Antihypertensive Treatment Research Articles

Sympathetic overactivity and nocturnal diuresis in obstructive sleep apnea alter the response to hypertension therapy

BackgroundObstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy.Methods and resultsForty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P < 0.05). Nighttime systolic blood pressure dipping was poor at 6.6 ± 1.8%. Hydrochlorothiazide did not alter blood pressure dipping but guanfacine improved dipping to 9.1 ± 1.2%, a better result (P = 0.03) than from the diuretic. Central aortic pressure by pulse wave analysis was 120/84 mmHg on hydrochlorothiazide and 109/72 on guanfacine, (P < 0.05). Guanfacine, but not hydrochlorothiazide, improved baroreflex sensitivity, heart rate variability and flow mediated vascular dilation, suggesting that decreasing the elevated sympathetic nerve activity of obstructive sleep apnea returned vascular function toward normal.ConclusionsOSA is the most common condition associated with antihypertensive treatment failure. It increased sympathetic nerve activity day and night. Drugs that block sympathetic nerve function are not among the 4 most commonly recommended classes of antihypertensives but diuretics are. Sympatholytic therapy was superior to diuretic treatment for hypertension associated with sleep apnea.Trial registrationNCT, NCT02699125, Registered 26 February 2016 - Retrospectively registered, https://clinicaltrials.gov/study/NCT02699125.

Disability level’s impact on blood pressure-mortality association in older long-term care adults: evidence from a large Chinese cohort study

BackgroundEvidence of the optimal blood pressure (BP) target for older adults with disability in long-term care is limited. We aim to analyze the associations of BP with mortality in older adults in long-term care setting with different levels of disability.MethodsThis prospective cohort study was based on the government-led long-term care programme in Chengdu, China, including 41,004 consecutive disabled adults aged ≥ 60 years. BP was measured during the baseline survey by trained medical personnel using electronic sphygmomanometers. Disability profile was assessed using the Barthel index. The association between blood pressure and mortality was analyzed with doubly robust estimation, which combined exposure model by inverse probability weighting and outcome model fitted with Cox regression. The non-linearity was examined by restricted cubic spline. The primary endpoint was all-cause mortality, and the secondary endpoints were cardiovascular and non-cardiovascular mortality.ResultsThe associations between systolic blood pressure (SBP) and all-cause mortality were close to a U-shaped curve in mild-moderate disability group (Barthel index ≥ 40), and a reversed J-shaped in severe disability group (Barthel index < 40). In mild-moderate disability group, SBP < 135 mmHg was associated with elevated all-cause mortality risks (HR 1.21, 95% CI, 1.10–1.33), compared to SBP between 135 and 150 mmHg. In severe disability group, SBP < 150 mmHg increased all-cause mortality risks (HR 1.21, 95% CI, 1.16–1.27), compared to SBP between 150 and 170 mmHg. The associations were robust in subgroup analyses in terms of age, gender, cardiovascular comorbidity and antihypertensive treatment. Diastolic blood pressure (DBP) < 67 mmHg (HR 1.29, 95% CI, 1.18–1.42) in mild-moderate disability group and < 79 mmHg (HR 1.15, 95% CI, 1.11–1.20) in severe disability group both demonstrated an increased all-cause mortality risk.ConclusionThe optimal SBP range was found to be higher in older individuals in long-term care with severe disability (150-170mmHg) compared to those with mild to moderate disability (135-150mmHg). This study provides new evidence that antihypertensive treatment should be administered cautiously in severe disability group in long-term care setting. Additionally, assessment of disability using the Barthel index can serve as a valuable tool in customizing the optimal BP management strategy.Trial registrationChinese Clinical Trial Registry (Registration Number: ChiCTR2100049973).

Isolated systolic hypertension in young adults and its relationship with ambulatory blood pressure measurements

