 after 6MWT, peak oxygen consumption/kg, SpO2 at peak exercise), while an inverse association with dyspnea score, AHI, and RVSP was observed. CONCLUSIONS: Our findings provide evidence that intermittent sleep oxygen desaturation significantly exceeds that of maximal exercise and is associated with survival in IPF patients. Furthermore, they imply the existence of a link between lung damage and apnea events resulting to the induction and severity of intermittent sleep oxygen desaturation that aggravate pulmonary arterial hypertension and influence IPF survival.

Bronchiolitis: adopting a unifying definition and a comprehensive etiological classification.

Bronchiolitis is an inflammatory and potentially fibrosing condition affecting mainly the intralobular conducting and transitional small airways. Secondary bronchiolitis participates in disease process of the airways and/or the surrounding lobular structures in the setting of several already defined clinical entities, mostly of known etiology, and occurs commonly. Primary or idiopathic bronchiolitis dominates and characterizes distinct clinical entities, all of unknown etiology, and occurs rarely. Secondary bronchiolitis regards infections, hypersensitivity disorders, the whole spectrum of smoking-related disorders, toxic fumes and gas inhalation, chronic aspiration, particle inhalation, drug-induced bronchiolar toxicities, sarcoidosis and neoplasms. Idiopathic or primary bronchiolitis defines clinicopathologic entities sufficiently different to be designated as separate disease entities and include cryptogenic constrictive bronchiolitis, diffuse panbronchiolitis, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, neuroendocrine hyperplasia in infants, bronchiolitis obliterans syndrome in lung and allogeneic hematopoietic cell transplantation, connective tissue disorders, inflammatory bowel disease and bronchiolitis obliterans organizing pneumonia. Most of the above are pathological descriptions used as clinical diagnosis. Acute bronchiolitis, though potentially life threatening, usually regresses. Any etiology chronic bronchiolitis contributes to morbidity and/or mortality if it persists and/or progresses to diffuse airway narrowing and distortion or complete obliteration. Bronchiolitis in specific settings leads to bronchiolectasis, resulting in bronchiectasis.

Combined pulmonary fibrosis and emphysema.

The advent of computed tomography permitted recognition of the coexistence of pulmonary fibrosis and emphysema (CPFE). Emphysema is usually encountered in the upper lobes preceding fibrosis of the lower lobes, and patients are smokers, predominantly male, with distinct physiologic profile characterized by preserved lung volumes and markedly reduced diffusion capacity. Actually, the term CPFE is reserved for the coexistence of any type and grade of radiological pulmonary emphysema and the idiopathic usual interstitial pneumonia computed tomography pattern as well as any pathologically confirmed case. CPFE is complicated by pulmonary hypertension, lung cancer and acute lung injury and may present different outcome than that of its components.

Common single nucleotide polymorphisms of the p22phox NADPH oxidase subunit do not influence aortic stiffness in young, healthy adults.

INTRODUCTION: Aortic stiffness is a valuable biomarker for stratifying cardiovascular risk. NADPH oxidase regulates oxidative status in vessels; its single nucleotide polymorphisms (SNPs) modify the redox state of carriers and may lead to noxious structural alterations and affect the vasomotor properties of arteries. We hypothesized that genetic variability of NADPH oxidase would be accompanied by differences in aortic stiffness; to this end, we explored the interplay of pulse wave velocity (PWV), a measure of aortic stiffness, with common SNPs of the CYBA gene that encodes the p22phox subunit of NADPH oxidase. METHODS: 289 young, healthy adults were studied. The -930A/G, A640G and C242T CYBA SNPs were genotyped and PWV was measured. Differences in PWV across genotypes were examined in unadjusted models and after adjustment for confounders. RESULTS: Genetic variability of the examined SNPs did not result in changes of aortic stiffness. In unadjusted models, PWV did not differ across genotypes for the -930A/G (p=0.20), A640G (p=0.65) or C242T SNP (p=0.50). In stepwise multiple linear regression analysis only sex, age and systolic blood pressure emerged as independent predictors of PWV. CONCLUSIONS: Common genetic variants of NADPH oxidase do not influence aortic stiffness in young, healthy adults.

