BP Levels Research Articles

TRPC6 participates in the development of blood pressure variability increase in sino-aortic denervated rats

Increased blood pressure variability (BPV) has been proved to be associated with cardiovascular morbidity and mortality. It is of great significance to elucidate the mechanism of BPV increase. The cation channel transient receptor potential canonical 6 (TRPC6) is involved in a series of cardiovascular disease. Our experiment aimed to explore the role of TRPC6 in the development of BPV increase. Sino-aortic denervation (SAD) operation was applied to establish the model of BPV increase in rats. The BPV was presented as the standard deviation to the mean of systolic or diastolic blood pressure every 1 h during 12h of the light period. SAD was performed in male Sprague Dawley (SD) rats at the age of 10weeks. At 8weeks after SAD operation, the hemodynamic parameters were determined non-invasively via a Rodent Blood Pressure Analysis System. The TRPC6 expressions in myocardial and thoracic aortic tissue was determined utilizing Western Blot, immunofluorescence and quantitative RT-PCR. The expression of TRPC3 was detected as well. To investigate whether TRPC6 was a causative factor of BPV increase in SAD rats, TRPC6 activator and inhibitor with three progressively increasing doses were intraperitoneally injected to the SAD rats. We found that SAD rats presented significant augmentation of systolic and diastolic BPV with no change of BP level and heart rate. The mRNA and protein expression levels of TRPC6 in myocardial and thoracic aortic tissue in SAD rats were substantially increased, but there was no obvious change in TRPC3 expression. The systolic and diastolic BPV increase were dose-dependently exacerbated after TRPC6 activation with GSK1702934A but were dose-dependently attenuated after TRPC6 inhibition with SAR7334. In Conclusion, the TRPC6 (but not TRPC3) expressions in myocardial and thoracic aortic tissue were substantially increased in SAD rats, and TRPC6 probably played an important role in the development of BPV elevation.

Sleep timing and hygiene practices of high bedtime procrastinators: a direct observational study.

Bedtime procrastination (BP) has been proven to be an important indicator of sleep insufficiency from a psychological perspective. However, the effect of BP on sleep patterns related to sleep deficiency remains unknown. This study aimed to investigate the characteristics of self-reported sleep timing and hygiene practices between high and low-moderate bedtime procrastinators. It also aimed to examine the relationship between these characteristics and high level of BP. A total of 391 Chinese college students were recruited for this study. Participants completed questionnaires on demographics, sleep timing variables, the Sleep Hygiene Practice Scale (SHPS) and the Bedtime Procrastination Scale (BPS). High bedtime procrastinators were more likely to have higher SHPS global and subdomain scores (Ps < 0.001). They also were more likely to exhibit later sleep onset, sleep offset and rise time on both weekdays and weekends (Ps < 0.01). The significant independent determinant factors of the prevalence of high BP were: SHPS total score [odds ratio (OR) = 1.05, P < 0.001], arousal-related behaviour (OR = 1.07, P = 0.007), sleep schedule and timing (OR = 1.12, P < 0.001) and sleep onset on weekdays (OR = 2.65, P < 0.001). High bedtime procrastinators showed maladaptive sleep-related variables, which mainly manifested as changes in arousal-related behaviour and sleep schedule and timing, as well as delays in sleep onset time on weekdays. The findings could help guide the formulation of appropriate interventions in primary health care.

Differences in patient and physician perspectives on pharmaceutical therapy and renal denervation for the management of hypertension.

Objective:To study patient and physician attitudes to pharmaceutical therapy and renal denervation for the management of hypertension.Methods:Data were analyzed from 19 market research studies in Western Europe and the United States conducted between 2010 and 2019 to obtain quantitative and qualitative perspectives. The analysis incorporated insights from 2768 patients and the experiences of 1902 physicians either actively performing or interested to perform device procedures, or hypertension specialists who would refer patients for a device-based intervention.Results:Referring cardiologists and proceduralists were more likely to recommend the renal denervation procedure to patients with higher BP levels and a greater number of antihypertensive medications. Physicians perceived patient reluctance towards a procedure as an important obstacle to recommending renal denervation as a treatment option for uncontrolled hypertension. Patient interest in the renal denervation procedure did not correlate with BP severity (P = NS), and the highest preference for the procedure was in patients diagnosed with hypertension but not receiving treatment (P < 0.001). Patients who perceived high BP as a major problem (P = 0.029) and those who experienced side effects attributed to their BP medications (P = 0.006) had a higher preference for renal denervation.Conclusion:Patients with hypertension often regard the choice of renal denervation to lower BP differently from physicians. A considerable proportion of hypertensive patients, especially those not taking medications, may prefer a device-based approach to reduce their BP.

