In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects.PREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy  and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI .http://www.clinicaltrials.gov No. NCT02698618).PREDICT will be the first multicentre clinical trial to test the adenosine-mediated vasodilatory effect of Ticagrelor on the microcirculation during PCI in diabetic patients. The results will provide important insights into the prospective beneficial effect of this drug in preventing microvascular impairment related to PCI (The online version of this article (doi:10.1186/s12933-017-0543-5) contains supplementary material, which is available to authorized users. Type 2 diabetes mellitus (T2DM) is associated with a significant increase in the risk of coronary artery disease. As the prevalence of diabetes is estimated to double in the next 10 years, the burden of cardiovascular disease associated with this condition will dramatically increase. Although, over the last two decades, cardiovascular mortality has declined considerably in the general population, a similar trend has not been observed amongst diabetic patients , both ac12 inhibitors, as it reduces the physiological clearance of adenosine by inhibiting its cellular uptake, thus increasing the plasma concentration of adenosine. As the primary aim of adenosine is achieving tonic and cellular protection during stress conditions  are more prevalent in patients with T2DM . Thus, tBy blocking the ENT1 nucleoside cell membrane transporter, Ticagrelor inhibits cellular uptake of adenosine and thus its physiological clearance, increasing the circulating levels of adenosine. Adenosine may protect the myocardium from both ischemic and reperfusion injuries via its potent vasodilator effect and/or through its anti-inflammatory and antiplatelet properties . PhysiolPrevious research from our group  has suggTherefore, Ticagrelor may be superior to Clopidogrel in providing microcirculatory protection during PCI procedures in patients with T2DM or pre-T2DM (primary hypothesis). Onset of treatment prior to PCI with Ticagrelor may be followed by a beneficial reduction in coronary microcirculatory parameters, as compared to Clopidogrel (secondary hypothesis).http://www.clinicaltrials.gov No. NCT02698618) is a prospective, multicenter, randomized, open-label study designed to investigate the protective effect of Ticagrelor over Clopidogrel on the coronary microcirculation during PCI in patients with T2DM or pre-T2DM. The primary endpoint aims to document (i) a decrease in coronary microcirculatory resistance caused by treatment onset  and (ii) a lower increase in microcirculatory resistance caused by PCI . A detailed list of endpoints is reported in Table http://www.cardiogroup.org website.The PRotective Effect on the coronary microcirculation of patients with DIabetes by Clopidogrel or Ticagrelor (PREDICT) trial  and the status of the microcirculation including measurement of coronary flow reserve (CFR) and Index of Microvascular Resistance (IMR) , 11 will2) [Randomization: Patients will be randomly assigned (1:1 ratio) to receive either Clopidogrel (600 mg loading dose followed by a daily dose of 75 mg) or Ticagrelor (180 mg loading dose followed by a dose of 90 mg b.i.d). The groups will be balanced according to the presence or absence of obesity  (Body Ma2)  with the3.1.Pre-PCI: Multimodal physiological evaluation  will be repeated.3.2.PCI: For all patients undergoing PCI, unfractioned heparin will be administered at the time of PCI. The PCI procedures will be performed using standard techniques using and second generation Drug Eluting Stents. Balloon pre-dilatation will be mandatory before stent implantation using a semi-compliant balloon with a diameter smaller than 75% of the distal reference vessel size in order to avoid confounding effects related to pre-dilation . Post-di3.3.Post-PCI: After stent implantation, multimodal intracoronary physiological evaluation will be repeated .PCI procedure: PCI procedure will be deferred for at least 48 h after the first administration of the study drug treatment in order to allow approximately 5 mean-half life times of their active metabolites, similar to a previously published study .3.1.Pre-In-hospital stay: High-sensitivity cardiac troponin and creatine kinase myoband (CK-MB) will be determined in blood samples taken after the intervention .In-hospital follow-up and data acquisition: Major adverse cardiac events as well as any bleeding complications occurring during in-hospital stay will be recorded  before the procedure will receive a 300 mg oral dose of ASA at the time of inclusion in the study. All patients will continue their chronic treatment after the study termination as prescribed by their cardiologist. Dual antiplatelet therapy regime (DAPT) after discharge will be decided by the responsible physician according to current recommendations, bearing in mind the recommendations on DAPT switching if required , 15.An intracoronary pressure and temperature sensor-tipped guidewire  will be used to measure distal coronary pressure and the index of coronary flow derived from the coronary thermodilution method as previously described . Three trrection  , according to the normality of their distribution, which will be tested with the Shapiro–Wilk test. Bartlett’s test will be performed to demonstrate homogeneity of variances between more than two groups. Primary endpoints will be assessed using the Student t test, if the samples are normally distributed or their variances are homogeneous; or Mann–Whitney U test, otherwise. P values will be corrected in order to account for the multiple endpoint. For the analysis of secondary variables, comparisons between continuous variables will be performed using the (paired or unpaired) Student t test or Mann–Whitney U test. The IMR at baseline, before PCI, and after PCI will be compared with an ANOVA for repeated measures or with the Friedman test, as appropriate. Comparisons between categorical variables will be evaluated using the Fisher exact test or the Pearson Chi square test, as appropriate. Correlations between continuous variables will be assessed using the Pearson or the Spearman rank correlation test. A 2-way ANOVA for repeated measures will be used to detect changes in IMR levels over time in the two study groups. Finally linear and logistic regression models will be carried out in order to identify predictors of periprocedural myonecrosis and delta-IMR. Analysis will be performed both in the full analysis set and a per protocol analysis and any differences between them would be the subject of explicit discussion and interpretation. In case of having multiple stenoses in some patient, additional adjusted analysis will be provided. Statistical analyses will be performed using the R statistical software [Categorical variables will be reported as frequencies and percentages. Continuous variables will be expressed as mean ± SD or as median . Other three centers in Spain will participate in patient enrollment: Hospital de Galdakao (Bilbao), Hospital Universitario de Cabueñes (Gijón), Hospital Puerta de Hierro, Majadahonda.The main purpose of the PREDICT trial is to test if Ticagrelor provides greater protection to the coronary microcirculation during PCI in diabetic patients compared to Clopidogrel as assessed by microvascular resistance indices. The results will provide important insights into the prospective beneficial effect of this drug in preventing microvascular impairment related to PCI. In the following paragraphs, we briefly discuss the rationale behind our study hypothesis.Instrumentation of atheromatous vessels during PCI, such as balloon dilation or stent implantation, may damage the subtended microcirculation and myocardium. The most dramatic presentation of this phenomenon is the so-called no-reflow phenomenon , in whicSeveral authors have proposed pharmacological strategies targeting the microcirculation to prevent peri-procedural damage. As cardiac biomarker release is a vague indicator of microcirculatory damage , the use of physiological techniques to measure modifications in microcirculatory resistance (such as the IMR) has been advocated  as a surIn patient with stable CAD, addition of Clopidogrel therapy results in an increase in endothelial function at the primary endpoint (assessed via reactive hyperaemic index) of 3 months. The improvement in endothelial function was already evident after 1 week of Clopidogrel therapy and seems to be not related to Clopidogrel effects on platelet aggregation .On the other hand, among patients, those with T2DM exhibited increased platelet reactivity compared to patients without diabetes despite combined treatment with Clopidogrel and aspirin even when a loading dose of Clopidogrel rather than small daily doses was used . The mec12 agents, the influence of Prasugrel or Ticagrelor on platelet reactivity in T2DM patients was object of studies demonstrating that Ticagrelor treated patients have overall lower platelet reactivity than patients on Prasugrel, independently of T2DM status or insulin treatment [Thus, after the introduction of new P2Yreatment . The effreatment  in the PAn ongoing randomised, prospective, controlled study  are also12 receptors and the improvement in microvascular endothelial function that we reported above, Ticagrelor