Aggravated Dental and Periodontal Status in Patients with Sickle Cell Disease and Its Association with Serum Ferritin.

AIM: The present study aimed to evaluate the possible consequences of sickle cell disease (SCD) on dental and periodontal health in middle-aged patients and to examine the association of certain cardiovascular parameters and serum ferritin with the dental and periodontal status. MATERIALS AND METHODS: Thirty-seven patients (mean age 43.2 years old) with SCD and 30 non-SCD and otherwise healthy individuals (mean age 38.9 years old) were examined for caries experience and periodontal status in addition to cardiovascular characteristics and ferritin level in serum. RESULTS: Compared to controls, SCD patients exhibited higher plaque and gingival bleeding scores, higher prevalence of periodontal diseases, and higher caries experience. Multiple stepwise linear regression analysis showed that caries experience was predominantly determined by the presence of SCD and the age, while major determinants of periodontitis were the ferritin levels and the male gender. The results reveal an aggravation of oral health in SCD patients regarding both caries and periodontal diseases. CONCLUSION: A potential role of the increased central inflammatory response, reflected by the elevated ferritin level in serum, is suggested for the impaired periodontal health of SCD patients. CLINICAL SIGNIFICANCE: Compliance with precautionary dental checks and early management of dental complications is of great importance in order to improve oral health status and prevent general health complications in SCD patients.

Wave reflections and systemic vascular resistance are stronger determinants of pulse pressure amplification than aortic stiffness in drug-naïve hypertensives.

Background: Aortic-to-brachial pulse pressure (PP) amplification is a novel biomarker that prognosticates the cardiovascular risk above and beyond central aortic and brachial blood pressure. This phenomenon is modulated by left ventricular contractility and chronotrophy, large-artery stiffness and reflecting properties of microcirculation. However, the relative importance of these parameters as hemodynamic determinant of PP amplification remains elusive.Methods: A total of 88 consecutive drug-naïve hypertensives underwent a non-invasive assessment of central and peripheral hemodynamics via impedance cardiography and pulse wave analysis. Participants were classified into tertiles according to the magnitude of PP amplification. Hemodynamic determinants of low PP amplification were explored in univariate and multivariate regression analysis.Results: Compared with the high tertile, patients within the low PP amplification tertile were older and more commonly female and had lower height, weight and heart rate. Augmentation index (AIx) and systemic vascular resistance index (SVRI) were higher among patients within the low PP amplification tertile, whereas aortic pulse wave velocity (PWV) did not differ among groups. In multivariate analysis, higher AIx (OR: 1.27; 95% CI: 1.09-1.48) and higher SVRI were independently associated with higher odds for low PP amplification, whereas higher heart rate was the only parameter related to lower odds for low PP amplification (OR: 0.84; 95% CI: 0.71-0.99).Conclusion: This study shows that among newly-diagnosed drug-naïve hypertensives, elevated wave reflections and systemic vascular resistance are stronger determinants of PP amplification than aortic stiffness.

Stroke Incidence and Outcomes in Northeastern Greece: The Evros Stroke Registry.