Kinetic modeling of glucose central metabolism in hepatocytes and hepatoma cells

BackgroundKinetic modeling and control analysis of a metabolic pathway may identify the steps with the highest control in tumor cells, and low control in normal cells, which can be proposed as the best therapeutic targets. MethodsEnzyme kinetic characterization, pathway kinetic modeling and control analysis of the glucose central metabolism were carried out in rat (hepatoma AS-30D) and human (cervix HeLa) cancer cells and normal rat hepatocytes. ResultsThe glycogen metabolism enzymes in AS-30D, HeLa cells and hepatocytes showed similar kinetic properties, except for higher AS-30D glycogen phosphorylase (GP) sensitivity to AMP. Pathway modeling indicated that fluxes of glycogen degradation and PPP were mainly controlled by GP and NADPH consumption, respectively, in both hepatocytes and cancer cells. Likewise, hexose-6-phosphate isomerase (HPI) and phosphoglucomutase (PGM) exerted significant control on glycolysis and glycogen synthesis fluxes in cancer cells but not in hepatocytes. Modeling also indicated that glycolytic and glycogen synthesis fluxes could be strongly decreased when HPI and PGM were simultaneously inhibited in AS-30D cells but not in hepatocytes. Experimental assessment of these predictions showed that both the glycolytic and glycogen synthesis fluxes of AS-30D cells, but not of hepatocytes, were inhibited by oxamate, by inducing increased Fru1,6BP levels, a competitive inhibitor of HPI and PGM. ConclusionHPI and PGM seem suitable targets for decreasing glycolytic and glycogen synthesis fluxes in AS-30D cells but not in hepatocytes. General significanceThe present study identified new therapeutic targets within glucose central metabolism in the analyzed cancer cells, with no effects on non-cancer cells.

Time And Dose Of Blood Pressure Medication Improves Hidden Hypertension Risk In A Firefighter

Most firefighters (FF) are unaware of their BP levels, which increases their risk of undiagnosed hypertension. According to a recent study, BP medication taken at bedtime lowers levels more effectively and leads to a 66% decrease in the risk of fatal cardiac incidents. Using ambulatory BP (ABP) monitoring to measure BP over time is a recommended way to assess risk. PURPOSE: To provide evidence that time and dosage of BP medication can improve hypertension risk in FF. METHODS: We included 43 FF in an ongoing clinical trial. FF wore an ABP cuff for a period, and the overall average BP, daytime BP and nighttime BP levels were examined. FF also came to the lab for a clinical fasted visit including BP, body fat, and vascular health measures. For this sub-analysis, we report data from 1 FF who was found to have nocturnal hypertension and morning BP surge. RESULTS: Overall the entire group of FF were hypertensive with clinic BP of 128.7 ± 1.7/ 81.8 ± 1.2 mmHg, had high central BP measured by SphygmoCor® XCEL (121.8 ± 2.7/ 84 ± 1.5 mmHg), and had high average SBP measured by ABP (130.9 ± 1.5 mmHg). We identified several FF with nocturnal hypertension and high morning BP surge levels, and here we report on data on one. He was 53 yr old, weighed 226 lbs, had 36.1% body fat, was an uncontrolled hypertensive (140.5/84.5 mmHg), and had high central BP levels (134/81 mmHg). During the initial ABP monitoring, his daytime BP was 160.2/86.9 and nighttime BP was 178.9/87.1 mmHg. His BP rose in the morning to 203/104 mmHg and remained that level for 2hrs. The FF self-reported feeling headaches and a ‘rushing sensation’ during fire calls, so he took his ABP data to a clinician. Initially, he was prescribed BP med in AM. The doctor increased dosage and switched to nighttime medication. During follow-up ABP monitoring, the FF’s BP was much more controlled. His average daytime BP was 145.1/82.6, nighttime BP was 114.8/66.2, and morning BP was only 125/69 mmHg. CONCLUSION: With this case-study data from one FF in a larger clinical trial, we confirmed that timing and dosage of medication leads to improved BP levels. This further confirms that overall health awareness in FF is important. Fire chiefs and the firehouse medical director should encourage and increase BP monitoring. This one example proves to be a valuable anecdote when we enter firehouses and discuss our clinical trial.

Firefighters With More Service Have Smaller Blood Pressure Surge When The Pager Sounds

Cardiac incidents cause over 50% of LODD in firefighters (FF) and may be related to their BP responses. Also, years of service may affect FF stress and depression levels and impair overall health. Using ambulatory BP (ABP) monitoring to quantify the BP surge with alarm is a novel way to assess risk, and preliminary data showed that newer FF have higher BP surge. PURPOSE: To compare changes in health between FF with <10yr service (FF-10) and FF with >10yr service (FF+10) after a 6-wk Mediterranean diet & circuit training program. METHODS: We included 21 FF who completed a 6-wk intervention. Pre- and post-intervention testing included ABP monitoring with pager activation, a fasted clinical appt, and fitness testing. Participants wore the ABP cuff for 12-hrs, during which they were paged by a pager app (OnPage) or by emergency service dispatch. When the pager sounded, they were instructed to force an ABP reading to assess the BP surge. Average BP levels and surges were determined. Fasted visit included BP, body fat, lipid panel, and vascular health measures. Fitness test included a treadmill VO2peak and a battery of other fitness tests. Participants also completed a health history form and the DASS-21 questionnaire assessing stress, anxiety, and depression. RESULTS: FF+10 (N=12, 45.7 ± 3yrs) had worse health and lower BP surges, but larger improvements with intervention compared to FF-10 (N=9, 36.8 ± 6.2yrs), P<0.05 for differences. FF+10 had lower HDL levels (38.3 ± 2.2 vs 57.9 ± 9.7 mg/dl), were heavier (213.1 ± 8.6 vs 205.1 ± 8.6 lbs), had higher average SBP (136.6 ± 4.8 vs 126.9 ± 3.6 mmHg) and DBP (83.2 ± 2.8 vs 75.7 ± 2.8 mmHg) levels, higher pre-alarm and post-alarm BP, but had a smaller surge in SBP (11.6 ± 3.2 vs 15.0 ± 3.3 mmHg) and DBP (4.1 ± 2.7 vs 7.3 ± 1.7 mmHg) when the pager sounded. FF+10 also had worse overall psychometric scores: higher DASS-21 11.2 ± 5.3 vs 7.6 ± 1.3; depression 3.4 ± 1.3 vs 1.4 ± 0.3; and stress 5.4 ± 1.7 vs 3.3 ± 0.5; but similar anxiety scores 2.4 ± 1.0 vs 3.0 ± 0.9. With intervention, in FF+10 we found that BP lowered, fitness improved, and psychosocial constructs improved. CONCLUSION: With this subset of baseline data, we show that FF+10 have smaller BP surge, worse CV health, stress, and depression levels, but larger improvements with intervention compared to FF-10. Data confirms the importance of wellness programs for FF.