may also protect microcirculation increasing the circulating levels of adenosine, Several studies have consistently shown that Ticagrelor inhibits the cellular uptake of adenosine. Intracellular adenosine is rapidly uptaken and metabolized to inosine by adenosine deaminase or transformed into adenine nucleotides by adenosine kinase [Beyond the antagonizing effect on P2Ye kinase  and there kinase  leading e kinase .Wittfeldt et al.  first deAdenosine is routinely used in the catheterization laboratory for the treatment of the no-reflow phenomenon during PCI, which constitutes an extreme manifestation of peri-procedural damage. No-reflow develops dramatically in response to vessel instrumentation, with contrast medium stagnation in epicardial arteries, persistent myocardial blush and, frequently, accompanying ECG and hemodynamic changes. This complication is the result of plugging of the coronary microcirculation by downstream embolization of micro-thrombi or atheroma dislodged from the culprit lesion as a result of its manipulation during PCI . ReperfuThe effects of adenosine on no-reflow have been investigated in numerous studies. A recent meta-analysis of seven randomized clinical trials supports the benefit of intracoronary adenosine in terms of post-PCI ST-segment resolution and reduced residual ST-segment elevation . AdditioThe response after adenosine administration is heterogeneous and associated with relevant differences in clinical and intracoronary physiological characteristics. Based on a study performed with intracoronary multimodal physiology, we recently reported that patients with T2DM or the metabolic syndrome  demonstrThis finding supports the hypothesis that the myocardial protective effect of Ticagrelor may be higher in patients with T2DM or the metabolic syndrome. This is of particular importance, as PCI in patients with diabetes has been associated with higher peri-procedural events than in non-diabetic patients.The role of adenosine in protecting the microcirculation remains controversial . This pr


Most hypertensive patients, despite a proper control of their cardiovascular risk factors, have cardiovascular complications, evidencing the importance of controlling and/or reversing target-organ damage. In this sense, endothelial dysfunction has been associated with the presence of cardiovascular risk factors and related cardiovascular outcomes. Since hypertension often clusters with other risk factors such as dyslipemia, diabetes and obesity, in this study we have investigated the effect of intensive multifactorial treatment on circulating vascular progenitor cell levels on high-risk hypertensive patients.We included108 hypertensive patients receiving intensive multifactorial pharmacologic treatment and dietary recommendations targeting blood pressure, dyslipemia, hyperglycemia and weight for 12 months. After the treatment period, blood samples were collected and circulating levels of endothelial  and smooth muscle (CD14+/endoglin+) progenitor cells were identified by flow cytometry. Additionally, plasma concentration of vascular endothelial growth factor (VEGF) was determined by ELISA.Most hypertensive patients  showed cardiovascular parameters within normal ranges at baseline. Moreover, body mass index and the majority of the biochemical parameters  significantly decreased overtime. After 12 months of intensive treatment, CD34+/KDR+ and CD14+/endoglin+ levels did not change, but CD34+/VE-cadherin+ cells increased significantly at month 12 [0.9(0.05–0.14)% vs 0.05(0.02–0.09)% P<0.05]. However, VEGF plasma concentration decreased significantly overtime .Long-term intensive treatment in hypertensive patients further improves cardiovascular risk and increases circulating EPCs, suggesting that these cells could be a therapeutic target. In the past, the goal of treating hypertension was merely blood pressure (BP) reduction, and antihypertensive therapy demonstrated to diminish cardiovascular events around 25% . UpdatedThe balance between endothelial injury and endothelial recovery is critical to the reduction of cardiovascular events . The injCirculating EPCs are bone marrow derived cells characterized by the expression of both hematopoietic CD34, CD133) and endothelial  surface markers  that hav3 and endIn the last years, the participation in vascular diseases of another circulating bone marrow-derived progenitor cell population has been reported . In thisPreviously, we have reported that the number of EPCs in treated hypertensive patients was not normalized despite showing cardiovascular parameters within normal ranges . Thus, tConsecutive consenting adult hypertensive patients with moderate, high or very high cardiovascular risk according to 2007 European Society of Hypertension/European Society of Cardiology (ESH/ESC) Guidelines for the management of arterial hypertension  who atteOnce the patient was included in the study, the treatment of all cardiovascular risk factors were reviewed and optimized aiming to achieve the highest therapeutic targets suggested by the guidelines for the management of arterial hypertension: systolic/diastolic BP (SBP/DBP) ≤140/90 mmHg, total cholesterol <175 mg/dL, LDL-cholesterol <100 mg/dL (80 mg/dL if possible), triglycerides <150 mg/dL, HbA1c ≤ 7%, and smoking cessation. For this purpose, all patients were prescribed an angiotensin converting enzyme (ACE) inhibitor or, if such a drug was contraindicated, an angiotensin II receptor antagonist (ARAII) irrespective of the BP level. If a patient had SBP/DBP >140/90 mmHg, diuretics, calcium channel blockers, and beta-blockers were added as needed. The combination of an ACE inhibitor and an ARAII could also be used. Patients were also prescribed a statin irrespective of fasting serum cholesterol concentration. Fibrates were added to statin treatment if the triglyceride concentration was also elevated (>350 mg/dL).If patients showed HbA1c >7%, an oral antidiabetic agent was started, and if high HbA1c value persisted they were added or switched to insulin. When indicated, platelet antiaggregants or oral anticoagulants were also prescribed. All smoking patients were invited to participate in smoking-cessation programs. Simultaneously, patients were recommended non-drug therapy, including weight reduction, moderation in the consumption of alcohol, physical exercise, reduced salt intake and follow a Mediterranean diet type or a Dietary Approaches to Stop Hypertension diet (DASH diet). During the study, patients were asked about their adherence to the recommendations in each visit. Patients were followed up by means of clinic visits one month after their inclusion in the study and every third month. After 12 months of follow up, we proceeded to the final visit in which all determinations of baseline  were repeated.The protocol of this study complies with the principles of the Helsinki Declaration and has been approved by the Ethics and Clinical Investigation Committee of Hospital Clínico San Carlos. Informed consent was obtained from all subjects.Medical records were carefully reviewed at an interview, and a thorough physical examination was performed. Gender, age, anthropometric measurements , SBP/DBP, smoking habit and personal history was recorded. Body mass index (BMI) was calculated.A sample of fasting venous blood was drawn for routine biochemical measurements and Service of Clinical Biochemistry at the Hospital Clínico San Carlos performed all analysis unless noted otherwise.Blood samples were processed within four hours after collection. Peripheral blood cells were analyzed by direct flow cytometry as previously described . BrieflyVEGF levels were determined using a commercially available kit . The concentrations were determined by comparison with a standard curve, following the manufacturer’s instruction.Qualitative variables were summarized by their frequency distribution as well as quantitative variables by their mean and standard deviation (± SD). The continuous non-normally distributed variables were summarized by the median and interquartile range (IQR: P25-P75). The Kolmogorov-Smirnov test was used to prove Gaussian distribution. In case of qualitative variables, comparison was evaluated by the test of χ2. For continuous normally distribute variables the T-Student test was used to compare two groups. The Mann-Whitney U test was used for continuous not normally distributed variables. The association between continuous variables was tested using the non-parametric Spearman’s correlations coefficient. As circulating vascular progenitor cells were not normally distributed, these data were log-transformed to improve their distribution for statistical testing, with back-transformed results for presentation in figures and tables. A multivariate linear regression analysis was fitted in order to evaluate the variables associated with circulating vascular progenitor cells. Adjustment was with those variables which, in the univariate analyses, showed a level of statistical significance of P<0.05, and/or were considered clinically relevant. Null hypothesis was rejected by a type I error minor than 0.05 (P<0.05). Statistical analyses were performed using the SPSS 17.0 statistical package.The clinical, biochemical characteristics of the participants and their treatments at start and after treatment intensification during 12 months are presented