Chronic kidney disease (CKD) is associated with worse prognosis in acute coronary syndromes (ACS).We sought to investigate the prognostic effect of conservative management of ACS in CKD patients in a tertiary University Hospital.Two hundred and one patients (mean age 66.5 ± 13.6 years, 150 males) admitted to our Hospital with ACS from 2016-2017 were included in the study. CKD was defined by an estimated glomerular filtration rate (eGFR) < 60 ml/min/m2, as assessed by the Modification of Diet in Renal Disease (MDRD) equation. We grouped patients into four groups according to their CKD status and whether they underwent coronary angiography or not. Patients were followed for a median of 2 years post the index event. The primary outcome was all-cause death and secondary outcomes were cardiovascular and non-cardiovascular death.The majority of patients (n = 120, 60%) presented with non-ST elevation ACS (NSTE-ACS), whereas 81 patients as ST-elevation myocardial infarction (STEMI) (40%). 135 patients (68%) had history of hypertension. Fifty-four patients (27%) were identified as CKD patients. Overall, 29 patients (14.4%) did not undergo coronary angiography. Patients at a higher age and with CKD were more likely to not undergo angiography. Thirty-seven (18.4%) died during follow-up (25 non-cardiovascular deaths and 12 cardiovascular deaths). Patients with conservative treatment and CKD had the worse prognosis (Hazard ratio [HR] = 11.00, 95% Confidence intervals [CI] 4.00 to 30.24, p < 0.001) followed by non-CKD patients with conservative treatment (HR = 4.37, 95% CI 1.20 to 15.90, p = 0.025) compared to non-CKD patients treated invasively (reference group) after adjusting for age, gender, STEMI/NSTE-ACS diagnosis. Results were similar for non-cardiovascular death, whereas regarding cardiovascular death only the group with CKD and conservative treatment had a lower survival compared to the reference group (HR = 26.5, 95% CI 2.9 to 241.7, p = 0.004).Patients with ACS and CKD have higher mortality from both cardiovascular and non-cardiovascular causes than patients without CKD. Regardless of CKD status, conservative management of ACS was associated with higher long-term mortality versus invasive management in all patients.
Objective: Kidney dysfunction, defined either as estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 or as the presence of microalbuminuria, is associated with adverse cardiovascular events in hypertensive patients. Metabolic syndrome (MS) is a cluster of cardiometabolic abnormalities and conveys a high cardiovascular risk. Insulin resistance constitutes the main underlying pathophysiological mechanism of MS. Whether it is insulin resistance or hyperglycemia per se that has the greater effect on kidney function in patients with MS, is not thoroughly investigated. Design and method: We studied 526 never treated hypertensive patients with MS, defined by ATP III criteria, free from overt cardiovascular disease. Kidney function was estimated in all patients by calculating eGFR using the MDRD formula. Urine albumin concentration was measured after 24 h urine collection and albumin-to-creatinine ratio (ACR) was calculated. Insulin resistance was assessed by applying the homeostasis model assessment (HOMA-IR). Glycated hemoglobin A1c (HbA1c) was measured in all participants. Results: Mean values of HbA1c and HOMA-IR were 5.9% and 3.4, respectively. In univariate analysis, eGFR was related to age, male gender, smoking, total cholesterol, hsCRP, fasting glucose, HbA1c (r = −0.23, p < 0.001) and HOMA-IR (r = −0.09, p = 0.04). Accordingly, ACR was related to age, smoking, BMI, waist-to-hip ratio, mean arterial pressure, hsCRP, fasting glucose, HbA1c (r = 0.37, p < 0.001) and HOMA-IR (r = 0.22, p < 0.001). In linear regression analysis, after adjustment for several confounders, an independent association was demonstrated between eGFR and HbA1c (b = −0.38, p = 0.04), whereas the association of eGFR with HOMA-IR became non significant (b = −0.02, p = NS). Similar pattern was also evident for ACR since a strong association with HbA1c (b = 0.58, p = 0.001) was established, whereas no relationship between ACR and HOMA-IR was observed (b = 0.06, p = NS). Conclusions: In hypertensive patients with MS, HbA1c is a strong determinant of kidney function independently of insulin resistance or other components of MS. It might be suggested that the impaired kidney function and microalbuminuria, associated with abnormal glucose regulation, may mediate part of the increased cardiovascular risk related to MS. Thus, measurement of HbA1c may add in risk stratification and may serve as a treatment target in hypertensive patients with MS.