Dietary Patterns and Their Association with CVD Risk Factors among Bangladeshi Adults: A Cross-Sectional Study

Purpose The objective of this study was to evaluate the association between dietary patterns and CVD risk factors among adults. Methods Demographic data, knowledge, attitude, practices toward CVD related data, dietary data, and some biochemical data were collected from 250 participants at Coronary Care Unit of Jashore 250 bedded Sadar Hospital in Jashore district. A multinomial logit regression method was used to examine the association between LDL and TG levels with the dietary diversity of CVD risk patients. Results According to the BMI, most of the respondents were overweight. The respondent’s practice level was poor than their knowledge and attitude level toward CVD. A positive correlation was found among the respondents’ knowledge, attitude, and practice. Most of the CVD patient’s troponin value and BP level were found higher than the acceptable limit. Along with their lipid profile level was not good. Most of them were in borderline risk condition of CVD and some had high risk. The patients who consumed a higher amount of red meat, egg, cheese, fast food, soft drinks, and salty snacks had more probability of increasing LDL and TG level in blood which was the major risk factors of CVD than the patients who consumed fish, chicken, pulse, nuts, fruits, and vegetables in their diet regularly. Conclusion This study suggests that the consumption of fatty foods, fast foods, and soft drinks leads to the probability of increasing LDL and TG levels in CVD risk patients.

P0790RISK OF CARDIOVASCULAR DISEASE AND CHRONIC KIDNEY DISEASE ACCORDING TO BLOOD PRESSURE CATEGORIES IN DIABETIC PATIENTS : A POPULATION-BASED STUDY

Abstract Background and Aims American College of Cardiology/American Heart Association (ACC/AHA) guidelines and cardiovascular disease (CVD) and chronic kidney disease (CKD) in diabetes patients remain unclear. We aimed to examine the effects of BP categories defined by the 2017 ACC/AHA guidelines in diabetes patients on the risk of CVD and CKD. Method In this population-based cohort study we analyzed data from the National Health Information Database in Korea during 2009-2017. The BP categories were defined as per the 2017 ACC/AHA guidelines: level 1 (systolic &amp;lt;120 mmHg and diastolic &amp;lt;80 mmHg), level 2 (systolic 120-129 mmHg and diastolic &amp;lt;80 mmHg), level 3 (systolic 130-139 mmHg or diastolic 80-89 mmHg), and level 4 (systolic ≥140 mmHg or diastolic ≥90 mmHg). We obtained the risk of CVD, CKD, cerebrovascular disease and CVD mortality. Results Overall, 490,352 diabetes patients (men 313,752 [64·0%], women 176,599 [36·0%]) were included in the analysis. Over a mean follow-up of 5 years, 6,508 CVD events occurred. Compared to people with BP levels 1, the adjusted hazard ratios (HRs) for CVD in people with BP levels 2, 3, and 4 were 1·07 (95% confidence interval [CI], 0·98-1·16), 1·12 (95% CI, 1·04-1·20) and 1·17 (95% CI, 1·08-1·26), respectively. There were also increased risks of CKD [1·18 (95% CI, 1·12-1·24) and 1·22 (95% CI, 1·15-1·29)], cerebrovascular disease [1·21 (95% CI, 1·14-1·29) and 1·52 (95% CI, 1·42-1·63)], and CVD mortality [1·31 (95% CI, 1·09-1·56) and 1·91 (95% CI, 1·58-2·32)] among subjects with BP levels 3 and 4 compared with those with BP level 1. Moreover, among people not taking antihypertensive medications, there were higher risks of CVD, CKD, cerebrovascular disease, and CVD mortality in those with BP levels 3 and 4 than in those with BP level 1. The risks of CVD, CKD, cerebrovascular disease, and CVD mortality significantly increased in patients with a systolic BP of 130 mmHg and diastolic BP of 80 mmHg. These findings provide evidence supporting the 2017 ACC/AHA guidelines for BP targets in diabetes patients. Conclusion The risks of CVD, CKD, cerebrovascular disease, and CVD mortality significantly increased in patients with a systolic BP of 130 mmHg and diastolic BP of 80 mmHg. These findings provide evidence supporting the 2017 ACC/AHA guidelines for BP targets in diabetes patients.

