COPD significantly increases cerebral and cardiovascular events in hypertensives

Essential hypertension and chronic obstructive pulmonary disease often coexist in the same patient. The aim of this study was to evaluate whether the addition of chronic obstructive pulmonary disease modifies the risk of cardiovascular events in hypertensives. We enrolled 1728 hypertensives. Study outcomes included fatal and non-fatal cardiovascular stroke and myocardial infarction, and cardiovascular death. During a mean follow-up of 57 months there were 205 major adverse cardiovascular events (2.47 per 100 pts/yr): cardiac (n117; 1.41 per 100 pts/yr) and cerebrovascular (n = 77; 0.93 per 100 pts/yr). In hypertensives with chronic obstructive pulmonary disease we observed a greater number of cardiovascular events than in hypertensives without respiratory disease (133 [5.55 per 100 pts/yr) vs 72 [1.22 per 100 pts/yr], respectively. The addition of chronic obstructive pulmonary disease to hypertension increased the incidence of total and non-fatal stroke of more than nine- (2.42 vs 0.32 per 100 pts/yr) and 11-fold (2.09 vs 0.22 per 100 pts/yr), respectively. The same trend was observed for total (2.88 vs 0.81 per 100 pts/yr) and non-fatal (2.67 vs 0.79 per 100 pts/y) myocardial infarction. The presence of chronic obstructive pulmonary disease in hypertensives significantly increases the risk of stroke, myocardial infarction and major adverse cardiovascular events

Asymmetric Dimethylarginine, L-Arginine, and Endothelial Dysfunction in Essential Hypertension

ObjectivesWe investigated the relationship between ADMA plasma levels and endothelium-dependent vasodilation in 36 never-treated essential hypertensives and in 8 normotensive healthy subjects.BackgroundIt has been demonstrated that endothelium-dependent vasodilatation is impaired in essential hypertension. The potential contribution of asymmetric dimethylarginine (ADMA) to endothelial dysfunction of hypertensive humans has received poor attention.MethodsEndothelial function was measured during intra-arterial infusion of acetylcholine (ACh), alone and during co-infusion of L-arginine, and sodium nitroprusside at increasing doses. Concentrations of ADMA and L-arginine in plasma were measured by high-performance liquid chromatography.ResultsHypertensive subjects had significantly higher ADMA and L-arginine plasma concentrations than normotensive healthy controls; ACh-stimulated forearm blood flow (FBF) was significantly reduced in hypertensive subjects in comparison to normotensive control subjects (p < 0.0001). Intra-arterial coinfusion of L-arginine induced a further significant enhancement in ACh-stimulated vasodilation in hypertensive patients. In these, ADMA was strongly and inversely associated with the peak increase in FBF. In a multivariate model, only ADMA and L-arginine were independent correlates, accounting for 33.9% and 8.9% of the variability in the peak FBF response to ACh (p < 0.0001), respectively.ConclusionsThe main finding in this study is that in essential hypertensives the L-arginine and endogenous inhibitor of nitric oxide synthase, ADMA, are inversely related to endothelial function

Alkaline phosphatase affects renal function in never-treated hypertensive patients. effect modification by age

Several studies in patients with chronic kidney disease or normal renal function have shown that high levels of tissue non-specific alkaline phosphatase (ALP) are associated with an increased risk of all cause and cardiovascular (CV) mortality. Considering the independent prognostic role of renal function, we investigated the possible association between ALP levels and estimated glomerular filtration rate (e-GFR) in a large cohort of hypertensive subjects. We enrolled 2157 never-treated uncomplicated hypertensive patients with ALP levels within normal range. In the whole population, e-GFR was strongly related to ALP (r = -0.43, P &lt; 0.0001) with similar magnitude in females and in males, resulting ALP the second independent predictor of renal function. In a multiple linear regression model, both on crude (P &lt; 0.001) and adjusted (P = 0.01) analyses age significantly modified the effect of a fixed increase in ALP (20 UI/L) on renal function so that the reduction in e-GFR associated to a 20 UI/L increase in ALP was of lower magnitude in younger patients and progressively of higher extent from 20 years of age onwards. In conclusion, present data indicate a significant relationship between ALP levels and e-GFR in uncomplicated hypertensive patients that is modulated by age and that persisted after adjusting for several confounders

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Endothelial Function and Dipper Status