Abstract Introduction Malignancies are the second leading cause of death worldwide. Treatment Monoclonal Antibody (MAbs)-based treatment of cancer has been established as one of the most successful therapeutic strategies in the last 20 years; however, there is a growing concern about the effects of these agents on patients’ cardiovascular profile. Areas Covered In this manuscript we summarize current evidence regarding MAb effects on arterial stiffness, which is an recognised biomarker of cardiovascular risk. For this purpose, we explored two bibliographic databases [PubMed, Scopus] and one full-text database (Google-Scholar) for all publications published on MAbs’ effects on arterial stiffness until December 2019. Only few of the monoclonal antibody agents used in oncology have been investigated as per their effects on arterial properties and this limited evidence suggests that cancer therapy with monoclonal antibodies demonstrates either a temporary or long-term increase in arterial stiffness. Discussion It seems that by targeting ‘checkpoints’ in cancer genesis, anticancer MAbs also affects vascular properties causing endothelial dysfunction and arterial stiffness. Furthermore, several MAbs cause hypertension and may as a result increase pulse wave velocity. On the other hand, MAbs that target inflammatory cytokines seem to improve cardiovascular survival however, their effect on arterial stiffness is yet to be investigated. Further research is warranted in order to elucidate the biochemical pathways, clinical implications and potential reversibility of monoclonal antibody chemotherapy-induced vascular dysfunction.
Abstract Background/Introduction Regular aerobic exercise has beneficial effects on the cardiovascular system. Marathon running is an aerobic and extremely vigorous exercise. Endothelial function and carotid subclinical atherosclerosis are independent predictors of cardiovascular risk. Purpose We investigated the chronic alterations of these indices in marathon runners. Methods We studied 30 marathon runners and 20 age- and sex-matched recreationally active control subjects. Endothelial function was evaluated with flow-mediated dilatation of the brachial artery (FMD) and early atherosclerosis with carotid intima-media thickness (cIMT). All subjects completed analytical questionnaires about their medical history and training. Results Marathon runners had significantly higher systolic and pulse pressure compared to controls. They also had reduced body-mass index, waist to hip ratio and heart rate compared to controls (p<0.05, for all). Common cIMT was significantly lower in athletes than controls (0.56±0.11 vs. 0.63±0.07, p=0.029), while there was no difference in carotid bulb IMT between groups. FMD was higher in marathon runners compared to controls and nitrate-mediated dilatation (NMD) was similar in the two groups (9.0±3.7 vs. 6.4±1.7 and 12.6±5.7 vs. 12.3±3.4; p=0.002 and p=0.821, respectively). We also observed a reverse U-shaped curve between endothelial function and amount of exercise. (Figure) Effect of amount of exercise on FMD Conclusions Our study shows, that marathon runners have higher FMD compared to controls, indicating better vascular endothelial function, and also have lower cIMT compared to controls. Increased amount of exercise training seems to abolish the beneficial effect of exercise on endothelial function. These findings provide further insights in the effects of marathon running on endothelial function and carotid atherosclerosis.
