Mutual Effect Modification between Insulin Resistance and Endothelial Dysfunction in Predicting Incident Heart Failure in Hypertensives.

Insulin resistance and endothelial dysfunction are associated with heart failure (HF). Our objective was to investigate whether endothelial dysfunction and insulin resistance are independent predictors of incident HF and if a possible interaction exists between them. We enrolled 705 white never-treated hypertensives. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine. During the follow-up [median: 117 months (range: 31-211)], we documented 223 new cases of HF (3.3 events/100 patient-years). We stratified the study population into progressors and non-progressors; progressors showed an older age and a higher prevalence of females, as well as higher mean values of baseline glucose, insulin, homeostasis model assessment (HOMA), creatinine, and high-sensitivity C-reactive protein (hs-CRP), whereas the estimated glomerular filtration rate (e-GFR) and endothelium-dependent vasodilation were lower. In the multiple Cox regression analysis, serum hs-CRP (HR = 1.362, (95% CI = 1.208-1.536), HOMA (HR = 1.293, 95% CI = 1.142-1.465), maximal acetylcholine (Ach)-stimulated forearm blood flow (FBF) (100% increment, HR = 0.807, 95% CI = 0.697-0.934), and e-GFR (10 mL/min/1.73 m2 increment, HR = 0.552, 95% CI = 0.483-0.603) maintained an independent association with incident HF. HOMA and endothelial dysfunction interact between them in a competitive manner (HR = 6.548, 95% CI = 4.034-10.629), also showing a mutual effect modification. Our findings demonstrate that both endothelial dysfunction and HOMA are independent and strong predictors of incident HF in hypertensives, these two risk factors interact between them with a competitive mechanism.

Competitive interaction between smoking and chronic obstructive pulmonary disease for explaining renal function reduction in hypertensive patients.

Chronic kidney disease is a risk factor for cardiovascular events. Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for renal impairment. The aim of this study was to test the combined effect of smoking and COPD on renal function decline in hypertensives. We enrolled 1728 hypertensives stratified by smoking status and presence/absence of COPD. To test the mutual effect modification by both smoking and COPD and e-GFR, we performed crude and adjusted linear regression analyses, these latter taking into account potential confounders. Smokers displayed significantly lower e-GFR values than non-smokers (90 ± 24 vs. 121 ± 35 ml/min/1.73 m2); this difference was confirmed when comparing e-GFR values between patients with/without COPD (81 ± 17 vs. 109 ± 32 ml/min/1.73 m2). Smoking and COPD were directly and significantly interrelated (Cramer's V coefficient = 0.200; P = < 0.001). At interaction analyses, smoking significantly modified the effect of COPD on e-GFR and COPD significantly modified the effect of smoking on e-GFR, indicating a competitive interaction between smoking and COPD in the appearance of renal damage. e-GFR was 35 ml/min/1.73 m2 lower in patients with COPD than in those without; this reduction was of higher magnitude than that found between COPD and COPD-free patients among smokers (19 ml/min/1.73 m2). Smoking and COPD competitively interact in the appearance of renal function decline. These results suggest to screen for kidney damageboth smokers and COPD patients, especially those with both conditions.

Impact of Sacubitril/Valsartan on Clinical and Echocardiographic Parameters in Heart Failure Patients With Reduced Ejection Fraction: Data From a Real Life 2-year Follow-Up Study.