Smoking and hypertension: what is behind the mask?

Smoking and hypertension: what is behind the mask?

1180-P: Better Care Strategies Are Necessary to Address Poor Medication Adherence

Background: As part of a clinical decision support (CDS) and pharmacist outreach interventional study to improve medication adherence, we analyzed rates and clinical implications of poor adherence for diabetes (DM), hypertension (HTN) and lipid control. Methods: In two high performing care delivery systems in MN, 28 clinics were randomized to an adherence CDS intervention or control. The CDS uses web-based algorithms to assess clinical data and objectively capture poor adherence using an Epic based measurement of Proportion of Days Covered (ePDC) calculated using SureScripts dispense data with a moderate or high confidence rating. For 16 weeks in 2019, the CDS ran silently in all primary care encounters of patients age 18-75 to determine how many patients qualified for study eligibility using the following criteria: 1.DM cohort: A1c ≥8% with a non-insulin glycemic medication ePDC &amp;lt; 80%. 2. HTN cohort: BP ≥140/90 on two separate consecutive dates with a BP medication ePDC &amp;lt; 80%. 3. Lipid cohort: ACC/AHA criteria for statin use, on a statin with ePDC &amp;lt; 80%, excluding for LDL &amp;lt; 70 mg/dl. Results: Of 142,879 patients, 138,252 remained after excluding for cancer, pregnancy, hospice or nursing home. A non-insulin DM medication was identified in 15,546 (11%). Of these, 3890 (25%) had A1C ≥ 8%, and of these 1467 (59%) had poor adherence. Among the DM cohort, the mean A1C was 9.6% and 30% had A1C ≥10%. Of patients identified with DM in the HTN cohort (494/1711, 29%), 60% had a systolic blood pressure ≥ 150 mm Hg. Of patients identified with DM in the lipid cohort (2298/4564, 50%), 19% had an LDL ≥130 mg/dl. Conclusion: Over 14 weeks, large numbers of DM patients were identified at primary care encounters with difficulty achieving A1C, BP and lipid goals in association with poor medication adherence, which was often unrecognized. Based on extremely high A1C, BP and LDL levels in these patients, there is a tremendous clinical opportunity to identify and address poor adherence using CDS and/or pharmacist care team involvement. Disclosure J.M. Sperl-Hillen: None. J.P. Anderson: None. J. Haapala: None. L. Chumba: None. H. Ekstrom: None. D. Appana: None. M.B. DeSilva: None. P.J. O’Connor: None.

P1781CONVERSION TO SIROLIMUS IN ADVANCED STAGES OF CHRONIC ALLOGRAFT NEPHROPATHY. A RANDOMIZED CLINICAL TRIAL

Abstract Background and Aims Some studies have shown that proteinuria more than 800 mg per day and glomerular filtration rate (GFR) less than 40 ml/min are the most important relative contraindications for mTOR inhibitors prescription. There is no pathophysiologic reason to put aside mTOR inhibitors in more advanced stages of chronic allograft nephropathy(CAN). To clarify the safety of conversion to mTOR inhibitors in more advanced stages of CAN we conduct a randomized clinical trial Method Among 1911 renal transplant recipients which was performed from May 1989 to May 2016, patients (pts) with CAN included to the study. CAN was defined by pathology results and rule out of other causes of renal dysfunction and GFR less than 60 ml/min. pts with recent acute rejection, chronic Ab mediated rejection, active viral infection, malignancy, advanced cardiac, liver and respiratory diseases, obstructive uropathy and non-adherence were excluded from the study. After exclusion there were 211 pts with CAN. Among CAN pts 112 pts have GFR less than 40 ml/min. These patients were assigned in two group randomly. Group 1 continued their immunosuppression which consists of mycophenolate mofetil/myfortic, Cyclosporin A /Tacrolimus and prednisolone. Group B which received Sirolimus 2 mg daily instead of CyclosporinA / tacrolimus. All pts followed for 18 months. allograft function and pts morbidity and mortality were monitored every two months. results were recorded in clinic sheets and were analyzed using SPss version 22 Results G1 consist of 53 and G2 59 pts. There were no differences in two group in respect to sex (M/F was 0.89 and 0.84 in G1 and G2 respectively), and age (mean age was 41 6 9.5 and 43 6 8.23 in G1 and G2 respectively). there were no differences in admission rate for medical reasons (0.43 and 0.39 admission per pts per year in G1 and G2 respectively p=0.23). There was no difference between two group in respect to cardiovascular events (0.23 and 0.27 events per pts per year in G1 and G2 respectively p=0.31). The average trough level of SRL was 8.38± 3.12 ng/mL at 18 months. At 18 months, the incidence of acute rejection was not higher in G2 (21% vs. 18.8 %, p = 0.21) and renal function was superior in patients converted to SRL (eGFR 32.3 vs. 23.4 mL/min/ 1.73 m2, p = 0.019) compared to those maintained on CsA/TAC. There were no significant differences in pts survival (one death in each group) Graft loss was higher in G1( 5 versus 2 at 18 months p= 0.014). there were no significant differences in respect to liver, respiratory, GI, hematologic and infectious complications. pts in G2 group had lower BP and uric acid levels. Conclusion Conversion to mTOR inhibitors in more advanced stages of CAN is safe and has beneficial effect on renal allograft function with no more side effect.