BACKGROUND AND PURPOSE: Data are scarce on both stroke incidence rates and outcomes in Greece and in rural areas in particular. We performed a prospective population-based study evaluating the incidence of first-ever stroke in the Evros prefecture, a region of a total 147 947 residents located in North Eastern Greece. METHODS: Adult patients with first-ever stroke were registered during a 24-month period (2010-2012) and followed up for 12 months. To compare our stroke incidence with that observed in other studies, we standardized our incidence rate data according to the European Standard Population, World Health Organization, and Segi population. We also applied criteria of data quality proposed by the Monitoring Trends and Determinants in Cardiovascular Disease project. Stroke diagnosis and classification were performed using World Health Organization criteria on the basis of neuroimaging and autopsy data. RESULTS: We prospectively documented 703 stroke cases (mean age: 75±12 years; 52.8% men; ischemic stroke: 80.8%; intracerebral hemorrhage: 11.8%; subarachnoid hemorrhage: 4.4%; undefined: 3.0%) with a total follow-up time of 119 805 person-years. The unadjusted and European Standard Population-adjusted incidences of all strokes were 586.8 (95% confidence interval [CI], 543.4-630.2) and 534.1 (95% CI, 494.6-573.6) per 100 000 person-years, respectively. The unadjusted incidence rates for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were 474.1 (95% CI, 435-513), 69.3 (95% CI, 54-84), and 25.9 (95% CI, 17-35) per 100 000 person-years, respectively. The corresponding European Standard Population-adjusted incidence rates per 100 000 person-years were 425.9 (95% CI, 390.9-460.9), 63.3 (95% CI, 49.7-76.9), and 25.8 (95% CI, 16.7-34.9) for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, respectively. The overall 28-day case fatality rate was 21.3% (95% CI, 18.3%-24.4%) for all strokes and was higher in hemorrhagic strokes than ischemic stroke (40.4%, 95% CI, 31.3%-49.4% versus 16.2%, 95% CI, 13.2%-19.2%). CONCLUSIONS: This is the largest to date population-based study in Greece documenting one of the highest stroke incidences ever reported in South Europe, highlighting the need for efficient stroke prevention and treatment strategies in Northeastern Greece.

Accuracy of a Newly-Introduced Oscillometric Device for the Estimation of Arterial Stiffness Indices in Patients on Peritoneal Dialysis: A Preliminary Validation Study.

The aim of the present study was to compare the aortic systolic blood pressure (aSBP), heart-rate-adjusted augmentation index (AIx75), and pulse wave velocity (PWV) obtained using the Mobil-O-Graph (IEM, Stolberg, Germany) and SphygmoCor (AtCor, Sydney, Australia) devices in patients receiving peritoneal dialysis (PD).After a 10-minute rest in the supine position, the Mobil-O-Graph and SphygmoCor devices were applied in randomized order in 27 consecutive PD patients. The agreement between the measurements produced by the Mobil-O-Graph and SphygmoCor devices was explored using Bland-Altman analysis.The Mobil-O-Graph-derived aSBP, AIx75, and PWV did not differ from the same measurements obtained with SphygmoCor (aSBP: 120.5 ± 18.2 mmHg vs. 124.4 ± 19.0 mmHg, p = 0.438; AIx75: 27.0% ± 12.4% vs. 24.5% ± 10.6%, p = 0.428; PWV: 9.5 ± 2.1 m/s vs. 10.1 ± 3.1 m/s, p = 0.397). The slight difference in the estimation of aSBP is possibly explained by the difference in brachial SBP used for the calibration of the devices (131.0 ± 20.6 mmHg vs. 134.5 ± 19.7 mmHg, p = 0.525). Mobil-O-Graph-derived measurements correlated strongly with paired measurements obtained with the SphygmoCor device. Bland-Altman plots showed no evidence of asymmetry and a wide range of agreement between the two devices.Our study shows acceptable agreement between Mobil-O-Graph and SphygmoCor in the estimation of arterial stiffness indices in PD patients. Accordingly, the Mobil-O-Graph device accurately performs aortic ambulatory blood pressure monitoring in this population.

Bone Quality Assessment as Measured by Trabecular Bone Score in Patients With End-Stage Renal Disease on Dialysis.

Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) exhibit osteoporosis and increased fracture risk. Dual-energy X-ray absorptiometry scan measurements and calculation of fracture risk assessment toll score underestimate fracture risk in these patients and do not estimate bone quality. Trabecular bone score (TBS) has been recently proposed as an indirect measure of bone microarchitecture. In this study, we investigated alterations of bone quality in patients with ESRD on HD, using TBS. Fifty patients with ESRD on HD, with a mean age 62 years, and 52 healthy individuals matched for age, body mass index, and gender, were enrolled. All participants had a bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry scan at the lumbar spine, femoral neck, total hip, and 1/3 radius. TBS was evaluated using TBS iNsight. Serum fetuin-A and plasma fibroblast growth factor-23 (FGF-23) (C-terminal) were also measured. Patients on dialysis had significantly lower BMD values at all skeletal sites measured. Plasma FGF-23 levels significantly increased and serum fetuin-Α significantly decreased in patients on dialysis compared with controls. TBS was significantly reduced in patients on dialysis compared with controls (1.11 ± 0.16 vs 1.30 ± 0.13, p < 0.001, respectively) independently of age; BMD; duration of dialysis; and serum levels of alkaline phosphatase, 25-OH-vitamin D, parathyroid hormone, fetuin-A, or plasma FGF-23. Patients on HD who were diagnosed with an osteoporotic vertebral fracture had numerically lower TBS values, albeit without reaching statistical significance, compared with patients on dialysis without a fracture (1.044 ± 0.151 vs 1.124 ± 0.173, respectively, p = 0.079). Bone microarchitecture, as assessed by TBS, is significantly altered in ESRD on patients on HD independently of BMD values and metabolic changes that reflect chronic kidney disease-mineral and bone disorder.

Insulin Secretion and Resistance in Normoglycemic Patients with Sickle Cell Disease.

Diabetes mellitus has been described in chronic hemolytic anemias, but data are scarce regarding glucose metabolism in normoglycemic patients. To address this issue, we evaluated insulin sensitivity and secretion in patients with sickle cell disease (SCD) and normal oral glucose tolerance test (OGTT). Forty-five adult patients with homozygous sickle cell disease and Hb S/ß-thalassemia (ß-thal) (mean age 42.5 ± 9.5 years) and 45 healthy individuals matched for age and body mass index (BMI) were included in the study. All participants underwent an oral glucose tolerance test (OGTT) after an overnight fast. All patients had normal OGTT. Fasting glucose values did not differ significantly between groups, however, fasting insulin levels were significantly lower in the patient group compared to the control group (5.1 ± 2.7 µUI/mL vs. 11.3 ± 6.6 µUI/mL, p <0.005, respectively). Pancreatic ß-cell insulin secretion index in the fasting state was significantly lower in patients with sickle cell disease compared with controls as assessed by calculations of the homeostatic model assessment for ß-cell function (HOMA ß%) (77.0 vs. 106.0%, respectively, p <0.001), while HOMA insulin resistance (HOMA IR), was lower in the sickle cell disease patients, albeit not statistically significant (0.8 vs. 1.1, respectively, p = 0.054). The HOMA ß% was significantly correlated with ferritin levels (r = -526, p <0.001) (negative correlation) and with 25-hydroxy (OH)-vitamin D levels (r = 0.479, p <0.001) (positive correlation), even when adjusted for serum ferritin levels. Normoglycemic patients with sickle cell disease demonstrated impaired ß-cell function with reduced insulin secretion even before OGTT was impaired.

The Contribution of Osteoprogenitor Cells to Arterial Stiffness and Hypertension.

Hypertension, the major cause of cardiovascular disease, is bidirectionally linked to arterial stiffness. Evidence shows that vascular calcification, either medial or intimal, induces arterial stiffening further worsening hypertension parallel to substantially increasing cardiovascular risk. The disturbance in the bone-vascular axis that leads to the increase of calcium deposition in the arterial wall may be the result of a shift in the functionality of bone marrow-derived circulating stem cells with a calcifying potential, namely osteoprogenitor cells. These cells deposit bone matrix proteins in the vascular wall that can subsequently become mineralized. The current notion is that these cells derive from diverse cell lines. The present review summarizes the current knowledge on the role of progenitor cells with a calcifying potential on arterial calcification, stiffness and hypertension.

Anti-osteoporotic drugs and vascular calcification: the bidirectional calcium traffic.

During the last years, numerous epidemiological studies have demonstrated a direct relationship between vascular calcification and low bone mineral density. This observation is in line with experimental data demonstrating the osteogenic characteristics of calcified arteries. Various common risk factors have been suggested to link vascular calcification and bone loss, including aging, estrogen deficiency, vitamin D and K deficiency, diabetes mellitus, renal failure, smoking, chronic inflammation and oxidative stress. Although the underlying pathogenetic mechanisms are not yet clear, current research is focusing on anti-osteoporotic agents that could potentially affect the deposition of calcium in the arterial wall and thus provide an additional therapeutic strategy in elderly osteoporotic women prone to calcific cardiovascular disease.