Heart failure (HF) represents a widespread health problem characterized by high morbidity and mortality. Sacubitril/Valsartan (sac/val) has improved clinical prognosis in patients affected by HF with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the effectiveness and durability of sac/val treatment on the clinical, hemodynamic and echocardiographic parameters, in real-life consecutive HFrEF outpatients, evaluated up to 2-years of follow-up. We collected 300 repeated observations over time in 60 patients suffering of HFrEF and symptomatic despite optimal drug therapy. Patients with left ventricular ejection fraction (LVEF) <35 and II-III NYHA functional class were considered. All patients underwent to clinical-instrumental and laboratory determinations and Minnesota Living with HF Questionnaire (MLHFQ) every 6 months until 24 months to evaluate possible clinical benefits and adverse events. During a 2-year follow-up period and through a 6-monthly control of the study variables both clinical, hemodynamic, biochemical and echocardiographic parameters significantly improved, in particular cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS). Furthermore, there was a reduction of NT-proBNP levels and betterment of renal function and NYHA functional class, demonstrating the efficacy and durability of sac/val treatment. In a multiple linear mixed model the longitudinal evolutions of CI were associated to concomitant changes of GLS and E/e' ratio. Our study, contemplating the collection of 300 repeated observations in 60 patients, provides a complete and detailed demonstration of sac/val effects, showing effectiveness, safety and effect durability of the treatment every 6 months up to 2-years of follow-up with significant improvement of several clinical, hemodynamic and echocardiographic parameters in HFrEF outpatients.

Association Between Sleep Apnea and Valvular Heart Diseases.

Background: Although sleep respiratory disorders are known as a relevant source of cardiovascular risk, there is a substantial lack of trials aimed to evaluate the eventual occurrence of associations between sleep apnea (SA) and valvular heart diseases (VHD). Methods: We recruited 411 patients referring to our sleep disorder unit, among which 371 had SA. Ninety-three subjects with SA also suffered from VHD. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient. Patient subgroups were comparatively evaluated through cross-sectional analysis. Results: A statistically significant increase in the prevalence of VHD was detected in relation to high apnea hypopnea index (AHI) values (p = 0.011). Obstructive sleep apnea occurrence was higher in SA patients without VHD (p < 0.0001). Conversely, central and mixed sleep apneas were more frequent among SA patients with VHD (p = 0.0003 and p = 0.002, respectively). We observed a direct correlation between AHI and BMI values (p < 0.0001), as well as between AHI and serum uric acid levels (p < 0.0001), high sensitivity C-reactive protein (p < 0.0001), and indexed left ventricular end-diastolic volume (p < 0.015), respectively. BMI and VHD resulted to be the main predictors of AHI values (p < 0.0001). Conclusions: Our study suggests that a significant association can occur between SA and VHD. It is clinically relevant that when compared to SA patients without VHD, higher frequencies of central and mixed apneas were found in subjects with SA and VHD. Moreover, after elevated BMI, VHD represented the second predictor of AHI values.

Uric Acid and Vascular Damage in Essential Hypertension: Role of Insulin Resistance.

Increased levels of uric acid (UA) have been shown to be correlated with many clinical conditions. Uric acid may adversely affect the insulin signalling pathway inducing insulin resistance (IR). Several studies report the association between arterial stiffness (AS), an early indicator of atherosclerosis, and UA. The purpose of the present study was to evaluate the association between UA and AS, considering the potential role of IR. We enrolled 1114 newly diagnosed, never-treated hypertensive patients. Insulin resistance was assessed by the homeostatic model assessment (HOMA) index. Arterial stiffness was evaluated as the measurement of the carotid-femoral pulse wave velocity (PWV). The study cohort was divided into subgroups, according to increasing tertiles of UA. The mean values of UA were 5.2 ± 1.6 mg/dL in the overall population. Pulse wave velocity was linearly correlated with UA (p < 0.0001), HOMA (p < 0.0001), high sensitivity C-reactive protein (p < 0.0001), systolic blood pressure (p < 0.0001) and LDL cholesterol (p = 0.005). Uric acid was the strongest predictor of PWV and was associated with the highest risk for increased AS. The interaction analysis showed that the joint effect of increased UA and HOMA was significantly higher than that expected in the absence of interaction under the additive model, indicating that the two biomarkers synergically interacted for promoting vascular damage. Our data showed that UA interacted with IR to increase AS in a large cohort of newly diagnosed, never-treated hypertensive patients.