Introduction: The definition of Isolated Systolic Hypertension (ISH) is accepted by guidelines, which adopt a blood pressure (BP) cutoff point of 140/90 mmHg, with elevated Systolic Blood Pressure (SBP) and normal diastolic blood pressure (DBP) in the clinic. This phenotype represents the most common form of Hypertension (HT) in young individuals. The prognosis of ISH differs according to various explanatory mechanisms. Some associations of this phenotype with Ambulatory Blood Pressure Monitoring (ABPM) have been described, but little emphasis has been placed on its association with nocturnal BP values. To the best of our knowledge, there is no epidemiological data on young patients establishing this relationship in Latin America. Objective: To describe the characteristics of ISH in our population of young patients and analyze its relationship with different ABPM phenotypes. Materials and methods: Consecutive adult individuals between 16 and 40 years of age, without antihypertensive treatment, were evaluated in a cross-sectional study. They were referred for ABPM to a tertiary hospital between July 2013 and August 2022. Each individual underwent an initial interview, three BP measurements using current standards with OMROM HEM 705 devices, and subsequent ABPM with Spacelabs 90207. A general description of the sample was provided, and an analysis was conducted based on different patient phenotypes determined by clinic BP measurements in relation to various ABPM phenotypes. Results: A total of 395 individuals (69% women, 29 ± 6.5 years) were finally evaluated. The frequencies according to clinic phenotypes were as follows: Normotensive = 77%, ISH = 6%, HT = 17%. Among the ISH group, 29.2% had white coat hypertension (WCH). The Kappa agreement was 31% for clinic phenotypes vs. ABPM. Among ISH patients, 37% had at least one elevated period (daytime or nighttime), and 12.5% had elevated BP only during the nighttime.

Habitual Regular Coffee Consumption and Arterial Stiffness: Data From the 3rd Pamela Survey.

We evaluated whether chronic coffee consumption affects arterial stiffness, assessed by cardio-ankle vascular index (CAVI). In 514 subjects, aged 66.6 ± 9.9 years (mean ± SD), recruited in the 3rd follow-up of the PAMELA study, subdivided into 3 groups according to the daily intake of regular coffee (0, 1-2, and ≥3 cups/day), we measured CAVI and clinic, ambulatory blood pressure (BP), and other variables. The 3 groups displayed similar age, gender, metabolic, and renal profile. Clinic and ambulatory BPs were similar in the 3 groups, this being the case for CAVI (0 cup: 9.1 ± 1.8, 1-2 cups: 9.5 ± 2.3, and ≥3 cups: 9.2 ± 2.1 m/s, P = NS). No significant gender difference in CAVI and in participants under antihypertensive treatment was detected. Our data show that chronic coffee consumption leaves unaffected arterial stiffness in the general population, this being the case in subgroups. The neutral vascular impact of coffee may favor the absence of any significant BP effect of habitual coffee intake.

Blood pressure monitoring in elderly migraineurs starting an anti-CGRP monoclonal antibody: a real-world prospective study

BackgroundWhile monoclonal antibodies (mAbs) targeting the CGRP pathway have revolutionized migraine management due to their improved tolerance and adherence, concerns remain about their potential impact on blood pressure (BP), especially in older patients, due to CGRP-mediated vasodilation blockade. Given the growing use of these therapies in older populations, assessing their cardiovascular (CV) safety is of paramount importance.MethodsThis multicentric observational prospective study focused on migraine sufferers aged ≥ 60 who began erenumab, galcanezumab, or fremanezumab for prevention. Baseline, three-month, and twelve-month BP measurements were collected. Changes in antihypertensive medication and "Newly or Worsened Hypertensive" patients (NWHP) were assessed.ResultsAmong 155 patients receiving anti-CGRP mAbs (40 Erenumab, 47 Galcanezumab, 68 Fremanezumab), 42.5% had hypertension history and 39% were on antihypertensive treatment. No significant systolic or diastolic BP changes occurred at any time point compared to baseline (all p > 0.05), with no differences between the three groups. After one year, 20/155 (12.9%) patients were considered NWHP; 11/20 had prior hypertension, and 5/11 adjusted antihypertensive therapy. Among 9/20 newly hypertensive patients, 5/9 had a single measurement above the normal threshold with no requirement for new pharmacological therapy. A higher baseline BP value was associated with increased BP (p = 0.002).ConclusionsThe study concludes that treatment with anti-CGRP mAbs over one year does not significantly affect BP in patients aged ≥ 60, nor does it increase the incidence of hypertension compared to general population trends. Nonetheless, continuous monitoring and further long-term studies are necessary to fullya scertain the cardiovascular safety of these medications in the elderly.