Can antihypertensive medication interfere with the vicious cycle between hypertension and vascular calcification?

Vascular calcification is a phenomenon of disturbed calcium deposition, as part of the calcium that is supposed to be deposited to our bones, is lodged to our vessels. There are two forms of vascular calcification, each with a distinct anatomical distribution and clinical relevance, namely the intimal and medial calcification. Studies have demonstrated that hypertension may cause vascular calcification but also that both types of calcification, especially medial, promote arterial rigidity and hence hypertension. Implications of this two-way road are largely unknown as there is no consensus yet on their exact clinical value. However, several antihypertensive medications seem to be able to interfere with the cycle of high blood pressure and vascular calcium deposits. The present review summarizes the up-to-date data regarding the effect of antihypertensive medication on vascular calcification.

Prevalence, awareness, and control of hypertension in Greece before and after the COVID-19 pandemic: May Measurement Month survey 2019-2022.

OBJECTIVE: The COVID-19 pandemic had an adverse impact on several cardiovascular risk factors. This study investigated the prevalence, awareness and treatment of hypertension in Greece before and after the pandemic. Data were collected in the context of the May Measurement Month (MMM) global survey initiated by the International Society of Hypertension. METHODS: Adult volunteers (age ≥ 18 years) were recruited through opportunistic screening in public areas across cities in Greece in 2019 and 2022. Medical history and triplicate sitting blood pressure (BP) measurements were taken using validated automated upper-arm cuff devices. The data were uploaded to the international MMM cloud platform. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic ≥90 mm Hg and/or self-reported use of drugs for hypertension. The same threshold was used to define uncontrolled BP in treated individuals. RESULTS: Data from 12,080 adults were collected (5,727/6,353 in MMM 2019/2022; men 46/49%, p < 0.01; mean age 52.7 ± 16.6/54.8 ± 16.2, p < 0.001; smokers, 24.7/30.5, p < 0.001; diabetics 12/11.5%, p = NS; cardiovascular disease 5/5.8%, p = NS). The prevalence of hypertension was 41.6/42.6% (MMM 2019/2022, p = NS), with 21.3/27.5% of individuals with hypertension being unaware of their condition (p < 0.001), 5.6/2.4% aware untreated (p < 0.001), 24.8/22.1% treated uncontrolled (p < 0.05), and 48.3/47.8% treated controlled (p = NS). CONCLUSION: In Greece, the COVID-19 pandemic did not appear to affect the prevalence and control of hypertension; however, the rate of undiagnosed hypertension was higher after the pandemic. National strategies need to be implemented for the early detection and optimal management of hypertension in the general population in Greece.

Prevalence, recurrence and seasonal variation of hyperkalemia among patients on hemodialysis.

PURPOSE: Observational studies have shown that among patients on hemodialysis, hyperkalemia is strongly associated with excess risk for cardiovascular-related hospitalizations and sudden cardiac death. However, the actual burden of hyperkalemia, the rates of its recurrence and seasonality in its variation still remain unclear. METHODS: Between June 2020 and May 2021, 1786 mid-week pre-dialysis serum potassium (sK) measurements were retrospectively recorded from 149 patients receiving thrice-weekly hemodialysis in a single-center in Thessaloniki, Greece. The prevalence, recurrence and seasonal variation of hyperkalemia were assessed using three pre-specified sK thresholds (≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L). RESULTS: At baseline, 60.4%, 42.2% and 13.4% of patients had sK levels ≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L, respectively. At any time-point during follow-up, 85.2%, 69.8% and 38.9% of patients experienced at least one hyperkalemic event ≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L, respectively. Of the 104 patients experiencing an initial sK elevation ≥ 5.5 mmol/L, hyperkalemia at the same threshold reoccurred in 60.6% at month 1, in 47.1% at month 2 and in 46.1% at month 3 of follow-up. Seasonal variation was also observed, with the prevalence of hyperkalemia to be significantly higher in summer. Shorter delivered hemodialysis < 4 h/session (OR: 2.568; 95% CI 1.045-6.313) and the use of a high dialysate K concentration (OR: 14.646; 95% CI 2.727-78.647) were the 2 factors that were independently associated with hyperkalemia. CONCLUSION: The present study shows that among hemodialysis patients, the rates of hyperkalemia prevalence and recurrence are very high, reflecting the large unmet need to identify more effective potassium-lowering therapeutic interventions in this high-risk population.