in Regarding the cardiovascular risk stratification, CD34+/KDR+ and CD34+/VE-cadherin+ cell levels did not differ significantly when cardiovascular risk increases according to the model of qualitative cardiovascular risk stratification taken from 2007 ESH/ESC Guidelines . Howeverth percentile) of CD34+/KDR+ and CD34+/VE-cadherin+ and lower of CD14+/endoglin+ cells  were younger, with less years since diagnosis of hypertension, and with lower BP. These associations were maintained in a multivariate analysis. No differences were found regarding other cardiovascular risk factors. Interesting, patients with previous cardiovascular disease  tended to have higher number of CD14+/endoglin+ cells than those without a cardiovascular event.The multifactorial intensive treatment for 12 months did not modify CD34+/KDR+ and CD14+/endoglin+ cells with respect to baseline . By contSince VEGF is one of the best characterized growth factors responsible of the mobilization of EPCs from the bone marrow , we inveOur data demonstrate that a long intensive multifactorial treatment aiming to achieve the highest therapeutic targets for traditional cardiovascular risk factors increases levels of circulating EPCs of hypertensive patients.EPCs reduction or dysfunction has been inversely associated with traditional cardiovascular risk factors and with the development of future cardiovascular events, having been revealed as a new cardiovascular biomarker , 13. TheSeveral studies have investigated the effect of drugs commonly used in the treatment of cardiovascular diseases on the number of EPCs and their functionality. Most studies have demonstrated that antihypertensive drugs such as ACE inhibitors, ARAII and calcium channel antagonists can improve the number and functionality of EPCs and that these effects are independent of the BP lowering effect –31. SimiIn this study, we have included hypertensive patients with added cardiovascular risk that have received an intensive and multifactorial treatment. Hypertensive subjects often have a cluster of risk factors that greatly augments the cardiovascular hazard of elevated BP . TherefoThe mechanisms by which the intensification of drug treatment of hypertensive patients may have a beneficial effect on circulating EPCs are not well-known. Cardiovascular risk factors cause oxidative stress that alters VEGF regulation by preventing the attachment to its receptor on bone marrow . Our patIn this paper we have also shown that hypertensive patients had an increase in the SMPCs CD14+/endoglin+ that did not change after the intensive treatment. Although several studies have shown the presence of SMPCs in atherosclerotic lesions , 40, theOur study has some limitations. We have not evaluated EPC functions in this study since our aim was to investigate the variation in the number of circulating vascular progenitor cells after 12 months of intensive therapy in order to justify its use as a biomarker of therapeutic efficacy, requiring to this purpose simple, rapid and reproducible methods as flow cytometry. During our study, only one patient suffered a cardiovascular event. These patients are currently being followed up in our Unit of Hypertension in order to evaluate whether changes in the number of EPCs showed in this study translate into a reduction of cardiovascular events. In addition, we know that in multifactorial interventions are not possible to clear out which part has been most efficient. Although, previous studies have indicated that most of the CVD benefit came from statin therapies.In conclusion, we have demonstrated that EPCs can be good therapeutic target in hypertensive patients, suggesting a new potential pharmacological mobilization therapy. In this sense, the use of cellular therapeutic strategies has emerged as a powerful tool contributing to cardiovascular regeneration. Thereby, different routes of EPCs administration such as autologous EPC injection, pharmacological mobilization and EPCs capture stents have demonstrated to stimulate the revascularization of ischemic vessels in different animal models of limb ischemia or myocardial infarction However the clinical transfer of EPC-based therapies has shown conflicting results, with only some trials reporting an improvement of cardiac function and a reduction of important clinical end-points , 46. Man


Focal segmental glomerulosclerosis (FSGS) often develops rapidly and frequently progresses to renal failure, while the recurrence rate after kidney transplantation is 20–50%. We performed low-density lipoprotein (LDL) apheresis before kidney transplantation in FSGS patients to prevent recurrence. Five adult patients with chronic renal failure due to FSGS undergoing living related donor kidney transplantation were investigated retrospectively. LDL apheresis was done 1-2 times before transplantation. Postoperative renal function and recurrence of FSGS were assessed. The patients were two men and three women aged 24 to 41 years. The observation period ranged from 60 days to 22 months. Preoperative LDL apheresis was performed once in one patient and twice in four patients. Blood LDL cholesterol levels were normal before LDL apheresis and remained normal both after LDL apheresis and after kidney transplantation. Additional LDL apheresis was performed once in one patient with mild proteinuria after transplantation. The renal graft survived in all patients and there was no evidence of recurrent FSGS. Although the observation period was short, FSGS did not recur in all 5 patients receiving preoperative LDL apheresis. These results suggest that LDL apheresis can be effective in preventing recurrence of FSGS after kidney transplantation. Like minimal change nephrotic syndrome (MCNS), focal segmental glomerulosclerosis (FSGS) often develops rapidly with severe proteinuria and edema. However, FSGS is often refractory or intractable with a high risk of progression to renal failure, unlike MCNS, and it has been reported that the recurrence rate of FSGS after kidney transplantation is 20–50% –6. To trThis study is a retrospective, observational, single-center cohort study. The study protocol was approved by the Institutional Review Boards at Tokyo Women's Medical University Hospital, Tokyo. Consecutive five adult patients with FSGS who underwent living related donor kidney transplantation were retrospectively registered as subjects in this study from July 1, 2015, to March 31, 2017. Each patient was informed about the outline of written informed consent before registration in the study. This study was conducted in accordance with Declaration of Helsinki. Clinical characteristics of the patients are described in 2 to 90.8 mL/min/1.73 m2 at one month after transplantation, while the latest eGFR values ranged from 31.7 mL/min/1.73 m2 to 83.4 mL/min/1.73 m2. Qualitative tests for urinary protein ranged from − to 2+ throughout the follow-up period. In three patients, the quantitative urinary protein-to-creatinine ratio ranged from 0.17 g/gCr to 0.87 g/gCr at one month after transplantation, while the latest values ranged from 0.04 g/gCr to 0.88 g/gCr. The graft survived with no rejection reactions in any of the patients. In addition, there were no signs or symptoms suggesting recurrence of FSGS in any of the patients. Biopsy of the transplanted kidney was not performed in any patient.Perioperative clinical parameters are described in We suggested that performing LDL apheresis before kidney transplantation in patients with FSGS can prevent the recurrence and good results were obtained.Persistent severe albuminuria reduces the serum albumin level and leads to a compensatory increase of albumin synthesis in the liver, but lipoprotein synthesis is also increased simultaneously and hyperlipidemia occurs. In addition, the enzyme catabolizing lipoproteins is excreted in the urine; this exacerbates hyperlipidemia. The resulting increased uptake of oxidized LDL by glomerular mesangial cells causes mesangial hyperplasia and leads to glomerular sclerosis . Furtherα and interleukin-8, are often increased in nephrotic syndrome including FSGS [LDL apheresis is performed to reduce lipid levels. It has been reported that improvement of hyperlipidemia protects the renal blood vessels, decreases oxidative stress, and suppresses induction of macrophages , 15. It ing FSGS , and eliing FSGS , suggestLDL apheresis was first introduced for treatment of familial hyperlipidemia . In 1988In patients with FSGS, recurrence of this disease after kidney transplantation can adversely influence the function of the transplanted kidney, so effective treatment of recurrence is important , 26. TheCouser  reportedIguchi et al.  reportedKorbet  examinedThis study's limitation is that the sample size consists only of five patients; further research with a larger sample is needed.We performed LDL apheresis in five patients before kidney transplantation to prevent recurrence of FSGS. Although the observation period was short, no recurrence was observed. It has already been reported that LDL apheresis is effective in treatment of FSGS and for recurrent FSGS after kidney transplantation. Our investigation suggested that performing LDL apheresis before transplantation may have a prophylactic effect against recurrence of FSGS. However, long-term evaluation of the outcome in a larger study is required to confirm these findings.