Dietary sodium intake and atrial myopathy

Abstract Background Diagnostic markers associated with atrial cardiomyopathy, a precursor state to atrial fibrillation (AF), include premature atrial complex (PACs) frequency, left atrial volume index (LAVi) and p-wave indices. Life-style factors associated with atrial myopathy markers are insufficiently studied. Sodium intake is a modifiable risk factor for hypertension, cardiovascular disease and AF. Purpose We aimed to study the association between sodium intake and atrial myopathy markers in the population-based multicenter Swedish CArdioPulmonary bioImage Study. Methods We included 5,309 randomly invited 50–65-year-olds at the Malmö (n=1,125,) and Uppsala sites (n=4,184) without AF who had contributed a 24hECG and a fasting morning urine sample, from which daily sodium intake was estimated using the Kawasaki formula. At the Malmö site resting ECGs from which P-wave indices could be measured were available in 1,066 individuals, and LAVi was available in a random subsample (n=357). The association between sodium intake and atrial myopathy markers was modeled adjusted for age, sex, body mass index, smoking, systolic blood pressure, antihypertensive treatment, coronary artery disease, and heart failure using negative binomial regression for PAC frequency, linear regression for P-wave duration and LAVi and logistic regression for P-wave terminal force in V1, all using sodium intake as a continuous variable and strata at &amp;lt;2, 2.0-2.99g, 3.0-3.99g, 4.0-4.99g and ≥5 g/day, with 3.0-3.99 as the reference category. We also modeled the association between sodium intake and PACs using restricted cubic splines. Results The mean age was 58.1 (±4.1) years, and 52.7% were female. The mean estimated sodium intake was 3.3 (±1.4) g/day. Mean 24h PAC count was 27, 4.7% had ≥500 PACs. High sodium intakes were associated with increased PAC frequency, of 14% (95% confidence interval (CI 1-29% p=0.03)) for 4.0-4.99g/day and 25% (95%CI 8-45%, p=0.002) for intakes ≥5.0g/day, compared to sodium intakes of 3.0-3.99 g/day. There was no significant association between low sodium intakes (&amp;lt;3.0 g/day) and PACs, Figure 1. Sodium intakes of 4.0-4.99 g/day were associated with increased P-wave duration, ß-coefficient 2.4 (95%CI 0.3-4.1, p=0.03), compared to 3.0-3.99g/day, but there was no association between sodium intakes and LAVi, or P-wave terminal force in V1, either as a continuous variable or in strata. Conclusion High dietary sodium intake is associated with PAC frequency, a known prediction of AF and stroke. Whether reduced sodium diets could reduce PAC frequency, and whether that would impact AF and stroke risk needs further study.Sodium intake and PAC frequency

#664 Childhood Takayasu arteritis: a multicentre retrospective study

Abstract Background and Aims Takayasu arteritis (TA) is a rare, large vessel vasculitis affecting mainly the aorta and its major branches. Data on paediatric TA (pTA) is very scarce. The aim of this study was to characterize clinical presentation, therapy and outcome of pTA in a global study population. Method We conducted an international multicentre retrospective observational study of children diagnosed with pTA. Inclusion criteria were an age of less than 18 years at initial presentation in the year 2000 or more recently. Clinical data were collected from patients’ charts by the treating paediatric rheumatologist or nephrologist; data were fully anonymised for analysis purposes. Follow-up data was collected up to 2 years after diagnosis. Results 198 patients from 20 countries were included (76% female). The median age at disease onset was 12 years. Arterial hypertension (67%), a difference in pulses between limbs (65%) and fatigue (66%) were the most common symptoms at presentation. The gastrointestinal system was the second most affected organ system. The median eGFR (estimated glomerular filtration rate) at baseline was 105 ml/min/1.73 m2. Renal artery stenosis was documented in 58% of all patients and in 37% there was need for an invasive renovascular procedure. In 25 of 32 (78%) patients who had either a positron emission tomography–magnetic resonance imaging (PET-MRI) or PET-computed tomography (CT) there was evidence of active inflammation mainly of the aorta. 67% of all patients showed thickened wall abnormalities and 31% had arterial dilatations in a major vessel on any one or more anatomical imaging modality such as ultrasound, CT or MRI. Immunosuppressive treatment was primarily steroids, cyclophosphamide and methotrexate, 37% of all patients were treated with monoclonal antibodies of which 65% received an anti-tumor necrosis factor (TNF) antibody, 31% an anti-Interleukin 6 (IL-6) antibody and 4% an anti-B-cell antibody. Dialysis was necessary in 7% and one patient underwent kidney transplantation. Seven patient deaths (4%) were documented at the most recent follow-up. The renal function after two years was median eGFR 102 ml/min/1.73 m2, with 67% showing normal function, 31% presenting with chronic kidney disease (CKD) stage 1, 1% with stage 2, 1% with stage 3 and no patients showed stages 4 and 5. A quarter of the patients (27%) were still symptomatic at the 2-year follow-up. The median systolic blood pressure was 117 (interquartile range 107–125) mmHg. 64% of all patients still had antihypertensive treatment, and 87% were still on immunosuppressive therapy. Conclusion Our study represents the largest paediatric cohort of children diagnosed with Takayasu arteritis. Several organ systems were involved at onset and the clinical spectrum was highly variable. We will in our further analyses in more detail describe the outcome in relation to presenting symptoms and treatment.