Circulating microRNAs Related to Bone Metabolism in HIV-Associated Bone Loss.

The pathophysiology of human immunodeficiency virus (HIV)-associated bone loss is complex and to date largely unknown. In this study, we investigated serum expression of microRNAS (miRNAs) linked to bone metabolism in HIV-associated bone loss. This was a case-control study. Thirty male individuals with HIV infection (HIV+) and osteoporosis/osteopenia (HIV+/OP+) (cases) and 30 age-matched male HIV+ individuals with normal bone mass (HIV+/OP-) (controls) were included in the analysis. Thirty male individuals matched for age without HIV infection (HIV-), were also included as second controls. The selected panel of miRNAs was as follows: hsa-miRNA-21-5p; hsa-miRNA-23a-3p; hsa-miRNA-24-2-5p; hsa-miRNA-26a-5p; hsa-miRNA-29a-3p; hsa-miRNA-124-3p; hsa-miRNA-33a-5p; and hsa-miRNA-133a-3p. Within the cohort of HIV+ individuals, relative serum expression of miRNA-21-5p and miRNA-23a-3p was significantly lower (p < 0.001) while the expression of miRNA-24-2-5p was significantly higher (p = 0.030) in HIV+/OP+ compared to HIV+/OP-. Expression of miRNA-21-5p demonstrated a sensitivity of 84.6% and a specificity of 66.7 in distinguishing HIV+/OP+ individuals. Expression of circulating miRNAs related to bone metabolism; miRNA-23a-3p, miRNA-24-2-5p, and miRNA-21-5p is significantly altered in HIV+OP+ individuals, in line with data on other causes of osteoporosis, suggesting a common pattern of circulating miRNAs independent of the underlying cause.

Beneficial effects of oral magnesium supplementation on insulin sensitivity and serum lipid profile.

BACKGROUND: Epidemiological studies have associated low dietary Mg2+ intake with insulin resistance (IR) and increased risk for metabolic syndrome; however, the effect of Mg2+ supplementation on IR has not been adequately investigated. This study aimed to investigate the effects of oral Mg2+ supplementation on insulin sensitivity (IS) and serum lipids.
MATERIAL/METHODS: Forty-eight patients with mild uncomplicated hypertension participated in the study. Among them, 24 subjects were assigned to 600 mg of pidolate Mg2+ daily in addition to lifestyle recommendations for a 12-week period, and another 24 age- and sex-matched controls were only given lifestyle recommendations. At baseline and study-end, blood sampling for determination of fasting glucose and insulin levels, serum lipids and other standard laboratory tests, as well as an oral glucose tolerance test (OGTT) for estimation of IS indices, were performed in all subjects.
RESULTS: In the Mg2+ supplementation group the OGTT-derived IS indices of Stumvoll, Matsuda and Cedercholm in were increased between baseline baseline and study-end. In contrast, none of these parameters were changed in the control group. Reductions in total cholesterol, LDL-cholesterol and triglyceride levels, along with a parallel increase in HDL-cholesterol levels, were evident at study-end in the intervention group, but not in the control group.
CONCLUSIONS: This study suggests that oral Mg2+ supplementation improves IS and lipid profile in mildly hypertensive patients. These potential beneficial effects of Mg2+ on associated metabolic factors could be helpful for patients with hypertension in terms of overall cardiovascular risk reduction.