Hypertension in Workers: The Role of Physical Activity and its Different Dimensions.

ResumoFundamento A atividade física, em diferentes dimensões (ocupacional, doméstica e de lazer), pode ter papel relevante sobre a hipertensão arterial (HA). Praticar atividade física apenas no lazer, ou isoladamente nas outras dimensões, pode ser insuficiente para o controle efetivo da HA.Objetivo Analisar o efeito isolado e cumulativo das dimensões da atividade física sobre a ocorrência de hipertensão arterial em trabalhadores.Métodos Estudo transversal com 1.070 trabalhadores de Limpeza Urbana e Indústria de Calçados, na Bahia, utilizando questionário aplicado por entrevistador acerca de aspectos sociodemográficos, ocupacionais, de estilo de vida e morbidade hipertensiva.Foram medidos peso, altura, circunferência abdominal e pressão arterial. Caso de HA: pressão arterial sistólica ≥140 ou diastólica ≥90, ou tratamento regular de Hipertensão. Foram investigadas as dimensões ocupacional, doméstica e de lazer da atividade física. Realizou-se análise multivariada com Regressão de Cox para estudos transversais.Resultados A prevalência de HA foi de 24%, sendo 37% dentre pacientes com idades entre 35 e 44 anos, e 51% entre 45 e 54 anos. O modelo multivariado evidenciou que ativos em uma dimensão ou em nenhuma tiveram 62% mais HA, e um valor 25% mais elevado de HA foi observado dentre aqueles trabalhadores ativos em duas das três dimensões, na comparação com os ativos nas três dimensões. Sexo masculino, maior idade (> 31 anos) e excesso de peso se associaram à HA, com razões de prevalência de 1,62, 2,10 e 2,26, respectivamente.Conclusões Verificou-se efeito cumulativo das dimensões da atividade física sobre a ocorrência de HA. Classificar sujeitos ativos no trabalho ou no ambiente doméstico como inativos ao se basear apenas na dimensão do lazer pode implicar em erro metodológico. (Arq Bras Cardiol. 2020; 114(5):755-761)

PFKFB2 regulates glycolysis and proliferation in pancreatic cancer cells.

Tumor cells increase glucose metabolism through glycolysis and pentose phosphate pathways to meet the bioenergetic and biosynthetic demands of rapid cell proliferation. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) are key regulators of glucose metabolism via their synthesis of fructose-2,6-bisphosphate (F2,6BP), a potent activator of glycolysis. Previous studies have reported the co-expression of PFKFB isozymes, as well as the mRNA splice variants of particular PFKFB isozymes, suggesting non-redundant functions. Majority of the evidence demonstrating a requirement for PFKFB activity in increased glycolysis and oncogenic properties in tumor cells comes from studies on PFKFB3 and PFKFB4 isozymes. In this study, we show that the PFKFB2 isozyme is expressed in tumor cell lines of various origin, overexpressed and localizes to the nucleus in pancreatic adenocarcinoma, relative to normal pancreatic tissue. We then demonstrate the differential intracellular localization of two PFKFB2 mRNA splice variants and that, when ectopically expressed, cytoplasmically localized mRNA splice variant causes a greater increase in F2,6BP which coincides with an increased glucose uptake, as compared with the mRNA splice variant localizing to the nucleus. We then show that PFKFB2 expression is required for steady-state F2,6BP levels, glycolytic activity, and proliferation of pancreatic adenocarcinoma cells. In conclusion, this study may provide a rationale for detailed investigation of PFKFB2's requirement for the glycolytic and oncogenic phenotype of pancreatic adenocarcinoma cells.

Influence of Genetic Admixture Components on CYP3A5*3 Allele-Associated Hypertension in Amerindian Populations From Northwest Mexico.