#2991 Two cases of chronic lymphocytic leukemia associated immunotactoid glomerulopathy: variable clinical presentation, close hematological collaboration

Abstract Background and Aims Immunotactoid glomerulopathy (ITG) is a very rare disease, observable in less than 0.1% of native kidney biopsy samples. It is most often associated with hematological diseases. We confirmed ITG in two cases among our 850 kidney biopsy patients in the past 9 years. In both patients, chronic lymphocytic leukemia (CLL) was the underlying cause. Method Case 1, a 56-year-old man was admitted due to severely increased proteinuria (2 g/day) with preserved renal function, while case 2, a 57-year-old-man was referred with rapidly decreasing eGFR (20 ml/min/1.73m2) with nephrotic syndrome (serum albumin level was 24 g/l). In case 1, no previous history of hematological disease was known, in case 2, CLL - that did not require treatment - was diagnosed half a year before admission. He still had no kidney involvement even 3 months after the CLL diagnosis. We performed kidney biopsy. Light microscopy revealed mesangial proliferative-atypical membranous pattern in case 1, and membranoproliferative pattern in case 2. Immunofluorescence microscopy showed IgG1-lambda deposition, electron microscopy confirmed the organised deposits, microtubular structures with a diameter of 44 nanometers in both cases. Neither monoclonal gammopathy nor systemic immune disease was confirmed. In case 2, low titer ANA positivity, low C3 and high anti-C1q antibody titer was detected, lupus nephritis was ruled out. Previously, lymphocyte count was slightly increased in case 1, CLL was confirmed after kidney biopsy. The immunoglobulin heavy chain variable region gene somatic hypermutation status was borderline in case 1, while in the other case it was unmutated. Fluorescein in situ hybridisation revealed trisomy 12 in both cases. In case 1, chemotherapy was not used due to Rai stage 0, and with appropriate antihypertensive treatment, we could preserve kidney function, and proteinuria was persistently low (below 1 g/day). In case 2, due to Rai stage 1, and progressive renal and lymph node involvement, immunochemotherapy was started (obinutuzumab-venetoclax). Three months later eGFR stabilized at 27 ml/min/1.73 m2, proteinuria decreased below 1 g/day, the C3 level normalized. Conclusion ITG can develop in the early stages of CLL, but it can also indicate CLL progression. The light microscopy histological pattern and, in parallel, the clinical appearance can be of varying severity. Immunochemotherapy resulting reduction of CLL tumor burden and cessation of complement damage, both play a role of improving renal status. Our cases also draw attention to the need for close collaboration with hematologists.

#2171 The impact of preoperative hypertension and blood pressure control on kidney outcomes after surgery for localized kidney cancer: a prospective study

Abstract Background and Aims Kidney surgery represents the treatment of choice for localized renal cell carcinomas (RCC). Postoperative acute kidney injury (AKI) is reported in 40% of the patients undergoing partial nephrectomy [1]. A nephron-sparing approach is not always feasible for anatomical as well as oncological reasons and total nephrectomy is associated with an even higher risk of both acute and chronic impairment of renal function. Recently, interest has risen in the development of prediction models able to preoperatively identify patients at higher risk of AKI and chronic kidney disease (CKD) development after kidney surgery, but the role of hypertension in this field is yet underexplored. The aim of the present study was therefore to assess the impact of hypertension and blood pressure control on kidney outcomes after surgery for RCC. Method We prospectively enrolled 45 patients with an estimated glomerular-filtration-rate (eGFR) &amp;gt; 45 ml/min per 1.73 m2 who underwent kidney surgery for RCC at our institution between May 1, 2022, and September 30, 2023. Clinical characteristics of the study cohort are reported in Table 1. In-hospital AKI was defined as an increase of serum creatinine &amp;gt; 0.3 mg/dl from baseline and CKD development (defined as eGFR &amp;lt;60 ml/min/1.73 m2) was evaluated at 3 months. Ambulatory blood pressure monitoring (24h-ABPM) was assessed at baseline. Comparisons between groups were made by analysis of variance. Comparisons of proportions among groups were made using the χ2 test. Multivariate logistic regression analysis was used to describe the relationship between clinical variables and the presence of in-hospital AKI. Results Among the 45 patients enrolled, 42% (n = 19) developed postoperative AKI, of whom 32% (n = 6) had a complete kidney function recovery, whereas 68% (n = 13) developed CKD. Of the 39 patients with a basal ABPM evaluation, 87% (n = 34) had a diagnosis of hypertension. For 35% (n = 12) of these patients a first diagnosis of hypertension was made. AKI patients had higher median SBP (143 ± 9 vs 133 ± 12 mmHg, p = 0.008) and SBP variability (24 ± 4 vs 20 ± 5 mmHg, p = 0.01) compared with non-AKI patients. Preoperative 24h-SBP &amp;gt;130 mmHg was independently associated with in-hospital AKI (p = 0.05), regardless of age, gender, hypertension, diabetes and antihypertensive treatment. Considering the 3-month eGFR, we observed that compared with non-AKI patients, baseline 24h-SBP was higher, as a trend, in AKI patients who did not develop CKD or in those developing CKD on previous normal kidney function (de novo CKD), while no difference in 24h-SBP was observed between AKI and non-AKI patients in the subgroup of patients with preoperative CKD (CKD on CKD) (Fig. 1). Conclusion Preoperative hypertension, a potentially modifiable risk factor, is associated with an increased risk of AKI after kidney surgery. Moreover, an early identification of hypertension is of utmost importance taking into account that a strict blood pressure control, regardless of renal function at baseline, may be crucial to counteract the development or the progression of CKD.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. ClinicalTrials.gov , NCT02299414.