Association between retinal microcirculation and aortic stiffness in hypertensive patients.

BACKGROUND: The fundoscopic examination of hypertensive patients, an established hypertension-related target organ damage, tends to be underutilized in clinical practice. We sought to investigate the relationship between retinal alterations and aortic stiffness, an independent predictor of cardiovascular morbidity and mortality. METHODS: Our population consisted of 197 consecutive essential hypertensive patients (age 60 ± 13 years, 115 females) without overt cardiovascular disease. All subjects underwent fundoscopy examination and were distributed to four groups according to Scheie's grading system. Aortic stiffness was evaluated by carotid-femoral pulse wave velocity with a validated device (Complior). RESULTS: The four groups (Scheie's grades 0-3: including 24, 75, 74, 24 patients respectively) did not differ with regard to age, gender and their metabolic profile. Patients with higher Scheie's category had higher values of pulse wave velocity (8.2 ± 1.5, 8.9 ± 1.7, 9.3 ± 1.8, 9.8 ± 2.1m/s respectively, p=0.001). Multivariable regression analysis showed that age, fundus classification and systolic arterial pressure were independent determinants of pulse wave velocity. CONCLUSION: Hypertensive subjects exhibit a progressive stiffening of the aorta in parallel with the progression of retinal alterations according to Scheie's scale. Further studies are needed to clarify involved pathophysiological mechanisms and explore possible causal relationships.

Association of serum uric acid level with aortic stiffness and arterial wave reflections in newly diagnosed, never-treated hypertension.

BACKGROUND: Serum uric acid (UA) plays a key role in the development and progression of hypertension. We investigated the association of UA levels and indices of arterial function in a cohort of newly diagnosed, never-treated hypertensive subjects. METHODS: One thousand two hundred and twenty-five patients with a new diagnosis of mild to moderate arterial hypertension for which they had never received treatment were enrolled in the study (mean age 52.9 years, 728 men). Serum UA, carotid-femoral pulse-wave velocity (cfPWV), an index of aortic stiffness and augmentation index (AIx), a composite marker of wave reflections and arterial stiffness were measured. RESULTS: In univariable analysis, UA levels correlated with cfPWV (r = 0.23, P < 0.001) and AIx (r = -0.24, P < 0.001). In multiple linear regression analysis, an independent positive association of cfPWV with UA levels was observed after adjusting for confounders (standardized regression coefficient ß = 0.169, P < 0.001, adjusted R² = 0.402), indicating an increase in aortic stiffness with higher values of UA. In contrast, an independent negative association of AIx with UA levels was observed after adjusting for confounders (standardized regression coefficient ß = -0.064, P = 0.011, adjusted R² = 0.557), indicating a decrease in wave reflections with higher values of UA. In gender-specific analyses, UA positively correlated with cfPWV in both genders, whereas a negative correlation with AIx existed only in females. CONCLUSIONS: Serum UA levels are independently associated with aortic stiffening and wave reflections in never-treated hypertensives. Future studies are warranted in order to explore its exact role on arterial function in the hypertensive setting.

Increased arterial stiffness and impaired endothelial function in nonalcoholic Fatty liver disease: a pilot study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease both in the general and pediatric population and has been associated with increased cardiovascular risk. Arterial function and early atherosclerotic changes are markers of cardiovascular disease and independent predictors of the corresponding risk. Through a global approach, we investigated the relationships between NAFLD and functional arterial changes and early atherosclerosis. METHODS: A total of 23 consecutive patients (mean age 55 ± 14 years, 11 males) with biopsy evidence of NAFLD and 28 control subjects matched for age, gender, body mass index, and other cardiovascular risk factors participated in the study. RESULTS: Compared to controls, NAFLD subjects had significantly higher carotid-femoral pulse wave velocity (PWV; 8.2 ± 1.3 m/s vs. 6.9 ± 1.3 m/s, P = 0.001), higher carotid intima-media thickness (IMT; 0.79 ± 0.18 mm vs. 0.67 ± 0.13 mm, P = 0.01), and reduced flow-mediated dilatation (FMD; 1.92 ± 2.11% vs. 4.8 ± 2.43%, P < 0.001). In multivariable analysis, presence of NAFLD was an independent determinant of both PWV and FMD, whereas leptin was an independent determinant of PWV (B = 0.036, P < 0.05), and adiponectin was independently associated with FMD (B = 0.104, P < 0.05). In addition, histological activity of liver disease expressed by the global Brunt Grade was associated independently with FMD (B = -1.054, P < 0.05). CONCLUSIONS: NAFLD is associated with arterial stiffness and endothelial dysfunction. Given the important independent prognostic role of these arterial indexes, these findings have important implications for increased cardiovascular risk in patients with NAFLD.