Association of Elevated Blood Pressure Levels with Outcomes in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Although arbitrary blood pressure (BP) thresholds exist for acute ischemic stroke (AIS) patients eligible for intravenous thrombolysis (IVT), current international recommendations lack clarity on the impact of mean pre- and post-IVT BP levels on clinical outcomes. METHODS: Eligible studies involving IVT-treated AIS patients were identified that reported the association of mean systolic BP (SBP) or diastolic BP levels before and after IVT with the following outcomes: 3-month favorable functional outcome (modified Rankin Scale [mRS] scores of 0-1) and 3-month functional independence (mRS scores of 0-2), 3-month mortality and symptomatic intracranial hemorrhage (sICH). Unadjusted analyses of standardized mean differences and adjusted analyses of studies reporting odds ratios (ORadj) per 10 mm Hg BP increment were performed using random-effects models. RESULTS: We identified 26 studies comprising 56,513 patients. Higher pre- (P=0.02) and posttreatment (P=0.006) SBP levels were observed in patients with sICH. Patients with 3-month functional independence had lower post-treatment (P<0.001) SBP whereas trended towards lower pre-treatment (P=0.06) SBP. In adjusted analyses, elevated pre- (ORadj, 1.08; 95% confidence interval [CI], 1.01 to 1.16) and post-treatment (ORadj, 1.13; 95% CI, 1.01 to 1.25) SBP levels were associated with increased likelihood of sICH. Increasing pre- (ORadj, 0.91; 95% CI, 0.84 to 0.98) and post-treatment (ORadj, 0.70; 95% CI, 0.57 to 0.87) SBP values were also related to lower odds of 3-month functional independence. CONCLUSION: s We found that elevated BP levels adversely impact AIS outcomes in patients receiving IVT. Future randomized-controlled clinical trials will provide definitive data on the aforementioned association.

Clinical and Neuroimaging Characteristics in Embolic Stroke of Undetermined versus Cardioembolic Origin: A Population-Based Study.

BACKGROUND AND PURPOSE: Evidence suggests that cardioembolism represents the underlying mechanism in the minority of embolic strokes of undetermined source (ESUS). In this population-based study, we sought to compare the clinical and imaging characteristics as well as outcomes in patients with ESUS and cardioembolic stroke (CE). METHODS: We included consecutive patients with first-ever ischemic stroke (IS) from the previously published population-based Evros-Stroke-Registry identified as ESUS or CE according to standardized criteria. Baseline characteristics, admission NIHSS scores, cerebral edema, hemorrhagic transformation, stroke recurrence, functional outcomes (determined by modified Rankin Scale [mRS] scores), and mortality rates were recorded during the 1-year follow-up period. RESULTS: We identified 21 ESUS (3.7% of IS) and 211 CE (37.1% of IS) cases. Patients with ESUS were younger (median age: 68 years [interquartile range [IQR]: 61-75] vs 80 years [IQR: 75-84]; P < .001), had lower median admission NIHSS scores (4 points [IQR: 2-8] vs 10 points [IQR: 5-17]; P < .001), and lower prevalence of cerebral edema on neuroimaging studies (0 vs. 33.3%, P = .002). Functional outcomes were more favorable in ESUS at 28 (median mRS score: 2 [IQR: 1-3] vs 4 [IQR: 4-5]; P < .001), 90 (median mRS score: 1 [IQR: 0-2] vs 4 [IQR: 3-5]; P < .001), and 365 days (median mRS score: 1 [IQR: 0-2] vs 4 [IQR: 2-4]; P < 0.001). At 1-year, the mortality rate was lower in ESUS (0% [95% confidence interval [CI]: 0-13.5%] vs 34.6% [95% CI: 28.2-41.0%]; P < .001); the 1-year recurrent rate was also lower numerically (0% [95% CI: 0-13.5%] vs 9.5% [95% CI: 5.5-13.4%]; P = .140) but this difference failed to reach statistical significance due to the small study population. CONCLUSIONS: The clinical and neuroimaging profiles as well as clinical outcomes vary substantially between ESUS and CE indicating different underlying mechanisms.

Incidence, characteristics and outcomes in patients with embolic stroke of undetermined source: A population-based study.

Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10-25) and 16.6 (95%CI: 10-24) per 100,000 person-years. Patients with ESUS were younger (p < .001) and had lower median admission NIHSS-scores (p < .001). Functional outcomes were more favorable in ESUS at 28, 90 and 365 days. ESUS was independently (p = .033) associated with lower admission NIHSS-scores (unstandardized linear regression coefficient: -13.34;95%CI: -23.34, -3.35) on multiple linear regression models. ESUS was not related to 1-year stroke recurrence, mortality and functional improvement on multivariable analyses. In conclusion we found that ESUS cases represented 8% of CS patients in this population-based study. Despite the fact that ESUS was independently related to lower admission stroke severity, there was no association of ESUS with long-term outcomes.

Arterial stiffness in end-stage renal disease-pathogenesis, clinical epidemiology, and therapeutic potentials.

Arterial stiffness is an important risk factor for cardiovascular morbidity and mortality in patients with end-stage renal disease (ESRD). Arterial stiffness aggravates cardiovascular risk via multiple pathways, such as augmentation of aortic systolic pressure, subendocardial hypoperfusion, and excess pulsatile energy transmission from macro- to microcirculation. Pathogenesis of the arteriosclerotic process in ESRD is complex and not yet fully understood. Several factors unique to ESRD, such as mineral metabolism disturbances, vascular calcifications, formation of advanced glycation end-products, and acute and chronic volume overload, are proposed to play a particular role in the progression of arteriosclerosis in ESRD. As these and other mechanistic pathways of arterial stiffening in ESRD are elucidated, there is hope that this knowledge will be translated into novel therapeutic interventions targeting arterial stiffness. In the meantime, blood pressure (BP) lowering via strict volume control and appropriate use of antihypertensive drugs is a fundamental step in reversing accelerated arterial stiffening and modifying the cardiovascular risk profile of ESRD patients. In this article, we review the pathogenesis, clinical epidemiology, and therapies targeting arterial stiffness in ESRD, discussing recent advances and high-priority goals of future research in these important areas.

Changes of Circulating MicroRNAs in Response to Treatment With Teriparatide or Denosumab in Postmenopausal Osteoporosis.

Context: Expression of microRNAs (miRs) related to bone metabolism in the serum may be affected by antiosteoporotic treatment. Objective: To investigate the effect of two antiosteoporotic agents with opposite effects on bone metabolism on miR expression profile in the serum. Design: Observational, open label, nonrandomized clinical trial. Setting: The outpatient clinics for Metabolic Bone Diseases of 424 General Military Hospital, Thessaloniki, Greece. Patients and Interventions: Postmenopausal women with low bone mass were treated with either teriparatide (TPTD; n = 30) or denosumab (n = 30) for 12 months. Main Outcome Measures: Changes in the serum expression of selected miRs linked to bone metabolism at 3 and 12 months of treatment. Secondary measurements: associations of measured miRs with changes in bone mineral density (BMD) at 12 months and the bone turnover markers (BTMs) C-terminal cross-linking telopeptide of type I collagen and procollagen type I N-terminal propeptide at 3 and 12 months. Results: We found significantly decreased relative expression of miR-33-3p at 3 months (P = 0.03) and of miR-133a at 12 months (P = 0.042) of TPTD treatment. BMD values at 12 months of TPTD treatment were significantly and inversely correlated with miR-124-3p expression at 3 months (P = 0.008). Relative expression of miR-24-3p and miR-27a was correlated with changes in BTMs during TPTD treatment and of miR-21-5p, miR-23a-3p, miR-26a-5p, miR-27a, miR-222-5p, and miR-335-5p with changes in BTMs during denosumab treatment. Conclusions: Circulating miRs are differentially affected by treatment with TPTD and denosumab. TPTD affects the relative expression of miRs related to the expression of RUNX-2 (miR-33) and DKK-1 gene (miR-133).

Stroke recurrence and mortality in northeastern Greece: the Evros Stroke Registry.