CYP3A5 metabolizes endogenous substrates and ~30% of prescription drugs. The CYP3A5 gene contains an active CYP3A5*1 allele, and a non-functional version, the CYP3A5*3 (rs776746), with consequences for drug therapeutic responses and side effects. Both CYP3A5*1 and *3 have been associated with hypertension. The frequency of CYP3A5*3 varies between populations of different ancestries, with Europeans having the highest allele frequency (> 90%). Given the importance of CYP3A5*3 in drug response and hypertension development, the aim of the present study was to evaluate the frequency of this polymorphism and its association with hypertension in vulnerable indigenous populations in Mexico. A total of 372 subjects were recruited from eight ethnic groups in Northwest Mexico. Systolic (SBP), diastolic (DBP), and median (MBP) blood pressures as well as body mass index (BMI) were measured. Ancestry was evaluated through STR analysis, and the CYP3A5*1/*3 polymorphisms were identified using real-time PCR with TaqMan® probes. Higher frequencies of CYP3A5*1 and *3 were observed in groups with higher (>90%) and lower (<90%) Amerindian ancestry, respectively. The CYP3A5*3/*3 genotype was more frequent in indigenous women with higher SBP and DBP values. On the other hand, the *1 allele showed a protective effect against both high SBP (OR, 0.38; 95% CI, 0.17–0.83, p = 0.001) and DBP (OR 0.38, 95% CI 0.18–0.81, p = 0.007) in women. This association remained significant after adjusting for BMI and age for diastolic (OR, 0.38; 95% CI, 0.17–0.84, p = 0.011) and systolic BP (OR, 0.33; 95% CI, 0.15–0.76, p = 0.005) BP levels in women. Thus, the frequency of CYP3A5*3 varies between groups and seems to depend on ancestry, and CYP3A5*1 decreases the risk of hypertension in Mexican indigenous women. This population analysis of CYP3A5*1/*3 has profound implications not only for the susceptibility to diseases, such as hypertension, but also for safer drug administration regimens, assuring better therapeutic responses and fewer side effects.

SUN-168 Case Series of ACTH-Secreting Pheochromocytoma: Diagnosis and Management

INTROACTH-secreting pheochromocytoma is rare, posing challenges in diagnosis and management. Here we report two cases with different presentations and pre-operative approaches.CASES Patient 1 A 59 yo female who presented for basal cell carcinoma resection experienced hypertensive crisis intra-op and NSTEMI due to stress cardiomyopathy. The patient reported spells of palpitations, diaphoresis, tremors and pallor since 2015. She had elevated plasma metanephrine (M) 19.4 (0-0.49nmol/L), normetanephrine (NM) 24.7 (0-0.89nmol/L), 24-hour urine M 18711 (30-180mcg) and NM 11897 (128-484mcg). Imaging demonstrated a 5.6 x 5.5 x 5.8cm left adrenal mass. After pre-operative alpha and beta blockade, patient underwent left adrenalectomy.Pre-op 24-hour urine cortisol was checked as part of secondary HTN evaluation and found to be elevated at 219 (3.5-45mcg). She did not have any features of Cushing’s and this was initially felt to be an appropriate stress response. Due to persistent post-op hypotension and a low 10PM random cortisol level of 3.4mcg/dL, which was inappropriate given patient’s clinical status, hydrocortisone was started with subsequent hemodynamic improvement. Our suspicion was that she had an ACTH-secreting pheochromocytoma, which would have resulted in hypercortisolism pre-op, and secondary AI post-op. Pathology report later confirmed ectopic ACTH production with 25% cells positive with immunostaining. Patient 2 A 48 yo female was admitted for hypertensive urgency with symptoms of palpitations, facial and abdominal swelling, easy bruising and proximal muscle weakness. Her labs showed elevated 24-hour urine epinephrine 115 (0-20mcg), norepinephrine 366 (0-135mcg), plasma M 288 (0-62pg/mL) and NM 475 (0-145pg/mL), and an AM cortisol was 47.9mcg/dL. Aldosterone and renin levels were <1ng/dL and 0.775ng/mL/hr. Imaging revealed 3.4 x 3.1cm right adrenal mass with portal venous phase of 53 HU and no washout. AM cortisol level post 1mg dexamethasone was 62.6mcg/dL with an ACTH level of 222pg/mL. An ACTH-producing pheochromocytoma was suspected. Despite progressive uptitration of alpha and beta blockade, her BP remained poorly controlled. Her blood glucose also increased to 300s range. Ketoconazole 400mg BID was subsequently added to the regimen with rapid and marked improvement in BP and glycemic control. She underwent right adrenalectomy. Post-op plasma M, NM and ACTH were <0.20nmol/L, 0.36nmol/L and <5pg/mL.DISCUSSIONWithin the past 6 months, we have seen 2 cases of ACTH-secreting pheochromocytoma with different clinical symptoms and pre-op courses. Ectopic ACTH secretion may not cause classic Cushingoid features as in patient 1. Failure to recognize ectopic ACTH pre-op can lead to post-op complications such as AI. Patient 2 demonstrates that treatment of the hypercortisolemia may be necessary in order to adequately control BP and glucose levels prior to surgery.

A practical approach to switch from a multiple pill therapeutic strategy to a polypill-based strategy for cardiovascular prevention in patients with hypertension.

: Pharmacological treatment recommended by guidelines for very high-risk patients with established cardiovascular disease (CVD) includes lipid-lowering drugs, antihypertensive agents and antiplatelet therapy. Depending on the associated comorbidities, this baseline regimen has to be complemented with other drugs. Therefore, the number of pills to be taken is usually high and adherence to these multiple pill therapeutic regimens and long-term persistence on treatment is low, being the main factor for insufficient control of cardiovascular risk factors. The CNIC (Centro Nacional de Investigaciones Cardiovasculares, Ministerio de Ciencia e Innovación, España) polypill is the only polypill containing low-dose aspirin approved by the EMA and marketed in Europe, and has demonstrated to improve adherence. For this reason, guidelines recommend its use for secondary prevention of CVD, and also for primary prevention of cardiovascular events in patients with multiple cardiovascular risk factors and advanced atherosclerotic process at high risk of thrombosis and low risk of bleeding. This article pretends to simplify the steps that clinicians may follow to switch from any baseline regimen to the polypill with the use of several algorithms and tables showing the equivalent effective daily doses of different angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and statins to facilitate switching, as well as the steps to be followed depending of the initial levels of BP and LDL-cholesterol values to achieve BP and lipid control with the association to the polypill of other BP-lowering or lipid-lowering drugs whenever needed.