The effect of p22(phox) -930A/G, A640G and C242T polymorphisms of NADPH oxidase on peripheral and central pressures in healthy, normotensive individuals.

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces superoxide, thus regulating redox state in the vessel wall. Three single-nucleotide polymorphisms (SNPs; -930A/G, A640G and C242T) of the p22(phox) subunit have been associated with hypertension; however, their role in peripheral and central pressures in normotensive individuals has not been addressed. A total of 210 healthy, normotensive individuals were studied. Genotypes for the -930A/G, A640G and C242T polymorphisms were determined by polymerase chain reaction. Peripheral pressures were measured by mercury sphygmomanometer and aortic pressures by a validated device using applanation tonometry. Both peripheral and central pressures differed across -930A/G genotypes. G allele carriers showed higher levels of peripheral systolic blood pressure (PSBP; AA: 113+/-12, GG/AG: 119+/-12 mm Hg; P<0.01) and peripheral diastolic blood pressure (AA: 70+/-9, GG/AG: 73+/-10 mm Hg; P<0.05). Regarding central pressures, AA homozygotes had lower central systolic blood pressure (CSBP; AA: 103+/-12, GG/AG: 108+/-12 mm Hg; P<0.01) and central diastolic blood pressure (AA: 71+/-9, GG/AG: 74+/-10 mm Hg; P<0.05). In multiple linear regression analysis, presence of the G allele (AG or GG) independently predicted CSBP. Blood pressure levels did not differ across A640G and C242T genotypes. The -930A/G polymorphism of p22(phox) is a determinant of peripheral and central pressures in normotensive individuals. The G allele is associated with higher blood pressure in the brachial artery, as well as in the aorta. These findings further elucidate the role of this polymorphism in the regulation of blood pressure. In contrast, the A640G and C242T SNPs do not influence peripheral and central pressures in normotensives.

Arterial stiffness and wave reflections in marathon runners.

BACKGROUND: Regular aerobic exercise has beneficial effects on the cardiovascular system. Marathon running is an aerobic and extremely vigorous exercise. Arterial stiffness and wave reflections are independent predictors of cardiovascular risk. We investigated the acute effect of marathon race on aortic stiffness and wave reflections, as well as possible chronic alterations of these indexes in marathon runners. METHODS: We studied 49 marathon runners (age 38 +/- 9 years) and 46 recreationally active control subjects (age 37 +/- 5 years). To investigate the acute effect of marathon race, a subgroup of 20 runners was evaluated after the race as well. Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV) and wave reflections with augmentation index (AIx). RESULTS: Marathon runners had significantly higher systolic, diastolic, pulse (both aortic and brachial), and mean pressures compared to controls (P < 0.05 for all). Marathon runners had significantly higher PWV (6.89 m/s vs. 6.33 m/s, P < 0.01), whereas there was no difference in AIx and AIx corrected for heart rate (AIx@75) compared to controls (13.8% vs. 13.9%, P = 0.985 and 8.2% vs. 10.3%, P = 0.340, respectively). Marathon race caused a significant fall in both AIx (12.2% vs. -5.8%, P < 0.001) and AIx@75 (7.0% vs. 0.0%, P = 0.01), whereas PWV did not change significantly (6.66 m/s vs. 6.74 m/s, P = 0.690). Aortic and brachial systolic, diastolic, and mean pressures were also decreased (P < 0.05). CONCLUSIONS: A significant fall in wave reflections was observed after marathon race, whereas aortic stiffness was not altered. Moreover, marathon runners have increased aortic stiffness and pressures, whereas wave reflections indexes do not differ compared to controls.