SUMMARY Aims: Essential hypertension, as well as other established cardiovascular risk factors, is associated with endothelial dysfunction. Hypertensive patients with a nondipper circadian pattern have a greater risk of cerebrovascular and cardiovascular complications in comparison with those with a dipper circadian pattern. In this study, we evaluated the association between nondipper pattern and endothelial function in patients with essential hypertension. Methods: We evaluated the forearm blood flow (FBF) response to intraarterial acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, infusions in 190 hypertensive patients stratified according to dipper and nondipper status. The FBF was measured by strain-gauge plethysmography. Effects of oxidative stress on FBF were evaluated by intraarterial infusion of vitamin C. Ambulatory BP monitorings were obtained by a validated oscillometric device (SpaceLabs 90207 Monitor Inc., Issaquah, WA, USA). Results: Systolic and diastolic blood pressures were higher during daytime and lower during night-time in dipper subjects than in nondippers. The peak percent increase in ACh-stimulated FBF was higher in dippers than in nondippers (473% vs. 228%, P < 0.001). The FBF responses to SNP were similar in dipper and nondipper patients. The FBF response to ACh during coinfusion of vitamin C was higher in nondippers rather than in dipper hypertensives. Conclusions: Present data demonstrate that endothelium-dependent vasodilation is impaired in patients who have nondipper hypertension. The effects of vitamin C on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction of nondipper hypertensive patients

Insulin-resistance HCV infection-related affects vascular stiffness in normotensives

Background and Aims. Arterial stiffness evaluated as pulse wave velocity, is an early marker of vascular damage and an independent predictor for cardiovascular events. We investigated if the insulin resistance/hyperinsulinemia chronic hepatitis C virus infection-related could influence arterial stiffness. Methods. We enrolled 260 outpatients matched for age, body mass index, gender, ethnicity: 52 with never-treated uncomplicated chronic hepatitis C virus infection (HCV+), 104 never-treated hypertensives (HT) and 104 healthy subjects (NT). Pulse wave velocity was evaluated by a validated system employing high-fidelity applanation tonometry. We also measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, e-GFR-EPI, HOMA, quantitative HCV-RNA. Results. HCV+ patients with respect to NT had an increased pulse wave velocity (7.9 ± 2.1 vs 6.4 ± 2.1 m/s; P &lt; 0.0001), similar to that observed in HT group (8.8 ± 3.2 m/s). HCV+ patients, in comparison with NT, had higher triglyceride, creatinine, fasting insulin and HOMA (3.2 ± 1.3 vs 2.5 ± 1.0; P &lt; 0.0001). At linear regression analysis, the correlation between pulse wave velocity and HOMA was similar in HT (r = 0.380, P &lt; 0.0001) and HCV+ (r = 0.369, P = 0.004) groups. At multiple regression analysis, HOMA resulted the major determinant of pulse wave velocity in all groups, explaining respectively 11.8%, 14.4% and 13.6% of its variation in NT, HT and HCV+. At correlational analysis hepatitis C virus-RNA and HOMA demonstrated a strong and linear relationship between them, explaining the 72.4% of their variation (P = 0.022). Conclusions. We demonstrated a significant and direct correlation between HOMA and pulse wave velocity in HCV+ patients, similar to that observed in hypertensive

Continuous positive airway pressure improves renal function in obese patients with obstructive sleep apnea syndrome

Background: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular morbidity and mortality, and it has a detrimental effect on renal function. Obesity is the major risk factor for OSAS, and represents a risk factor for chronic kidney disease. Continuous positive airway pressure (CPAP) is the suggested therapy for moderate-to-severe OSAS. We designed this study to evaluate the effect of CPAP on estimated glomerular filtration rate (e-GFR) in a cohort of obese patients with moderate-to-severe OSAS and normal renal function. Methods: We enrolled 198 obese subjects, divided into two groups (OSAS+ and OSAS-), on the basis of cardiorespiratory monitoring; mild OSAS patients (n = 33) were excluded from the study, thus the analyses were conducted on 165 patients. Comparisons between groups were made by Student t-test or chi2 test as appropriate. Linear regression analyses were used to assess the relationship between baseline e-GFR and different covariates and, in the OSAS+ group, between Deltae-GFR and different covariates. A multivariate regression analysis was performed to determinate the independent predictor of the Deltae-GFR. Results: OSAS+ subjects showed significantly increased values of systolic blood pressure, HOMA, pulse wave velocity, high-sensitivity C reactive protein and uric acid compared with OSAS- group. OSAS+ group showed significantly lower values of e-GFR and increased values of microalbuminuria. At linear regression analysis e-GFR resulted significantly and inversely related to AHI in the whole study population and in the two groups. After 6 months of CPAP therapy, OSAS+ subjects showed an improvement in respiratory parameters, as well as a significant increase in e-GFR values (104.2 + 19.0 vs. 84.0 + 13.1 ml/min/1.73 m2, P &lt; 0.0001). At multiple regression analysis, Delta apnea/hypopnea index (AHIa) resulted the main independent predictor of Deltae-GFR explaining 22% of its variation. Conclusions: Obese OSAS patients show significantly lower values of e-GFR, even if in the normal range, compared with obese non-OSAS subjects. After 6 months of CPAP, e-GFR significantly improved (+20 ml/min/1.73 m2) and DeltaAHIa resulted the most important independent predictor of Deltae-GFR