Analysis of fetal heart rate fluctuations in women diagnosed with preeclampsia during the latent phase of labor

IntroductionFetal heart rate variability (fHRV) is a tool used to investigate the functioning of the fetal autonomic nervous system. Despite the significance of preeclampsia, fHRV during the latent phase of labor has not been extensively studied. This study aimed to evaluate fetal cardiac autonomic activity by using linear and nonlinear indices of fHRV analysis in women diagnosed with preeclampsia without hypertensive treatment during gestation, compared to normotensive women during the latent phase of labor.MethodsA cross-sectional and exploratory study was conducted among pregnant women in the latent phase of labor, forming three study groups: normotensive or control (C, 38.8 ± 1.3 weeks of pregnancy, n = 22), preeclampsia with moderate features (P, 37.6 ± 1.4 weeks of pregnancy n = 10), and preeclampsia with severe features (SP, 36.9 ± 1.2 weeks of pregnancy, n = 12). None of the participants received anti-hypertensive treatment during their pregnancy. Linear and nonlinear features of beat-to-beat fHRV, including temporal, frequency, symbolic dynamics, and entropy measures, were analyzed to compare normotensive and preeclamptic groups.ResultsSignificantly lower values of multiscale entropy (MSE) and short-term complexity index (Ci) were observed in the preeclamptic groups compared to the C group (p &amp;lt; 0.05). Additionally, higher values of SDNN (standard deviation of R-R intervals) and higher values of low-frequency power (LF) were found in the P group compared to the C group.ConclusionOur findings indicate that changes in the complexity of fetal heart rate fluctuations may indicate possible disruptions in the autonomic nervous system of fetuses in groups affected by undiagnosed preeclampsia during pregnancy. Reduced complexity and shifts in fetal autonomic cardiac activity could be associated with preeclampsia’s pathophysiological mechanisms during the latent phase of labor.

#1925 A rare cause of hyponatremia due to adrenal insufficiency in a patient with small cell lung cancer