Abstract Purpose To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Methods Thirty-two participants (mean age 37±8 years, 20 men) that received the BNT162b2 mRNA COVID-19 vaccine were studied in 3 sessions in a sequence-randomized, sham-controlled, assessor-blinded, cross-over design. Primary outcome was endothelial function assessed by brachial artery flow-mediated dilatation (FMD), and secondary outcomes were aortic stiffness, evaluated with carotid-femoral pulse wave velocity (PWV), microvascular function that was estimated with hyperemic mean blood flow velocity (HMBFV) of the brachial artery, and inflammation measured by high-sensitivity C-reactive protein (hsCRP) and interleukins (hsIL-6 and hsIL-1b) in blood samples. The outcomes were assessed prior to, and at 8h, 24h post the 1st dose of vaccination, and 8h, 24h and 48h post the 2nd. Results There was an increase in hsCRP that was apparent at 24h after both the 1st dose (−0.60 [95% Confidence intervals [CI]: −1.60 to −0.20], p=0.013) and the 2nd dose (max median difference at 48h −6.60 [95% CI: −9.80 to −3.40], p<0.001) compared to sham. Similarly, interleukins also increased. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p=0.037) at 24h post the 2nd dose (Figure). FMD values returned towards baseline at 48h. HMBFV remained unchanged during the 1st dose but at 48h post the 2nd dose was numerically lower than the sham procedure but the difference between the 2 sessions was not statistically significant (max mean difference at 48h 8.6 [95% CI: −0.6 to 17.8], p=0.067). Conclusions Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose and a transient deterioration of endothelial function at 24h that returns towards baseline at 48h. These results confirm the short-term cardiovascular safety of the vaccine. Funding Acknowledgement Type of funding sources: None.
Abstract Purpose Hypercholesterolemia is common in hypertensive patients and its presence increases the risk of cardiovascular (CV) complications. Decreased concentration of testosterone appears commonly in men with hypertension, and is an independent predictor of CV events. We investigated the utility of testosterone concentration measurement as an aid in the risk prediction of CV events in men with arterial hypertension and high LDL levels. Methods A cohort of 321 men with arterial hypertension and without known diabetes or atherosclerotic CVD (mean age: 54±9 years) were followed for the occurrence of major adverse cardiovascular events (MACE), (CV death, coronary artery disease, stroke). Total testosterone (TT) and LDL levels were measured in all patients. We used Cox proportional hazards regression to analyze the associations between LDL, serum testosterone and CV outcomes. Results During a mean follow-up of 6 years (range: 1–11 years), 31 (9.5%) patients demonstrated a MACE. Patients in the CV-event group were older and they had higher LDL and lower baseline TT levels compared to subjects in the event-free survival group (all P<0.01) while BMI, systolic blood pressure and smoking exposure (pack-years) were similar. Based on the observed distribution of baseline LDL levels the study cohort was divided in two groups: low LDL (<130 mg/dl) and high LDL (≥130 mg/dl). According to baseline TT level distribution the study cohort was divided in two groups: normal TT (>4.0 ng/mL) and low TT (≤4.0 ng/mL). Subjects in the high LDL group, had no increased risk of MACE compared to subjects in the low LDL group (HR 1.35; 95% CI 0.75–2.04) in the multivariable model. Moreover, there was no statistically significant association between low TT and risk of MACE. HR for low TT vs high TT was 1.48 (95% CI 0.85–2.16). We then subdivided the two LDL (high vs low) groups into subgroups according to presence of low or normal TT. Cox regression analysis revealed that the subgroup of men with both low TT and high LDL had an almost 2-fold higher risk of MACEs compared to the other three LDL/TT subgroups (adjusted hazard ratio: 2.07; 95% CI 0.94–3.56, P=0.035). Figure 1 shows the cardiac event-free survival curve of males with both baseline low TT and high LDL level with that of males in the other three LDL/TT subgroups (log rank: 11.3, P=0.008). Conclusion Low testosterone concentration is associated with a shorter event-free period in hypertensive patients with higher LDL levels. The measurement of testosterone concentration may be useful to further stratify the risk of middle-aged men with arterial hypertension and hypercholesterolemia. Funding Acknowledgement Type of funding sources: None.