Immunity, Inflammation and Heart Failure. Their Role on Cardiac Function and Iron Status

Aims: Heart failure is a clinical syndrome characterized by subclinical systemic inflammation and immune system activation associated with iron deficiency. No data exist on the various activations of immune-mediated mechanisms of inflammation in heart failure patients with reduced/preserved ejection fraction. We aimed to (1) investigate possible differences in inflammatory parameters and oxidative stress, and (2) detect a different iron status between groups. Materials and Methods: We enrolled 50 consecutive Caucasian outpatients with heart failure. All patients underwent echocardiographic measurements, laboratory determinations, evaluation of iron status and Toll-like receptors, and NF-κB expression in peripheral blood mononuclear cells, as well as pro-inflammatory cytokines. All statistical calculations were made using SPSS for Mac version 21.0. Results: Patients with reduced ejection fraction showed significantly lower hemoglobin levels (12.3 ± 1.4 vs. 13.6 ± 1.4 g/dl), serum iron (61.4 ± 18.3 vs. 93.7 ± 33.7 mcg/dl), transferrin iron binding capacity (20.7 ± 8.4 vs. 31.1 ± 15.6 %), and e-GFR values (78.1 ± 36.1 vs. 118.1 ± 33.9 ml/min/1.73 m2) in comparison to patients with preserved ejection fraction, while unsaturated iron binding capacity (272.6 ± 74.9 vs. 221.7 ± 61.4 mcg/dl), hepcidin (4.61 ± 0.89 vs. 3.28 ± 0.69 ng/ml), and creatinine (1.34 ± 0.55 vs. 1.03 ± 0.25 mg/dl) were significantly higher in the same group. When considering inflammatory parameters, patients with reduced ejection fraction showed significantly higher expression of both Toll-like receptors-2 (1.90 ± 0.97 vs. 1.25 ± 0.76 MFI) and Toll-like receptors-4 (4.54 ± 1.32 vs. 3.38 ± 1.62 MFI), respectively, as well as a significantly higher activity of NF-κB (2.67 ± 0.60 vs. 1.07 ± 0.30). Furthermore, pro-inflammatory cytokines, interleukin-1, and interleukin-6, was significantly higher in patients with reduced ejection fraction, while the protective cytokine interleukin-10 was significantly lower in the same group. Correlational analyses demonstrated a significant and inverse relationship between left ventricular function and inflammatory parameters in patients with reduced ejection fraction, as well as a direct correlation between ferritin and inflammatory parameters. Conclusions: Our data demonstrate a different immune-mediated inflammatory burden in heart failure patients with reduced or preserved ejection fraction, as well as significant differences in iron status. These data contribute to further elucidate pathophysiologic mechanisms leading to cardiac dysfunction

One hour-post-load plasma glucose ≥155 mg/dl in healthy glucose normotolerant subjects is associated with subcortical brain MRI alterations and impaired cognition. A pilot study

Background: Glucose alterations are associated with impaired cognition. The 1-h-post-load plasma glucose ≥155mg/dl in non-diabetic subjects confers an increased risk of cardiovascular events and diabetes. This pilot study aimed to investigate whether the 1-h-post-load plasma glucose ≥155 mg/dl negatively affects the subcortical regions of the brain and the cognitive functions. Methods: We enrolled 32 non-diabetic subjects. Patients were divided into two groups based on 1-h- post-load plasma glucose value &gt; or &lt; 155 mg/dl: normal glucose tolerance (NGT) 1-h-high and NGT 1-h-low subjects. All subjects underwent 3 Tesla MRI and standard neuropsychological tests. Results: NGT 1-h-high subjects showed significantly lower values of both right (4.9 ± 0.9 vs. 5.1 ± 0.9ml) and left (4.8 ± 1.1 vs. 5.1 ± 1.1ml) hippocampal hemisphere volume, while right hemisphere hippocampal diffusivity was lower in the NGT 1-h-high group (10.0 ± 0.6 vs. 10.6 ± 0.5 10−4 mm2s−1). NGT 1-h-high subjects also showed a poorer memory performance. In particular, for both Rey Auditory Verbal Learning Task (RAVLT)—immediate-recall and Free and Cued Selective Reminding Test (FCSRT)—delayed total recall, we found lower cognitive test scores in the NGT-1 h-high group (26.5 ± 6.3 and 10.4 ± 0.3, respectively). Conclusions: One-hour-post-load hyperglycemia is associated with morpho-functional subcortical brain alterations and poor memory performance tests