Abstract Background and Aims Hyponatremia is the most frequent electrolyte disorder. Small Cell Lung Cancer (SCLC) release often antidiuretic hormone paraneoplastically. But Adrenal insufficiency is a rare cause of hyponatremia in SCLC. Prior one can cause euvolemic hyponatremia, latter one can cause hypovolemic hyponatremia. Opposite treatments should be applied for each one. So They should be investigated carefully before starting the treatment. Method A male patient who had metastatic SCLC was admitted to the emergency. After physical examination blood and urine tests were provided. Results A 52-year-old male patient who had metastatic SCLC was admitted to the emergency unit because of fatigue, weakness and confusion. On physical examination the patient's face was darkened but his conjunctiva was pale, his tongue and mucous membranes were dry. The blood pressure was 90/60 mm Hg. The test results provided were as follows: Glucose 106 mg/dL, creatinine 0.42 mg/dL, urea 38.1 mg/dL, sodium 109 mmol/L, potassium 3.3 mmol/L, white blood cells 9760 /mm3, hemoglobin: 9 g/dL, platelets: 176000/mm3. The patient had no chemotherapy during the last three months. He also did not have a history of antihypertensive treatment. The echocardiographic examination revealed that the ejection fraction was 60%. The abdominal computerized tomography scan showed multiple metastasis of the tumor, but adrenal glands were free of metastasis. The sodium deficit was calculated targeting to 120 mmol/L and therapy was started. The patient's weight was 70 kg. The calculated sodium deficit was 420 mmol. Since the hyponatremia was chronic, the deficit was planned to be given in 24 hours. Potassium was also given. During hospitalization, on day 2nd the patient's blood and urine tests were as follows: Creatinine 0.58 mg/dL, urine creatinine 22.8 mg/dL, 24-hour urine volume 2200 mL, 24-hour creatinine clearance 60 ml/min. Urine sodium concentration 105.6 mmol/L, serum sodium 114 mmol/L, sodium clearance: 1.41 ml/min. Fractional sodium excretion was 2.3%. Although the treatment was continued for 6 days, with the same dose of 420 mEq sodium given for each day, the serum sodium concentration reached to 115 mmol/L on day 6. (Totally, 2520 mEq of sodium was given for 6 days). Therefore, hyponatremia was thought to be due to urinary loss of sodium. The fractional sodium excretion of 2.3% supported this. All these findings suggested the diagnosis of renal salt wasting in this patient. We decided to give the patient fludrocortisone (Astonin H 0.1 mg) twice a day orally in addition to sodium chloride tablets (approximately 1.5 gram = 25-30 mmol). During the follow-up of the patient, the both fludrocortisone pills and salt tablets increased to 2 × 2, finally, when reached the level of sodium is above 130 mmol/L, salt tablets were stopped. One thing need to be noted here; hyponatremia did not improve unless giving fludrocortisone. But after this, although more sodium was given during sodium replacement, there was no increase in fractionated sodium excretion, on the contrary, it decreased. On day 14th, Fractional sodium elimination was 1.7%. Serum Na: 133 mmol/L. The patient was advised to take fludrocortisone tablets twice a day orally and was discharged from hospital on day 15th when serum sodium concentration was 138 mmol/L. If a patient with serum cortisol level below 4 mcg/dl have been evaluated as adrenal insufficiency regardless of ACTH level in sera.; additionally, hyperpigmentation and hyponatremia due to salt wasting through the kidneys led us to diagnose. The hyponatremia resolved only after added fludrocortisone. Conclusion However SCLC can give rise euvolemic hyponatremia producing ADH generally, besides, SCLC can cause adrenal insufficiency leading to serious hypovolemic hyponatremia. Diagnose is of crucial importance for correct treatment which can be only achieved by replacing the both sodium and fludrocortisone.

#1182 Arterial hypertension and chronic obstructive pulmonary disease—problems of choice of therapy

Abstract Background and Aims The development of hypertension in COPD is based on the early formation of endothelial dysfunction in the small and large circulatory circles, increased sympathetic activity with an imbalance in the synthesis of catecholamines, a violation of the role of the lungs in the metabolism of vasoactive substances, oxidative stress, chronic systemic inflammation, an imbalance in the renin-angiotensin-aldosterone system (RAAS). There are few studies confirming the role of RAAS components in the pathogenesis of cardiovascular changes in patients COPD. The activity of angiotensin converting enzyme (ACE) increases with hypoxia, which may play an important role in increasing the degree of systemic hypertension. An increase in the function of the RAAS is possible both under the direct influence of hypoxia and indirectly through activation of the sympathoadrenal system. To evaluate the efficacy and tolerability of the angiotensin II receptor antagonist valsartan (Nortivan) at a dose 80-160 mg per day in patients with hypertension of 1-2 degrees and COPD of stage II-IV. Method The study design is a local, open, incomparable study on the efficacy and safety of the drug Nortivan in patients with hypertension in combination with COPD. We examined 18 patients with stage II-IV in remission, suffering from grade I and II hypertension, determined in accordance with the generally accepted classification of blood pressure levels (VNOK, 2010). Results The criteria for exclusion from the study were the presence in patients of complications of hypertension, coronary heart disease, decompensated chronic pulmonary heart, endocrine diseases requiring drug correction, kidney pathology, chronic heart failure, oral steroid therapy. 10 days in the last 6 months before inclusion in the study, oncological diseases and any other conditions that could interfere with the interpretation and evaluation of the results of the study. Patients who had not previously received antihypertensive treatment were included in the study immediately, and the rest underwent a washing period for 2 weeks. Patients received Nortivan as antihypertensive therapy for 24 weeks. The effectiveness of therapy was controlled by daily monitoring blood pressure. The choice of quality criteria for the effectiveness of therapy parameters SMAD is associated with literature data and own observations on the prevalence of diurnal blood pressure profiles in patients with hypertension and COPD with no decrease or increase in blood pressure at night, when office blood pressure figures are to a lesser extent reflect the effectiveness of antihypertensive therapy. The initial dosage was 80 mg/day. With insufficient hypotensive effect, the dose of the drug was doubled at the 4th week of treatment. The basic COPD therapy did not change throughout the study period and included anticholinergic drugs (ipratropium bromide, tiotropium bromide), beta2-adrenomimetic (fe-noterol) or a combination thereof. Initially and after 24 weeks of treatment, a complete laboratory examination was performed: a clinical blood test, a biochemical blood test. The thickness of the intima-media complex of the carotid arteries and ECG was also studied. The criterion The safety of the therapy was assessed by the indicators of respiratory function, daily pulse oximetry. Conclusion The use of the drug Nortivan has shown high efficacy and safety in patients Grade I–II hypertension in combination with stage II-IV COPD. A statistically and clinically significant normalization of SMAD indicators with correction of pathological types of daily curves due to a decrease in the number of patients with an increase in or the absence of a decrease in blood pressure during the night period. The safety of using the drug in the clinical group with bronchial obstruction syndrome was confirmed by the dynamics of ventilation indicators according to spirometry and the results of daily pulse oximetry, which showed the absence of exacerbation of hypoxia during therapy.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. ClinicalTrials.gov, NCT02299414.