Amino-terminal pro-C-type natriuretic peptide is associated with arterial stiffness, endothelial function and early atherosclerosis.

OBJECTIVE: C-type natriuretic peptide (CNP) is a paracrine molecule with effects on endothelial integrity, vascular tone and atherosclerotic process. Arterial stiffness, wave reflections, endothelial dysfunction and carotid intima-media thickness (IMT) are predictors of cardiovascular events. We investigated whether CNP is related to arterial structure and function in men. METHODS: We evaluated arterial structural and functional characteristics in 117 consecutive men (mean age 57.3 + or - 9.2 years), with and without cardiovascular risk factors, who had no established cardiovascular disease. Arterial elastic properties were evaluated with carotid-femoral pulse wave velocity (PWV), wave reflections with augmentation index (AIx), endothelial function with flow-mediated dilatation of the brachial artery (FMD) and early atherosclerosis with carotid IMT. Amino-terminal proCNP (NT-proCNP) was assessed in venous blood. RESULTS: The number of cardiovascular risk factors was inversely related to levels of NT-proCNP (P<0.01) and there was a progressive increase in Framingham risk score according to decreasing tertiles of NT-proCNP (P<0.001). In multivariable regression analysis NT-proCNP exhibited significant negative associations with PWV and IMT and positive association with FMD (all P<0.05) that were independent of age, blood pressure, smoking habits, body mass index, blood glucose, total triglycerides, low-density lipoprotein and endothelin-1 or high-sensitivity C-reactive protein. There was no relation between NT-proCNP and AIx. CONCLUSION: The present study is the first to demonstrate in a global arterial approach relationship between CNP and functional and early structural arterial changes. These findings elucidate pathophysiological links and may have important clinical implications for the estimation of cardiovascular risk in men.

Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis.

AIMS: To calculate robust quantitative estimates on the predictive value of central pressures and derived central haemodynamic indices for cardiovascular (CV) outcomes and all-cause mortality by meta-analysis of longitudinal studies. METHODS AND RESULTS: We meta-analysed 11 longitudinal studies that had employed measures of central haemodynamics and had followed 5648 subjects for a mean follow-up of 45 months. The age- and risk-factor-adjusted pooled relative risk (RR) of total CV events was 1.088 (95% CI 1.040-1.139) for a 10 mmHg increase of central systolic pressure, 1.137 (95% CI 1.063-1.215) for a 10 mmHg increase of central pulse pressure (PP), and 1.318 (95% CI 1.093-1.588) for a 10% absolute increase of central augmentation index (AIx). Furthermore, we found that a 10% increase of central AIx was associated with a RR of 1.384 (95% CI 1.192-1.606) for all-cause mortality. When compared with brachial PP, central PP was associated with marginally but not significantly higher RR of clinical events (P = 0.057). CONCLUSION: Central haemodynamic indexes are independent predictors of future CV events and all-cause mortality. Augmentation index predicts clinical events independently of peripheral pressures, while central PP has a marginally but not significantly (P = 0.057) better predictive ability when compared with peripheral PP.

Association of interleukin-18 levels with global arterial function and early structural changes in men without cardiovascular disease.

BACKGROUND: Increased levels of interleukin-18 (IL-18) have been related to plaque progression and vulnerability and cardiovascular outcomes. Arterial functional and structural characteristics and endothelial/inflammatory activation are important determinants of cardiovascular performance and predictors of risk. We investigated whether IL-18 is a determinant of global arterial function and early structural changes in men. METHODS: We evaluated arterial structural and functional characteristics (carotid-femoral pulse wave velocity (PWV), central aortic pressures, wave reflection indexes, flow-mediated dilation of the brachial artery, and common carotid intima-media thickness (IMT)) and we measured systemic inflammatory markers in 97 men (mean age 57.8 +/- 8.6 years) without manifest cardiovascular/atherosclerotic disease. RESULTS: Multivariable analysis adjusting for age, mean pressure, other risk factors, high-sensitivity C-reactive protein (hsCRP), and treatment showed independent associations between IL-18 level and carotid-femoral PWV (P < 0.01) and IMT (P = 0.03). On the other hand, no relationship between IL-18 and flow-mediated dilation, central pressures or augmentation index (AIx) was found. The combination of higher IL-18 level with higher carotid-femoral PWV and carotid IMT values showed greater effect on 10-year risk of a cardiovascular event. CONCLUSIONS: IL-18 level is independently associated with aortic stiffening and carotid early atherosclerosis. This finding underlines the important role of IL-18 as a marker of arterial damage, and implies a contribution of this compound to the pathophysiology of cardiovascular disease.