A lot of attention has been paid to the relationship of blood pressure and dementia because epidemiological research has reported conflicting evidence. Observational data has shown that midlife hypertension is a risk factor for cognitive decline and dementia later in life, whereas there is evidence that low blood pressure is predictive in later life. The aim of the present study was to examine the association between dementia and blood pressure measured up to 27 years (mean 17.6 years) prior to ascertainment.In Nord-Trøndelag County, Norway, incident dementia data were collected during 1995–2011, and the diagnoses were validated by a panel of experts in the field. By using the subjects’ personal identification numbers, the dementia data were linked to data from the Nord-Trøndelag Health Study (the HUNT Study), a large, population-based health study performed in 1984–1986 (HUNT 1) and 1995–1997 (HUNT 2). A total of 24,638 participants of the HUNT Study were included in the present study, 579 of whom were diagnosed with Alzheimer disease, mixed Alzheimer/vascular dementia, or vascular dementia. Multiple logistic regression analyses were conducted to analyze the association between dementia and blood pressure data from HUNT 1 and HUNT 2.Over the age of 60 years, consistent inverse associations were observed between systolic blood pressure and all-cause dementia, mixed Alzheimer/vascular dementia, and Alzheimer disease, but not with vascular dementia, when adjusting for age, sex, education, and other relevant covariates. This was observed for systolic blood pressure in both HUNT 1 and HUNT 2, regardless of antihypertensive medication use. There was an adverse association between systolic blood pressure, pulse pressure, and Alzheimer disease in individuals treated with antihypertensive medication under the age of 60 years.Our data are in line with those in previous studies demonstrating an inverse association between dementia and systolic blood pressure in individuals over the age of 60 years. We cannot exclude a survival effect, however. Among middle-aged subjects (<60 years), elevated systolic blood pressure and pulse pressure were associated with eventual Alzheimer disease in individuals who reported using antihypertensive medication.The online version of this article (doi:10.1186/s13195-017-0262-x) contains supplementary material, which is available to authorized users. Blood pressure (BP) level is a commonly investigated vascular risk factor. Results reported to date in the epidemiological literature on BP and dementia are conflicting and unclear because researchers have faced challenges when examining individuals with declining cognition over time that impact findings . Cross-s2, which is comparable to the size of Wales. During the study period of 1995–2011, the largest of six small towns had a population of 21,000. According to census data of 2014, the population of Nord-Trøndelag County was 135,000 and stable, with a net outmigration of 0.3% per year. The population is predominantly of Caucasian ethnicity. There are 32 nursing homes in the county, as well as two regional hospitals, located in Namsos and Levanger.Nord-Trøndelag County is located in central Norway and is a mostly rural and sparsely populated area. The geographic region covers 22,414 kmThe Helse Undersøkelse Nord-Trøndelag  was initiated in 1984–1986 as a health survey that addressed four main topics: hypertension, diabetes, quality of life, and tuberculosis as well as other lung diseases. The subsequent survey, Helse Undersøkelse Nord-Trøndelag  expanded the scientific program substantially and collected a large number of health-related data, as described in detail previously –17. BrieDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition, which sets criteria standards according to clinical examination, patient and caregiver history, blood samples, and imaging of the brain [The Health and Memory Study of Nord-Trøndelag (the HMS Study) had an aim to establish a database suitable as a basis for a large number of studies of dementia, and extensive information on the ascertainment process, measurements, and findings have been published previously . Brieflyhe brain , 20. IniPanel 1 consists of a total of 1259 patients referred to the hospital for suspicion of cognitive decline, and 15 patients were excluded because of dual registration, 219 lacked journal documentation, 27 had no dementia present, and 78 were diagnosed with mild cognitive impairment. Thus, a total of 920 patients were included in panel 1. Of 979 patients initially identified in panel 2, 197 refused to participate, 24 patients were excluded because of severe illness, 17 died, 1 moved, and 20 were excluded for unknown reasons. Additionally, 100 patients were excluded because they had no dementia, and 107 were excluded for dual assessment. Ultimately, 513 patients were included in panel 2, comprising of a total of 1433 patients in the HMS Study Fig. .Fig. 1Fln = 27,238), and 24,059 participants had complete covariate data  were measured two times, and the second reading was used for our analyses. Heart rate, height, and weight were measured in HUNT 1 following a previously described protocol . SociodeBP measurement procedures carried out during HUNT 2 were identical to those in HUNT 1, with the exception that automated measures were based on oscillometry . SBP, DBP, and heart rate were read three times with 1-minute intervals. In our analyses, the mean value of the second and third readings was used. Mean arterial pressure (MAP) was calculated as one-third SBP + two-thirds of DBP. Pulse pressure (PP) is the difference between SBP and DBP readings.2 tests and independent-samples t tests were used for the comparison of categorical and continuous variables between all-cause dementia (n = 579) and no dementia . We used logistic regression to examine the association between dementia and BP with SBP, DBP, PP, and MAP as principal predictors entered as continuous variables per 10 mmHg as the measurement unit. A total of four sets of analyses were run separately for both HUNT 1 and HUNT 2 to examine the relationship between BP and all-cause dementia, AD, mixed AD/VaD, and VaD. Stepwise analyses were performed separately, entering SBP, DBP, MAP, and PP alone (model 1); adjusting for age, sex, and education (model 2); entering clinical variables in blockwise fashion (model 3); and finally adding self-reported data (model 4). Interaction effects between sex and age on SBP, DBP, MAP, and PP were examined separately by including interaction terms in fully adjusted models. In separate models, linearity assumptions for continuous BP were examined by introducing polynomial functions and examining predictions in scatterplots. SBP, DBP, MAP, and PP were entered separately as a quadratic measure in fully adjusted models. Age was categorized in 5-year intervals, and results are presented as age entered in models as a continuous variable. All statistical analyses described above were performed using IBM SPSS Statistics version 21  and Stata version 13  software.Pearson’s χThe study population consisted of 24,059 subjects without dementia  and 579 with dementia . Descriptive statistics are shown in Table Multiple logistic regression analyses were performed for the total sample and separately for the groups less than and greater than or equal to 60 years of age at the time of HUNT 1 (1984–1986). The results for SBP in the total sample are shown in the upper part of Table p < 0.01). To further examine this interaction effect, the effect of SBP was examined in different age strata. Splitting the sample into subjects younger than 60 years old at HUNT 1 and 60+ years old at HUNT 1 showed that all the apparent protective effects of high SBP occurred in the oldest group. There was a significant sex × BP interaction effect among subjects younger than 60 years old; however, no sex × BP interaction effect was observed among subjects ≥60 years. The results are shown in the lower part of Table We tested for an interaction effect between sex and SBP and between age and SBP. The age × SBP effect was significant  years prior to symptom presentation of dementia, AD, and VaD. One of the findings was that high BP did not seem to be a risk factor for dementia when adjusted for age, sex, education, and other covariates in the total sample. Upon further examination, we found that age interactions were apparent in the total sample that required further stratified analyses. Interestingly, in persons 60 years or older, SBP was inversely associated with all-cause dementia, mixed AD/VaD, and AD, but not with VaD. Conversely, among middle-aged subjects (<60 years old), elevated SBP and PP were associated with eventual AD in participants who reported using antihypertensive medication.The inverse association of SBP with all-cause dementia, mixed AD/VaD, and AD might seem paradoxical because hypertension is generally acknowledged as a risk factor for cognitive decline and dementia –4. HowevOur findings raise a question whether high SBP actually has a protective effect against developing AD in a targeted population over 60 years of age. There is evidence to support this because a recent Mendelian randomization study of AD using single-nucleotide polymorphism revealed that higher SBP was associated with lower AD risk . In addiIn line with previous published studies, our data indicate that higher BP in midlife was associated with greater dementia risk in those who were treated with antihypertensive medication. Midlife BP data have previously been examined