Objective: There is evidence for an inverse association between plasma testosterone and blood pressure. Recently, low plasma testosterone was associated with increased risk of major cardiovascular events in middle-aged hypertensive men. Central (aortic) blood pressures predict cardiovascular mortality with equal ability compared to peripheral (brachial) blood pressures. The aim of the present study was to assess the relationship of plasma total testosterone (TT) with peripheral and central haemodynamics in hypertensive men. Design and method: We studied 70 non-diabetic, hypertensive men (mean age = 60 years old). Office brachial systolic (bSBP) and diastolic (bDBP) blood pressures were measured according to the ESH guidelines. Pulse pressure (bPP) was calculated as SBP minus DBP. All patients were subject to measurement of aortic systolic (aoSBP), diastolic (aoDBP) and pulse pressures (aoPP) by pulse wave analysis using the Sphygmocor device. Wave reflections were assessed by the measurement of heart-rate corrected augmentation index (AIx75). Plasma TT was measured in all subjects by enzyme immunoassay. Results: The mean value of TT in the whole population was 4.6 ng/ml (hypogonadism was defined as TT < 3.4 ng/ml). Plasma TT was inversely and significantly related to aoSBP (r = -0.26, p = 0.03), aoPP (r = -0.30, p = 0.01) and AIx75 (r = -0.31, p = 0.01) but only marginally related to bSBP (r = -0.22, p = 0.07) and bPP (r = -0.23, p = 0.06). In linear regression analysis, after adjustment for age, smoking, BMI, plasma glucose, total cholesterol and presence of antihypertensive treatment, aoSBP (b = -0.29, p = 0.03), aoPP (b = -0.31, p = 0.02) and AIx75 (b = -0.30, p = 0.03) were independently associated with TT but the relationship of TT with bSBP (b = -0.25, p = 0.06) and bPP (b = -0.23, p = 0.07) remained weak. Conclusions: In hypertensive men, plasma TT is independently and inversely associated with central blood pressures and wave reflections. Considering the adverse prognostic role of central blood pressures on cardiovascular outcomes, the present finding might explain part of the increased cardiovascular risk associated with low testosterone. Whether measurement of central haemodynamics may improve risk stratification in men with low testosterone, warrants further investigation.
Abstract Background/Introduction The quantitative flow ratio (QFR) based functional Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (FSSQFR) takes into consideration not only the anatomy but also the physiology of coronary arteries. Purpose To investigate the prognostic value of the FSSQFR. Methods We performed an offline QFR analysis in consecutive patients who underwent coronary angiography in a single center. FSSQFR was counted by summing the individual scores only in ischemia-producing lesions (vessel QFR ≤0.8). Patients were divided into low-, intermediate- and high risk according to SS and FSS with the same cutoff. The primary endpoint was the estimation of the predictive value of FSSQFR for the composite outcome of death, myocardial infarction, ischemia-driven revascularization, stroke, hospitalization for heart failure, and life-threatening arrhythmias. Results 410 patients were included in this study. Baseline characteristics of the population displayed in Table 1. FSSQFR and SS were estimated for all patients. According to SS, 26.6% of patients were high risk, 36.6% were intermediate risk and 36.8% were low cardiovascular risk. After calculating FSSQFR, risk stratification changed in 10% of the study population, more specifically 21.2%, 36.6%, and 42.2% of patients were classified as high-, intermediate- and low-risk respectively. 5% (n=20) of the patients for whom coronary artery bypass grafting would be recommended according to SS, converted in favor of percutaneous coronary intervention after FSSQFR calculation. After a median 30.2 (25.7–33.7) months follow-up period multivariate regression analysis showed FSSQFR was an independent predictor of primary endpoint after adjustment for age, gender, BMI, and hypertension (adjusted OR: 1.03 [95% CI, 1.01–1.06]; P=0.012). The Kaplan-Meier estimate for the primary endpoint was 15%, 18.7%, and 32.2% in the low, intermediate, and high FSSQFR group, respectively (log-rank P=0.001; Figure 1A) and cardiac death was 2.3%, 8.7%, and 12.6% in the low, intermediate, and high FSSQFR group, respectively (log-rank P=0.003; Figure 1B). Conclusions In our study, FSSQFR showed discordance with classical anatomical SS leading to risk re-stratification of patients with coronary disease and possible alternative treatment strategy and also was found to be an independent predictor of higher cardiovascular adverse events. Funding Acknowledgement Type of funding sources: None.
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