Therapeutic approaches to the Rational Use of trip-le combination therapy with a fixed combination of amlodipine, indapamide and perindopril arginine (TRIPLE COMBINATION) in patients with hypertension who do not control blood pressure on conventional treatment. (Description and main results of the TRIO program)

Aim To study tactics of outpatient physicians in choosing the treatment when the previous double antihypertensive therapy (AHT) fails and to analyze the effectivity of an amlodipine/indapamide/perindopril arginine triple combination (TC).Material and methods The program included 1252 patients with arterial hypertension (AH); the TC group consisted of 992 (79.23 %) patients (38.3 % males; age, 61.6 [55.0; 67.9]); the control group included 260 (20.77 %) patients (37.7 % males; age, 60.6 [53.3; 67.4]). The main inclusion criteria were essential AH, age 18-79 years, insufficient response to previous AHT (clinical systolic blood pressure (SBP) &gt;140-179 mm Hg). The study duration was three months. The following parameters were evaluated: dynamics of clinical and ambulatory BP (BP self-monitoring (BPSM); frequency of achieving the first goal of &lt;140 / 90 mm Hg and the goal of &lt;130 / 80 mm Hg); and changes in glomerular filtration rate (GFR) and quality of life (QoL). Responses to TC were analyzed in groups with different ranges of increased baseline SBP in patients with AH and diabetes mellitus (DM)/impaired glucose tolerance (IGT), overweight or obesity, and chronic kidney disease (CKD, reduced estimated GFR (eGFR &lt;60 ml/min/1.73 m2). Safety was evaluated based on records of adverse events (AEs).Results The TC group had a more severe condition at baseline by clinical parameters and history and had higher baseline BP, which made difficult the intergroup comparison. Nevertheless at three months, the decrease in clinical SBP was more pronounced in the TC group (from 162.1 to 126.8 mm Hg, Δ=35.7 mm Hg) than in the control group (from 157.8 to 128.4 mm Hg, Δ=29.4 mm Hg). 87.8% of patients in the TC group and 81.9 % (р=0.012) in the control group achieved the first BP goal of &lt;140 / 90 mm Hg; 34.3% and 28.2% of patients, respectively, achieved the BP goal of &lt;130 / 80 mm Hg (р=0.055). The more effective SBP control in the TC group was associated with a pronounced BP decrease with higher BP values at baseline, which was also confirmed by an analysis in subgroups with SBP 140-160, 160-180, and &gt;180 mm Hg. The TC treatment was associated with a pronounced antihypertensive effect with respect of BPSM values, improved QoL, and renal function. Significant decreases in BP and achievement of BP goals by a vast majority of patients receiving TC were also observed in subgroups with DM or IGT, overweight and/or obesity, and CKD. AEs were observed during the treatment only in 8 patients (0.64 %), which confirmed good tolerability and high safety of the therapy.Conclusion The study results demonstrated a therapeutic effect of the amlodipine/indapamide/perindopril arginine fixed-dose combination (Triplixam®). This effect was evident as control of clinical BP with any baseline BP level, including different ranges of increased SBP, in AH combined with DM, IGT, obesity, and CKD, which offers advantages over a subjective choice of AHT. TC improved BPSM values, QoL indexes, provided nephroprotection, and was well tolerated.

Prognostic importance of visit-to-visit blood pressure variability for micro- and macrovascular outcomes in patients with type 2 diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study

BackgroundThe prognostic importance of an increased visit-to-visit blood pressure variability (BP-VVV) for the future development of micro- and macrovascular complications in type 2 diabetes has been scarcely investigated and is largely unsettled. We aimed to evaluate it in a prospective long-term follow-up study with 632 individuals with type 2 diabetes.MethodsBP-VVV parameters (systolic and diastolic standard deviations [SD] and variation coefficients) were measured during the first 24-months. Multivariate Cox analysis, adjusted for risk factors and mean BP levels, examined the associations between BP-VVV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications (total cardiovascular events [CVEs], major adverse CVEs [MACE] and cardiovascular and all-cause mortality). Improvement in risk discrimination was assessed by the C-statistic and integrated discrimination improvement (IDI) index.ResultsOver a median follow-up of 11.3 years, 162 patients had a CVE (132 MACE), and 212 patients died (95 from cardiovascular diseases); 153 newly-developed or worsened diabetic retinopathy, 193 achieved the renal composite outcome (121 newly-developed microalbuminuria and 95 deteriorated renal function), and 171 newly-developed or worsened peripheral neuropathy. Systolic BP-VVV was an independent predictor of MACE (hazard ratio: 1.25, 95% CI 1.03–1.51 for a 1-SD increase in 24-month SD), but not of total CVEs, cardiovascular and all-cause mortality, and of any microvascular outcome. However, no BP-VVV parameter significantly improved cardiovascular risk discrimination (increase in C-statistic 0.001, relative IDI 0.9%).ConclusionsSystolic BP-VVV was an independent predictor of MACE, but it did not improve cardiovascular risk stratification. The goal of anti-hypertensive treatment in patients with type 2 diabetes shall remain in controlling mean BP levels, not on decreasing their visit-to-visit variability.