in a number of studies providing substantial evidence that there is a longitudinal association between midlife BP and worse cognitive function in later life –34. PP wResearchers in a number of studies have examined whether BP variability over time plays a significant role in the onset and progression of dementia , 39, 40.It is well known that vascular factors contribute to dementia. The dementia spectrum has previously been described on one end with pure dementia of vascular type, on the other end among those with pure AD, and in between among the largest group with pathologies from both AD and vascular damage –45. On tOur study has a number of strengths, including the very large sample size and the longitudinal design with a long period of follow-up. The dementia diagnoses were validated by experts in the field among a unique, large, population-based sample, and we examined a large set of variables that permitted adjustments and stratification into subgroups. Missing data are hard to avoid when examining longitudinal data, and data analyses were performed using complete-case data. Imputation analyses were not performed, as the data were assumed to be missing at random. Selection bias was probably moderate because the HUNT-HMS study is a prospective, population-based study with a high response rate that provides information about BP measured prospectively up to 27 years prior to onset of dementia. The dementia diagnoses were set by experienced clinicians by using the standardized ICD criteria. However, ascertaining the subtypes of dementia diagnoses was retrospective and based on access to comprehensive medical records from both panels, which were therefore sufficient to subclassify according to the ICD criteria. Furthermore, cognition assessments were not initiated in the county hospitals until 1995, leaving a questionable period during startup in 1995–2000, when scarce numbers of dementia cases were ascertained. A larger fraction of dementia cases were diagnosed during the period 2000–2009, and most cases were identified in 2009–2011. Cognition was not evaluated during HUNT 1 or HUNT 2, but participants were required to complete several questionnaires and underwent extensive screening that intuitively required intact cognition among participants . AlthougWe conclude that elevated BP does not seem to be a risk factor for dementia when adjusted for age, sex, education, and other covariates. In fact, in persons over 60 years of age, SBP was inversely associated with a prospective dementia diagnosis, whereas in the middle-aged subjects (<60 years old), elevated SBP and PP were associated with eventual AD in participants who reported using BP-lowering medication. These findings are consistent with previously published studies and appear to be dependent on factors such as age, hypertension chronicity, and antihypertensive medication use. Future population-based prospective studies with repeated BP measurements examining BP variability, as well as more detailed data on BP-lowering agents, are needed because the nature of the association between BP and dementia remains unclear.Additional file 1:Description of baseline data and missing data. (DOCX 16 kb)Additional file 2:Supplementary Tables 1,2 and 3 present the results on the association of SBP, DBP, MAP, and PPand dementia using multiple logistic regression analyses for the total sample (Table 1); and in participants<60 (Table


Complications of hypertension are particularly common in people of African descent but previous reports had suggested rarity of hypertensive retinopathy in black Africans. We evaluated retinal changes among Nigerian hypertensive patients and determined their relationship with renal function.-1.154 × (Age)-0.203 ×  × (1.210 if black).Consecutive Hypertensive patients who were ≥18 years were selected for the study. Socio-demographic characteristics, anthropometric parameters and blood pressure were measured. All patients had ophthalmoscopic examination and retinal changes were graded according to Keith-Wegener’s classification. Blood samples were taken for blood urea nitrogen, lipids and C-reactive protein; and urine was collected for creatinine and microalbuminuria. Serum creatinine was determined using modified Jaffe method and estimated glomerular filtration (eGFR) was calculated using MDRD equation: 186 × (Creatinine/88.4)p = 0.001) and had longer duration of hypertension (p = 0.001). Similarly, hypertensive patients with retinopathy had higher total cholesterol and low density lipoprotein cholesterol . However, eGFR was lower in individuals with retinopathy (46.2 ml/min/1.73) than those with normal retinal (55.9 ml/min/1.73) findings, p = 0.019. Multi-variable adjusted odds ratios showed increased probability of retinopathy with age  and body mass index .Of the 240 patients studied, 187 (78 %) had one form of retinopathy or the other. While 85 (35.4 %) patients had grade 1 retinopathy, 87 (36.3 %) had grade 2, 13 (5.4 %) had grade 3 and 2 (0.83 %) had grade 4 respectively. Comparison of patients with and without retinopathy showed that, the former were older (pari passu with renal damage as consequences of long standing hypertension.Hypertensive retinopathy is a common clinical finding among hypertensive Nigerians and may occur  Systemic hypertension is a major public health concern that affects more than one billion people world-wide . The pre-1.154 × (Age)-0.203 ×  × (1.210 if black). Where unit of eGFR = mL/min/1.73 m2, serum creatinine = μmol/L and age = years. Serum Uric Acid was determined using Uricase-PAP method. All the kits used were manufactured by Agappe Diagnostics International and supplied by NUMS Diagnostics Nigeria Ltd. Suleja.The study was a descriptive cross sectional evaluation of retinal morphology and renal function among hypertensive patients that were managed at the Medical Out-Patient Department (MOPD) of our hospital. Consecutive hypertensive patients seen at the MOPD were recruited if they were ≥18 years and gave informed consent. Hypertensive patients, who were diabetic, had sickle cell anaemia, had history of glaucoma, pregnant and those with secondary hypertension were excluded from the study. Ethical approval was obtained from the Ethics and Research Committee of the University of Ilorin Teaching hospital, Nigeria. The socio-demographic characteristics of the participants were obtained and a thorough history including the duration of hypertension, drug therapy and compliance was taken. The anthropometric parameters, blood pressure and other relevant clinical examination were performed on the patients. Blood pressure was measured at the left arm in a comfortable sitting position after about 10 min rest using standard mercury sphygmomanometer (Accoson) with an appropriate cuff. However, if the blood pressure was equal or greater than 10 mmHg at the right arm, the latter blood pressure was used as the blood pressure of the subjects. An average of three measurements was taken as the patient’s blood pressure. Hypertension was defined according to the JNC VII (BP ≥ 140/90 mmHg or anti-hypertensive use) . The intP < 0.05.Statistical analysis was performed using the SPSS Version 15  and the numerical values were presented as mean ± SD. Student t-test was used to compare means of continuous variables while chi-square test was used to compare means of proportions. Means of variables of interest in patients with and without retinopathy; and those with ACR ≤300 mg/g and >300 mg/g were compared using independent t-test. Relationship between retinopathy and other variables of interest were determined by Spearman’s Rank correlation method. Those variables that have no significant correlations with retinopathy were excluded from analysis and the strength of association of each of the remaining variables was assessed using partial correlation statistics. Binary logistic regression was used to determine predictors of retinopathy and the products were expressed as odd ratio with 95 % confident interval. A statistically significant association was set at 2 which is in the over-weight category. The mean total cholesterol was 5.9 ± 1.5 mmol/l) while the mean of HDL-c was 0.9 ± 0.2 mmol/l with coronary artery disease risk ratio of 6.6. Median of the eGFR was 49.3 (range 16.5–167.2) mL/min/1.73 m2 which suggests that significant number of the patients had reduced kidney function. Similarly, the median of ACR was 93.9 (3.3–1931.3 mg/g) which also suggests that a good number of subjects had significant albuminuria.Two hundred and forty hypertensive patients comprising of 160 (66.7 %) women and 80 (33.3 %) men were studied with mean age of 58.9 ± 12.1 years. Baseline clinical and biochemical characteristics of the patients are shown in Table Figure p = 0.001) and had longer duration of systemic hypertension (p = 0.001) as shown in Table p = 0.017, p = 0.041 respectively). On the other hand, eGFR was lower in individuals with hypertensive retinopathy (46.2 ml/min/1.73) compared with those with normal retinal (55.9 ml/min/1.73) findings, p = 0.019. However, body mass index, blood pressure indices, C-reactive protein and ACR were similar between patients with and without retinopathy. Similarly, patients on drug combinations that included angiotensin converting enzyme inhibitors (ACEI) were compared with those on combinations without ACEI. All parameters compared were similar except ACR which was lower in those on ACEI than those not on ACEI. The median of ACR was 77.3 (5.78–1931.3 mg/g) in the former and 104.6 (3.34–1706.3 mg/g) in the latter. In addition, fewer