Divergent effects of laughter and mental stress on arterial stiffness and central hemodynamics.

OBJECTIVE: To investigate the effect of laughter and mental stress on arterial stiffness and central hemodynamics. Arterial stiffness and wave reflections are independent predictors of cardiovascular risk. Chronic psychological stress is an independent risk factor for cardiovascular events, whereas acute stress deteriorates vascular function. METHODS: Eighteen healthy individuals were studied on three occasions, according to a randomized, single-blind, crossover, sham procedure-controlled design. The effects of viewing a 30-minute segment of two films inducing laughter or stress were assessed. Carotid-femoral pulse wave velocity was used as an index of arterial stiffness; augmentation index was used as a measure of wave reflections. RESULTS: Laughter decreased pulse wave velocity (by 0.30 m/sec, p = .01), and augmentation index (by 2.72%, p = .05). Conversely, stress increased pulse wave velocity (by 0.29 m/sec, p = .05) and augmentation index (by 5.1%, p = .005). Laughter decreased cortisol levels by 1.67 microg/dl (p = .02), soluble P-selectin by 26 ng/ml (p = .02) and marginally von Willebrand factor (by 2.4%, p = .07) and increased total oxidative status (by 61 micromol/L, p < .001). Stress decreased interleukin-6 (by 0.11 pg/ml, p = .04) and increased total oxidative status (by 44 micromol/L, p = .007). Soluble CD40 ligand and fibrinogen remained unchanged. CONCLUSIONS: Positive (laughter) and negative (stress) behavioral interventions have divergent acute effects on arterial stiffness and wave reflections. These findings have important clinical implications extending the spectrum of lifestyle modifications that can ameliorate arterial function.

Amino-terminal pro-C-type natriuretic peptide is associated with the presence, severity, and duration of vasculogenic erectile dysfunction.

BACKGROUND: Endothelial dysfunction is a key event in the pathophysiology of erectile dysfunction (ED) and generalized vascular disease. C-type natriuretic peptide (CNP) is a paracrine molecule that effects endothelial integrity and vascular tone. OBJECTIVE: To determine the role of CNP in men with vasculogenic ED. DESIGN, SETTING, AND PARTICIPANTS: Fifty-two consecutive men (age: 57+/-10 yr) with nonpsychogenic and nonhormonal ED for >6 mo and free of cardiovascular disease who were referred to the Cardiovascular Diseases and Sexual Health Unit of our Department for evaluation of ED were compared with 31 subjects with normal erectile function matched for age, body mass index, and traditional risk factors. MEASUREMENTS: Vasculogenic ED was diagnosed according to comprehensive history, physical examination, Sexual Health Inventory for Men (SHIM-5) scoring, hormonal testing, and penile color-Doppler ultrasound. Amino-terminal proCNP (NT-proCNP) was measured in plasma with enzyme-linked immunosorbent assay (ELISA). RESULTS AND LIMITATIONS: Compared to controls, ED patients had significantly lower NT-proCNP levels (0.21+/-0.08 pmol/l in ED patients vs 0.34+/-0.07 pmol/l in control subjects; p<0.001). NT-proCNP levels were associated with erectile performance as expressed by SHIM-5 score (r=0.57; p<0.001), even after adjusting for confounders. There was also an inverse linear relationship between ED duration and NT-proCNP levels (p<0.05). In patients with arteriogenic ED, there was a positive correlation of NT-proCNP levels with peak systolic velocity (PSV) (r=0.51; p=0.01). CONCLUSIONS: CNP levels are associated with the presence, severity, and duration of ED. These findings provide further insight into the role of CNP in the pathophysiology of ED.