Therapeutic Inhibition of Sphingosine Kinase SphK2 lowers Blood Pressure Levels in an Experimental Model of Hypertension by Reducing CD4+ T‐cell Responses

Hypertension is a major cause of premature death in the world and the primary contributor to target organ damage. Although many therapeutic strategies to combat hypertension and its comorbidities exist, none of the current anti‐hypertension medications target the immune system, which evolved as key player in the pathogenesis of hypertension. During hypertension, the activation of the immune system links to alterations in sphingosine‐1‐phosphate (S1P) signaling and specifically, to sphingosine kinase 2 (SphK2)‐mediated immune cell chemotaxis. Our previous findings revealed a protection from the development of hypertension in SphK2 knockout mice. In this study, we explored the efficacy of pharmacological SphK2 inhibition to lowering elevated blood pressure and immune activation during angiotensin II‐induced hypertension in mice.In a murine model of hypertension where we treated mice with the SphK2 inhibitor ABC294640 or saline for two weeks, we assessed BP levels using tail cuff plethysmography, immune cell populations using flow cytometry, and circulating S1P levels using mass spectrometry. Using decision trees as a method of supervised machine learning, we set out to identify a sequential set of rules on measurement outcomes, which predict a successful reduction of BP.Pharmacological SphK2 inhibition significantly lowered BP levels, without affecting plasma S1P levels. Notwithstanding its incapacity to lower S1P plasma levels, pharmacological SphK2 inhibition drastically affected T‐cell populations in the blood as evidenced by significantly reduced overall circulating CD4+ T‐cells compared to placebo‐treated hypertensive mice. Besides dampening T‐cell responses typically associated to hypertension (i.e., TH17 and TH1 responses), pharmacological SphK2 inhibition resulted in marked increases of the IL4+TH2 subset. Interestingly, the rules learned by a decision tree identify CD4+ T‐cells as critical modulators for BP responses. Thus, therapeutic administration of CD4 blocking antibody diminished the number of circulating CD4+ T‐cells and significantly lowered elevated blood pressure levels.Our results provide profound evidence that the SphK2‐S1P signaling axis regulates systemic immune cell homeostasis and T‐cell phenotype changes important to blood pressure regulation. Taken together, our work identified first evidence for SphK2 inhibitors as successful immune‐based therapy in hypertension.Support or Funding InformationThis research was supported by the Swedish Research Council (VR 2017‐01243), the Ake Wibergs Stiftelse (M17‐0031), and the Knut &amp; Alice Wallenberg Foundation.

Calcium and Phosphate Levels are Among Other Factors Associated with Metabolic Syndrome in Patients with Normal Weight.

Background and PurposeWe aimed to assess the association between calcium and phosphorous and metabolic syndrome (MetS) in normal-weight individuals.Patients and MethodsThe study sample comprised 460 normal-weight (body mass index <25kg/m2) adults aged 18–35 years. The diagnosis of MetS was based on the presence of at least two of the following: 1) systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥85 mmHg, 2) triglycerides (TG) >150 mg/dl, 3) high-density lipoprotein cholesterol (HDL-C) <1 mmol/in men and <1.2 mmol/l in women, 4) total cholesterol (TC) >5.2 mmol/l, and 5) fasting glucose (FBG) >5.55 mmol/l.ResultsPatients with MetS were more often male and slightly older and they had a higher body mass index (BMI) and waist circumference. By definition, patients with MetS had higher levels of BP, GLC, glycated hemoglobin A1c, TC, low-density lipoprotein cholesterol (LDL-C), TG, and apolipoprotein B but significantly lower concentrations of HDL-C and apolipoprotein A. Moreover, subjects with MetS had higher activity of the liver enzymes alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase (GGTP). Higher concentrations of uric acid, creatinine and albumin (ALB) were also observed in subjects with MetS. The factors associated with MetS in the multivariate analysis were higher GGTP activity (OR per 5 unit increase – 1.23 (1.11–1.37); p<0.0001), a higher BMI (OR – 1.28 (1.1–1.52); p=0.003), a higher concentration of calcium (OR per 0.1 mmol/l increase – 1.79 (1.21–2.7); p=0.004), higher ALB levels (OR per 5 g/l increase – 1.76 (1.11–2.95), p=0.02); higher phosphorous levels (OR per 0.1 mmol/l increase – 0.82 (0.67–0.99); p=0.04), and a good household situation (odds ratio (OR) – 0.58 95% confidence interval (CI) (0.31–1.07); p=0.08).ConclusionCalcium and phosphorus levels are significantly associated with MetS in normal-weight individuals.