patients on ACEI (40.4 %) have grades II-IV retinopathy compared with those not on ACEI (46.4 %), p = 0.346.When patients with hypertensive retinopathy were compared with those without retinopathy, the former were older (Comparison of patients with ACR ≤300 mg/g against those who had ACR >300 mg/g is presented in Table p = 0.001) and body mass index Correlates of hypertensive retinopathy are shown in Table Systemic hypertension remains the most prevalent cardiovascular risk factor in indigenous African population and a major cause of cardiovascular events. This prospective cross sectional study evaluated common complications of the eye and the kidneys among hypertensive individuals. The prevalence of hypertensive retinopathy among the study participants was 78 %. This prevalence is comparable with that of Ladipo , 12, 13,Patients who had retinopathy are older than those with normal retinal examination and positive correlation was observed between age and retinopathy. Age has been demonstrated as an independent predictor of retinopathy in patients with hypertension in other studies , 18. AgeBlood pressure indices (systolic and diastolic blood pressures) have been found to be associated with risk of development of hypertensive retinal changes , 20. Thip = 0.019. Similarly, a significant negative correlation was observed between the presence of retinopathy and eGFR . These results show that a significant number of our hypertensive patients had reduction in their renal function and this may occur simultaneous with other end organ consequence of the disease including retinal changes. In addition, ACR showed that a significant number of the patients studied had albuminuria which is an indication of glomerular dysfunction [Analysis of renal function among the study participants showed that eGFR was lower (46.2 ml/min/1.73) in those with retinopathy than those without (55.9 ml/min/1.73), function . When pafunction . Long stfunction .p = 0.001) and body mass index . Obesity is considered to be a major cardiovascular risk factor and microalbuminuria is an indication of renal disease. Indeed, retinopathy, LVH and microalbuminuria are considered as evidence of target organ damage in systemic hypertension. Our study further confirmed the beneficial role of ACEIs in the management of systemic hypertension [Multi-variable adjusted odds ratios showed increased probability of retinopathy with age (odds ratio-1.08, rtension . It is wThis study was limited by over representation of women in our study participants which is a reflection of health seeking behaviours among hypertensive patients seen in our practice. Therefore, it may be difficult to generalize our result to our population. Secondly, direct ophalmoscopy was employed in the assessment of the retina in our patients. Although, this is not inferior to retinal photographs but might have provided opportunity for further reviews.pari passu with renal damage as consequences of long standing hypertension. The presence of hypertensive retinopathy may be an indication for further assessment of affected individual especially the renal function.Hypertensive retinopathy is a common clinical finding among hypertensive Nigerians and occurs


Although moderate-intensity continuous training (MICT) has been the traditional model for aerobic exercise training for over four decades, a growing body of literature has demonstrated equal if not greater improvement in aerobic capacity and similar beneficial effects on body composition, glucose metabolism, blood pressure, and quality of life from high-intensity interval training (HIIT). An advantage of HIIT over MICT is the shorter time required to perform the same amount of energy expenditure. The current brief review summarizes the effects of HIIT on peak aerobic capacity and cardiovascular risk factors in healthy adults and those with various cardiovascular diseases, including coronary artery disease, chronic heart failure, and post heart transplantation. Such programs employing moderate-intensity continuous training (MICT) typically increase peak oxygen consumption (VO2) by 10–30%, with greater improvements associated with lower baseline fitness, higher intensity exercise, and longer program duration1. Additional benefits of MICT include modest blood pressure (BP) reduction, improved glucose and lipid metabolism, and mood elevation2.Aerobic exercise training has been extensively employed for several decades to improve functional capacity and cardiovascular (CV) risk factors in both healthy adults and those with cardiovascular disease (CVD). The traditional model for such training is typically a short (5–10 minute) warm up followed by 20–60 minutes of sustained moderate-intensity aerobic activity at 40–85% maximal aerobic capacity2 interspersed among periods of lower intensity is known as high-intensity interval training (HIIT). Although HIIT has received relatively little attention as a therapeutic modality until the past decade, numerous recent reports have documented increases in peak VO2 and improvement in several CV risk factors similar to or greater than those observed with MICT. This brief review will summarize these salutary effects of HIIT in healthy adults, those with CV risk factors, and those with established CVD.When performing aerobic exercise outside of a gym or cardiac rehabilitation (CR) program, individuals often vary the exercise intensity with short sprints as during a soccer or basketball game or in ascending hills on a bicycle. A program with such alternating short periods of high-intensity exercise at >85–90% peak VO3. The current review focuses on studies that have employed the AIT form of HIIT, given its greater applicability to the general population and individuals with CV risk factors and CVD. An advantage of both SIT and AIT over traditional MICT is their shorter time requirement to achieve a similar energy expenditure.HIIT can be divided into two distinct subtypes. Sprint interval training (SIT) typically consists of 4–6 cycles of 20–40-second “all out” sprints followed by 4–5 minutes of recovery. Because of SIT’s extreme intensity, most SIT studies have been limited to healthy young individuals. In older populations and those with CVD, HIIT has been employed in the form of aerobic interval training (AIT), which is performed at lower intensities than SIT but for longer periods. A typical AIT protocol consists of 4–6 cycles, each comprising 4 minutes of exercise at 80–95% peak capacity followed by 3–4 minutes of recovery, performed on a treadmill or cycle ergometer2 similar or superior to those elicited by MICT4. In addition, studies in mice and rats have demonstrated reductions in body mass, BP, and oxidative stress; augmented endothelial function; and improved metabolism in fat, liver, and skeletal muscle6. Of note, Wistar rats that underwent 5 consecutive days of HIIT on a treadmill up to 7 days before experimental ischemic reperfusion injury sustained 35–50% smaller myocardial infarctions (MIs) than did sedentary rats7. A similar reduction in infarct size has been demonstrated after MICT protocols8.Aerobic exercise programs using HIIT in animal models have shown large improvements in peak VO2 of 4.9 mL/kg/minute following HIIT, which was greater than that seen with traditional MICT9. Larger increases were observed among individuals with lower baseline fitness and in interventions longer than 10 weeks. Improved skeletal muscle mitochondrial function and pulmonary oxygen uptake kinetics have been demonstrated after only six HIIT sessions over 2 weeks in healthy untrained men10. Although occasional studies have failed to show superior effects of HIIT over MICT on peak VO2, these studies generally employed a program duration shorter than 10 weeks3. Because equivalent energy expenditure can be accomplished in less time with HIIT than with MICT, this may allow shorter exercise sessions with HIIT, thereby improving adherence.In healthy adults, a meta-analysis that included 723 healthy adults aged 18–45 years old from 28 controlled trials of 3–24 weeks’ duration showed a large absolute increase in peak VO13. The equivalent anthropometric changes might be attributed to the similar total energy expenditure with the two programs in those studies.Given the frequent association of obesity with low fitness and with CV risk factors such as hypertension, glucose intolerance, and dyslipidemia, a strong rationale exists for aerobic exercise training in such individuals. In three studies 3–6 months in duration, similar improvements in body mass index and waist circumference were observed in overweight/obese participants following both MICT and HIIT14. In such individuals who were not receiving antihypertensive drugs, HIIT for ≥12 weeks appears to provide a similar antihypertensive effect3. For example, 16 weeks of MICT or HIIT led to similar reductions of systolic (10 mmHg) and diastolic (6 mmHg) BP in middle-aged adults with elevated BP at baseline13. A 12-week HIIT program in overweight/obese adolescents with borderline hypertension also elicited significant reductions in both systolic BP (9 mmHg) and diastolic BP (6 mmHg)15.Traditional MICT exerts significant reduction of BP in hypertensive adults, especially those with suboptimal baseline BP control16. Similar effects on blood lipids are observed with HIIT17. Modest increases of HDL-C with HIIT required 8 or more weeks of training and occurred in only 3 of 10 such studies17. Given these inconsistent effects on HDL-C without benefit on other lipid fractions, neither HIIT nor MICT can generally