Up to date there is no population-based study from Greece providing long-term data on incidence of both all-cause mortality and stroke recurrence for patients with first ever stroke (FES). Adult patients with FES were registered during a 24-month period (2010-2012) and followed-up for 12 months. We calculated cumulative incidences of stroke mortality and recurrence. Univariable and multivariable Cox proportional hazards regression analyses were used to identify independent determinants of 1-year mortality and 1-year stroke recurrence. We prospectively documented 703 first ever stroke cases (mean age 75 ± 12 years; 52.8% males; ischemic stroke 80.8%, intracerebral hemorrhage 11.8%, subarachnoid hemorrhage 4.4%, undefined 3.0%) with a total follow-up time of 119,805 person-years. The cumulative incidence rates of mortality of all FES patients at 28 days, 3 months and 1 year were 21.3% (95% CI 18.5-24.5%), 26% (95% CI 22.9-29.4%) and 34.7% (95% CI 31.3-38.3%), respectively. The risk of 1-year mortality was independently (p < 0.05) associated with advancing age, history of hypertension, increased stroke severity on admission, and hemorrhagic FES type. Cumulative 1-year stroke mortality differed according to both index FES type (ischemic vs. hemorrhage; p < 0.001), but also across different ischemic stroke subtypes (p = 0.025). The cumulative incidence rates of recurrent stroke at 28 days, 3 months and 1 year were 2.0% (95% CI 1.2-3.6%), 4.2% (2.8-6.2%) and 6.7% (5.1-8.8%), respectively. Comparable to other population-based surveys, our study reports 1-year mortality and stroke recurrence rates in patients with FES. These findings highlight the need for effective secondary prevention strategies in a border region of southeastern Europe, which exhibits very high FES incidence rates.

Blood pressure and serum potassium levels in hypertensive patients receiving or not receiving antihypertensive treatment.

OBJECTIVE: Serum potassium has a fundamental role in blood pressure (BP) regulation, and there is evidence highlighting the importance of potassium homeostasis in hypertension. The aim of this study was to determine the relationship between serum potassium levels and office BP in untreated essential hypertensives and the effect of antihypertensive medication on serum potassium levels. SETTING AND PARTICIPANTS: In a retrospective analysis, we collected data for consecutive patients first visiting our Hypertension Clinic from 1999-2004. From this population, we first selected patients who were not taking any antihypertensive medication. Patients who had conditions that could affect potassium metabolism, such as history of arrhythmias treated with digitalis, diabetes mellitus under insulin treatment, and hypo- and hyperthyroidism, were excluded from the study. From the remaining patients, those who had impaired renal function (serum creatinine > or = 1.6 mg/dL for men and > or = 1.4 mg/dl for women) and patients with secondary forms of hypertension were also excluded. The final population consisted of 817 subjects. Multivariate linear regression analysis was applied, and models were created associating serum potassium with systolic BP, diastolic BP, mean BP, or pulse pressure. The population for the second part of the study consisted of patients first visiting our Hypertension Clinic who were on one antihypertensive agent. This second group included 757 patients, 218 of whom were on beta-blockers, 42 on diuretics, 187 on angiotensin-converting enzyme (ACE) inhibitors, 287 on calcium channel blockers (CCBs), and 28 on angiotensin receptor blockers (ARBs). RESULTS: After adjusting for age, gender, and body mass index, significant negative correlations were found between serum potassium levels and systolic BP (R = -0.093, p = 0.007), diastolic BP (R = -0.078, p = 0.03), mean BP (R = -0.122, p = 0.002), and pulse pressure (R = -0.071, p = 0.044). The levels of potassium were found to be significantly lower among patients receiving diuretics than those receiving one of the other four drug categories of antihypertensive (p < 0.05 for beta-blockers, ACE inhibitors, and CCBs; p < 0.001 for ARBs). In addition, hypokalemia was found to be significantly more prevalent in the group using diuretics than the other groups. CONCLUSIONS: The observed reverse relation between serum potassium and BP supports a close pathophysiological connection between serum potassium and essential hypertension. Moreover, diuretic therapy is a significant cause of hypokalemia and requires systematic monitoring.