Using 30-day modified rankin scale score to predict 90-day score in patients with intracranial hemorrhage: Derivation and validation of prediction model.

Whether 30-day modified Rankin Scale (mRS) scores can predict 90-day scores is unclear. This study derived and validated a model to predict ordinal 90-day mRS score in an intracerebral hemorrhage (ICH) population using 30-day mRS values and routinely available baseline variables. Adults enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) trial between May 2011 and September 2015 with acute ICH, who were alive at 30 days and had mRS scores reported at both 30 and 90 days were included in this post-hoc analysis. A proportional odds regression model for predicting ordinal 90-day mRS scores was developed and internally validated using bootstrapping. Variables in the model included: mRS score at 30 days, age (years), hematoma volume (cm3), hematoma location (deep [basal ganglia, thalamus], lobar, or infratentorial), presence of intraventricular hemorrhage (IVH), baseline Glasgow Coma Scale (GCS) score, and National Institutes of Health Stroke Scale (NIHSS) score at randomization. We assessed model fit, calibration, discrimination, and agreement (ordinal, dichotomized functional independence), and EuroQol-5D ([EQ-5D] utility weighted) between predicted and observed 90-day mRS. A total of 898/1000 participants were included. Following bootstrap internal validation, our model (calibration slope = 0.967) had an optimism-corrected c-index of 0.884 (95% CI = 0.873-0.896) and R2 = 0.712 for 90-day mRS score. The weighted ĸ for agreement between observed and predicted ordinal 90-day mRS score was 0.811 (95% CI = 0.787-0.834). Agreement between observed and predicted functional independence (mRS score of 0-2) at 90 days was 74.3% (95% CI = 69.9-78.7%). The mean ± SD absolute difference between predicted and observed EQ-5D-weighted mRS score was negligible (0.005 ± 0.145). This tool allows practitioners and researchers to utilize clinically available information along with the mRS score 30 days after ICH to reliably predict the mRS score at 90 days.

Presence and development of diabetic retinopathy in 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy.

To evaluate the five-year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR-screening programme. Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013-2018. According to the worse eye at first screening, DR was classified (levels 0-4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication. At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five-year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63-1.89, and HR 2.04, 95% CI 1.73-2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10-1.47, and HR 2.80, 95% CI 2.23-3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05-1.36, and HR 1.98, 95% CI 1.53-2.57). In a study of all patients with type 1 diabetes from the Danish DR-screening programme, we identified duration of diabetes, systemic disease and use of anti-hypertensive treatment as consistent risk markers for incident and progressive DR.

Effects of renal denervation on the kidney: albuminuria, proteinuria, and renal function.

Renal denervation has attracted attention as a novel antihypertensive treatment for hypertensive patients who are poorly controlled by medicine. Clinical studies have shown the antihypertensive effects of renal denervation in patients with treatment-resistant hypertension. However, renal denervation potentially has other beneficial effects, such as improving glucose metabolism and cardioprotection beyond its antihypertensive effects. In this mini-review article, we summarize and discuss the effects of renal denervation on proteinuria, albuminuria, and renal function based on the recent findings of clinical studies, and review the renoprotective effects of renal denervation.

Predictive Score for Advanced Colorectal Neoplasia Based on Cardiovascular and Colorectal Cancer Risk Factors.