be recommended as primary therapy for the treatment of dyslipidemia.Among individuals with dyslipidemia, traditional MICT typically elicits modest increases in high-density lipoprotein cholesterol (HDL-C) but exerts no consistent effect on low-density lipoprotein cholesterol or triglycerides18 and has been shown in both healthy adults19 and those with metabolic syndrome13. Improved oral glucose tolerance test results have been consistently reported after HIIT20. Fasting blood glucose did not change in studies of less than 12 weeks’ duration but declined in four of seven longer studies3. Small studies have found improved glycemic control in patients with type 2 diabetes23.Substantial evidence suggests that HIIT improves glucose metabolism to a similar or greater extent than does MICT. Augmented insulin sensitivity occurs as early as 2 weeks after the initiation of HIITIncontrovertible evidence for the benefits of MICT in patients with CVD has accumulated over the past four decades through hospital-based CR programs involving patients after acute MI, coronary revascularization, valvular surgery, and those with chronic heart failure (CHF). Similar, though less extensively studied, salutary effects of HIIT have been demonstrated in patients with CVD and are reviewed below.Coronary artery disease. Multiple studies have documented the benefit of HIIT in patients with coronary artery disease (CAD), the most prevalent form of heart disease in developed countries. A meta-analysis of 229 patients with CAD demonstrated a 1.5 mL/kg/minute larger mean increase in peak VO2 with HIIT than with MICT24. A larger meta-analysis that included 472 CAD patients showed a similarly augmented gain in peak VO2 (1.8 mL/kg/minute mean difference) compared with MICT25. In this latter analysis, no differences in blood glucose or lipids were observed between the groups. However, resting heart rate (-1.8 beats/minute) and body weight (-0.5 kg) declined slightly after MICT but not HIIT. A recently published randomized trial also showed a significantly larger increase in peak VO2 after 8 weeks of HIIT compared to MICT (4.5 versus 2.5 mL/kg/minute), respectively26.Chronic heart failure. Although CR was not approved until 2014 by the Center for Medicare and Medicaid Services for patients with CHF, considerable evidence has accrued on the benefits of HIIT in this population. One of the first studies to examine the effect of HIIT in CHF patients showed a remarkable 46% increase in peak VO2 in nine older patients (mean 75 years) with post-MI CHF versus an increase of only 14% with MICT27. Favorable left ventricular remodeling and increased left ventricular ejection fraction occurred only after HIIT. Three recent meta-analyses have confirmed a larger increase in peak VO2 with HIIT than MICT in CHF patients30. Haykowskyet al.28 showed a mean 2.1 mL/kg/minute larger increase in peak VO2 with HIIT in seven studies encompassing 168 patients. In a meta-analysis by Smartet al.29 involving 212 patients who performed HIIT and 66 who performed MICT, the mean improvement in peak VO2 was 1.0 mL/kg/minute larger after HIIT. A very large meta-analysis that included 74 exercise-based CR trials involving 5877 participants showed a 23% mean increase in peak VO2 among patients receiving HIT versus a 13% increase in those undergoing MICT30. Of note, withdrawal from the CR program was lower with HIIT. It should be noted that all of the studies and meta-analyses cited above excluded patients with CHF and preserved ejection fraction (HFpEF), who comprise 30–40% of the CHF population. Studies of HIIT are clearly needed in this latter group.Heart transplant recipients. Although data remain limited regarding the effects of HIIT in heart transplant recipients, available evidence suggests a similar benefit as seen with MICT. Compared to a usual care control group, 24 stable heart transplant recipients 1–8 years post transplantation demonstrated a 3.6 mL/kg/minute higher peak VO2 after 1 year of HIIT31. In a study of 16 patients ≥12 months post transplantation, 8 weeks of HIIT induced a larger increase in peak VO2 than did MICT (4.9 versus 2.6 mL/kg/minute)32.26 and CHF33, cardiac transplant recipients32, and generally healthy older adults34. Such improvement in QOL may reinforce the patient’s motivation to continue exercise participation.Although quality of life (QOL) is often considered a “softer” outcome variable than changes in physiological indices, it is probably a more relevant variable to patients. In this context, both MICT and HIIT have elicited improvement in QOL in a variety of clinical settings. For example, improvement in QOL after HIIT has been reported in patients with CAD30. A similar finding was reported in an analysis of 4846 CAD patients from three Norwegian CR centers35. In this study, major complications were one per 129,456 hours of MICT and one per 23,182 hours of HIIT. Nevertheless, HIIT may not be appropriate for frail older adults, those with significant orthopedic, neurological, or balance difficulties, those with marked obesity, or those with severe deconditioning. In such individuals, an initial low-to-moderate-intensity exercise program appears to be preferable.An important concern in prescribing any exercise program, especially in older adults and patients with CVD or other comorbidities, is safety. To date, the evidence suggests that HIIT is well tolerated to a similar extent as MICT. In the large meta-analysis of CHF patients previously mentioned, no deaths were attributed to exercise training regardless of intensity27 and muscle mitochondrial capacity18. In addition, sarcoplasmic reticulum calcium uptake was augmented by HIIT but not MICT, likely owing to an increased ability to perform high-intensity muscle contractions25. Another salutary effect of HIIT is to enhance flow-mediated dilation of the brachial artery, a measure of vascular endothelial function mediated in part by increased nitric oxide availability27. Finally, increased cardiac stroke volume has been reported after HIIT in obese women36, sedentary middle-aged adults37, and patients with CHF27.Given the substantial benefits of HIIT in a wide variety of settings, insights into the biochemical and molecular adaptations accompanying HIIT are worthy of inquiry. In patients with obesity, metabolic syndrome, or CHF, HIIT induced increases in peroxisome proliferator-activated receptor γ co-activator (PGC)-1α, a master regulator of oxidative phenotype2, without a significant difference in serious adverse events in appropriately selected individuals. Future studies should explore the long-term effects of HIIT on health outcomes as well as its effects when combined with dietary, drug, and cardiac device interventions in patients with CV disease.Although less thoroughly investigated than traditional aerobic training programs using MICT, HIIT appears to share similar salutary effects, with generally larger increases in peak VOThe views expressed are those of the author and do not necessarily represent those of the National Heart, Lung, and Blood Institute or the U.S. Department of Health and Human Services.


Diabetes-associated microvascular complications such as retinopathy and neuropathy often lead to end-organ and tissue damage. Impaired skin microcirculation often precedes the detection of other advanced diabetic complications. The ANS-1 system contains a redesigned sympathetic skin response (ANS-1 SSR) device that measures sudomotor function, a photoplethysmography sensor, and a blood pressure device to comprehensively assess cardiac autonomic neuropathy and endothelial dysfunction. The purpose of this study was to determine the relationships between the ANS-1 SSR amplitude measured at the: (a) negative electrode (Nitric Oxide [NO] Sweat Peak) with microvascular diseases and associated vascular blood markers and (b) positive electrode (iSweat Peak) with C fiber function.n = 50 and retinopathy patients n = 50) completed the ANS-1 system evaluation and a basic sociodemographic and medical history questionnaire, including a quality of life measure (SF-36). A small sample of blood was drawn to determine levels of homocysteine, blood urea nitrogen (BUN), C-reactive protein (CRP), and fibrinogen. Symptoms of peripheral foot neuropathy were assessed with a scale from 1 (none) to 10 (the worst). We used Spearman rank correlations, independent samples t-tests, and receiver operating characteristic curves to determine the specificity and sensitivity of the NO Sweat Peak as a potential screening marker of retinopathy.All participants  to detect retinopathy. The NO Sweat Peak response marker inversely correlated with BUN , homocysteine , fibrinogen , the Cardiac Autonomic Neuropathy score , and the heart rate variability Total Power , and it positively correlated with the Photoplethysmography Index . The ANS-1 system sudomotor response marker iSweat Peak inversely correlated with the severity of symptoms on the peripheral neuropathy scale .The ANS-1 System Cardiometabolic Risk Score and all indicators of quality of life on the SF-36, other than Emotional Role Functioning, were significantly worse in the retinopathy patients. The sudomotor response marker NO Sweat Peak had a sensitivity of 88% and a specificity of 68% (Area Under the Curve = 0.81, The results of the study show that this new method of measuring sympathetic skin response should be useful for detecting the earliest manifestations of microvascular disease and symptoms of C fiber dysfunction. Impaired skin microcirculation may be among the earliest