Background and Aims: Cardiovascular disease and colorectal cancer (CRC) are significant health problems and share some risk factors. The aim of our study was to develop and validate a predictive score for advanced colorectal neoplasia (CRN) based on risk factors for cardiovascular disease and CRC. Materials and Methods: A cross-sectional study comprising a derivation cohort and an external validation cohort of 1049 and 308 patients, respectively. A prediction score for advanced CRN (CRNAS: Colorectal Neoplasia Advanced Score) was developed from a logistic regression model, comprising sex, age, first-degree family history for CRC, systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, body mass index, diabetes, smoking, and antihypertensive treatment. Other cardiovascular risk scores (Framingham-Wilson, REGICOR, SCORE, and FRESCO) were also used to predict the risk of advanced CRN. The discriminatory capacity of each score was evaluated using the area under the curve (AUC). Results: CRN were found in 379 subjects from the derivation cohort (36%), including 228 patients (22%) with an advanced CRN. Male sex, age, diabetes, and smoking were identified as independent risk factors for advanced CRN. The newly created score (CRNAS) showed an AUC of 0.68 (95% CI: 0.64-0.73) for advanced CRN, which was better than cardiovascular risk scores (p < 0.001). In the validation cohort, the AUC of CRNAS for advanced CRN was 0.67 (95% CI: 0.57-0.76). Conclusions: The newly validated CRNAS has a better discriminatory capacity to predict advanced CRN than cardiovascular scores. It may be useful for selecting candidates for screening colonoscopy, especially in those with cardiovascular risk factors.

Plasma Biomarkers for Hypertension-Mediated Organ Damage Detection: A Narrative Review.

Hypertension (HT) is a disease that poses a serious threat to human health, mediating organ damage such as the cardiovascular (CV) system, kidneys, central nervous system (CNS), and retinae, ultimately increasing the risk of death due to damage to the entire vascular system. Thus, the widespread prevalence of hypertension brings enormous health problems and socioeconomic burdens worldwide. The goal of hypertension management is to prevent the risk of hypertension-mediated organ damage and excess mortality of cardiovascular diseases. To achieve this goal, hypertension guidelines recommend accurate monitoring of blood pressure and assessment of associated target organ damage. Early identification of organ damage mediated by hypertension is therefore crucial. Plasma biomarkers as a non-invasive test can help identify patients with organ damage mediated by hypertension who will benefit from antihypertensive treatment optimization and improved prognosis. In this review, we provide an overview of some currently available, under-researched, potential plasma biomarkers of organ damage mediated by hypertension, looking for biomarkers that can be detected by simple testing to identify hypertensive patients with organ damage, which is of great significance in clinical work. Natriuretic peptides (NPs) can be utilized as a traditional biomarker to detect hypertension-mediated organ damage, especially for heart failure. Nevertheless, we additionally may need to combine two or more plasma biomarkers to monitor organ damage in the early stages of hypertension.

Predicting hematoma expansion using machine learning: An exploratory analysis of the ATACH 2 trial

IntroductionHematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) is a key predictor of poor prognosis and potentially amenable to treatment. This study aimed to build a classification model to predict HE in patients with ICH using deep learning algorithms without using advanced radiological features. MethodsData from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) was utilized. Variables included in the models were chosen as per literature consensus on salient variables associated with HE. HE was defined as increase in either >33% or 6 mL in hematoma volume in the first 24 h. Multiple machine learning algorithms were employed using iterative feature selection and outcome balancing methods. 70% of patients were used for training and 30% for internal validation. We compared the ML models to a logistic regression model and calculated AUC, accuracy, sensitivity and specificity for the internal validation models respective models. ResultsAmong 1000 patients included in the ATACH-2 trial, 924 had the complete parameters which were included in the analytical cohort. The median [interquartile range (IQR)] initial hematoma volume was 9.93.mm3 [5.03–18.17] and 25.2% had HE. The best performing model across all feature selection groups and sampling cohorts was using an artificial neural network (ANN) for HE in the testing cohort with AUC 0.702 [95% CI, 0.631–0.774] with 8 hidden layer nodes The traditional logistic regression yielded AUC 0.658 [95% CI, 0.641–0.675]. All other models performed with less accuracy and lower AUC. Initial hematoma volume, time to initial CT head, and initial SBP emerged as most relevant variables across all best performing models. ConclusionWe developed multiple ML algorithms to predict HE with the ANN classifying the best without advanced radiographic features, although the AUC was only modestly better than other models. A larger, more heterogenous dataset is needed to further build and better generalize the models.