manifestations of autonomic neuropathy and often precedes the detection of other diabetic complications . The diaBesides being a huge health problem, microvascular complications of diabetes are also costly. The CODE-2 study in the United Kingdom revealed that the presence of microvascular complications increased the total treatment costs of diabetes by 2.5-fold compared to patients without these problems . A similStandard guidelines for diabetes control and care increasingly recommend early detection of complications to maximize treatment options . HoweverThe ANS-1 system contains a sympathetic skin response (SSR) device to non-invasively screen for the small cholinergic fiber density and microcirculation state –11. PrevThe purpose of this study is to assess the accuracy of the ANS-1 system to detect microcirculatory disorders, inflammatory markers, and peripheral neuropathy symptoms in patients with retinopathy, since these conditions may often coexist.The study was conducted with the approval of the University of Miami Institutional Review Board for human subjects research.n = 142) were identified through referrals to the University of Miami Miller School of Medicine from November 2015 to January 2017. Out of 108 eligible participants, 50 healthy subjects and 50 patients with retinopathy were enrolled in the study, and their data were used for analysis. Six subjects in the healthy group were later confirmed to have neuropathy, one subject in the healthy group had blood drawn with the wrong tube, and one retinopathy patient’s ANS-1 assessment failed. Thus, we excluded the data from these 8 participants.Potential participants (Inclusion criteria were: (a) 18+ years of age for patients with retinopathy and 40+ years of age for healthy participants; (b) English or Spanish speaking; (c) ability to provide written informed consent; and (d) willingness to have blood drawn. Exclusion criteria were: (a) women who were pregnant; (b) for healthy subjects, kidney or thyroid disease, peripheral neuropathy, or taking any anti-inflammatory medication current use of alpha or beta blockers or corticosteroids; or (c) contraindications to the use of the ANS-1 system, including presence of an automatic implantable defibrillator, erratic, accelerated, or mechanically-controlled irregular heart rhythms, arterial fibrillation/flutter, or any implanted electronic device.The ANS-1 is an FDA cleared and patented system  that contains three modules: (a) a SSR device, (b) a plethysmography sensor, and (c) a blood pressure device. The SSR device was named SudoPath, and the plethysmography sensor and blood pressure device were named TM-Oxi before the FDA clearance of the ANS-1 system. In addition, the ANS-1 system replaced the ES Complex system  and integrated the ES Complex system algorithms for the photoplethysmography analysis.The ANS-1 SSR module assesses sudomotor function by generating a low-voltage signal with a constant weak direct current (DC) that is fed to the active electrode. DC passes through the polysynaptic reflex, and upon reaching the pre- and post-ganglionic sympathetic sudomotor fibers it increases the skin electrical current in contact with the passive responsive electrode.(Phase 1) The current is sent from the negative to the positive electrode during 30 s. The voltage is positive. (Phase 2) The polarity of the voltage is switched from the positive to negative electrode for the next 30 s. The voltage is negative with no ion, and the peak of voltage is measured. This peak is named Nitric Oxide (NO) Sweat Peak because it reflects the effect of acetylcholine on skin blood flow. (Phase 3) The current is sent from the positive electrode to negative electrode. The voltage is negative. (Phase 4) The polarity of the voltage is switched from the negative to the positive electrode for the next 30 s. The voltage is positive with a higher ion concentration (OH-), and the peak of voltage is measured. This peak is named iSweat Peak because it reflects the second effect of acetylcholine on the sweat glands. The NO Sweat Peak normal range is ≥832 millivolts (mV). The iSweat Peak normal range is ≥1000 mV. The total time of the measurement is 2 min. A recent study found that the ANS-1 SSR module had a sensitivity of 91.4% and a specificity of 79.1% to detect peripheral distal neuropathy symptoms and was correlated  with the CAN score  waveform) to assess cardiac sympathetic nervous system (SNS) function and parasympathetic nervous system (PNS) function. The assessment is first performed at rest by using Heart Rate Variability (HRV) analysis algorithms and subsequently assessed by performing the Cardiac Autonomic Reflex Tests (CART), Valsalva maneuver, deep breathing, and change in posture, which also involve blood pressure measurements , 14. The2 units. The PTG-TP normal range is <406 msec2.In addition, ANS-1 performs a PTG spectral analysis, using Fast Fourier Transforms (FFT) of the total records of the oximeter wave form providing 3 frequencies: high (HF), low (LF), and very low frequencies (VLF). The PTG Total Power (PTG-TP) is the sum of the three surfaces or powers of VLF, LF, and HF expressed in msecr = −0.64, p < 0.0001) [2/microsiemens (msec2/μSi) units. The PTGi normal range is ≥40 V/s, and the PTG VLFi normal range is ≥33 msec2/μSi.Previously, the ANS-1 PTG-TP was compared with insulin resistance measured by the hyperinsulinemic glycemic clamp technique. The spectral analysis marker PTG-TP had a sensitivity of 95.7% and a specificity of 84.4% for identifying insulin resistance and was correlated with insulin sensitivity ( 0.0001) . The PTGFinally, the ANS-1 Cardiometabolic Risk Score (CMRS) is calculated using the following variables: systolic and diastolic blood pressure, body mass index (BMI), HRV, and PTG spectral analysis indicators. Each variable is scored as 0 = normal, 1 = borderline, or 2 = abnormal to calculate the CMRS. The CMRS normal range is <4.r = 0.56, p < 0.001) and was significantly different between type 2 diabetes patients and healthy participants [Our recent study showed that the ANS-1 CMRS and PTGi had significant correlation with a 2-h oral glucose tolerance test (OGTT) for glucose  using manufacturers reagents and following all manufacturer’s instructions for instrument set up and performing the assays. All tests had intra- and inter-assay coefficients of variation <5%.General inflammation was assessed with serum C-reactive protein (CRP), fibrinogen, and homocysteine; key indicators of multiple inflammatory processes. Kidney function was assessed with blood urea nitrogen (BUN) and creatinine levels. Venous blood (one 6 mL EDTA tube) was collected from participants by a certified phlebotomist, and serum was obtained after allowing the blood to clot for 30 min followed by centrifugation at 1500 × Sociodemographic and health history data were collected using questionnaires that inquired about gender, marital status, race/ethnicity, education, income, current and previous medical diagnoses, injuries and hospitalizations, medication and dietary supplement use, sleep, and behaviors such as coffee, alcohol, and tobacco use. A general peripheral neuropathy questionnaire was used to assess the location, onset, provocation, quality, radiation, severity, and temporality of the condition. The SF-36v2™ Health Survey was utilized to provide psychometrically-based physical and mental health summary measures and a preference-based health utility index . It is aData were analyzed using SPSS 24  for Windows. Frequency and descriptive statistics were calculated on all variables. We used Spearman rank correlations between the ANS-1 system variables and the biomarkers. We used one-way analysis of variance to differentiate healthy subjects and retinopathy patients on physical data and biomarkers. We used independent samples t-tests to compare healthy subjects to retinopathy patients on the ANS-1 CMRS variable and the scales on the SF-36. Healthy subjects and retinopathy patients were compared with receiver operating characteristic curves to determine the specificity and sensitivity of the ANS-1 response marker NO Sweat Peak as a potential screening marker of retinopathy. The criterion for statistical significance was α = 0.05.No adverse events were reported during the study with the use of the ANS-1 system or while collecting other information.n = 50 healthy controls and n = 50 patients with retinopathy) were enrolled in the study with analyzable data. Of the retinopathy subjects, 3 had type 1 diabetes and 45 had type 2 diabetes. The retinopathy patients were significantly older, more likely to be Hispanic, and had higher BMI, systolic and diastolic blood pressures, and homocysteine, fibrinogen, BUN, and creatinine levels (see Table Table p < 0.0001), homocysteine , fibrinogen , the CAN score , and HRV Total Power , and it positively correlated with PTGi (ρ = 0.53 p < 0.0001).The ANS-1 response marker NO Sweat Peak inversely correlated with BUN  with an area under the curve (AUC) = 0.81  and an asymptotic significance <0.0001 . The ANS-1 system marker Stress Index and the CAN score correlated with CRP , iSweat Peak correlated with PTG-TP , and PTG VLFi correlated with fibrinogen .The ANS-1 system sudomotor response marker Sweat Peak inversely correlated with the severity of symptoms on the peripheral neuropathy scale  fibrinogen, an indicator of blood clotting, (e) PTGi, a marker of endothelial function, (f) the CAN score, and (g) HRV Total Power, which are markers of autonomic neuropathy. All of these significant findings strongly indicate that NO Sweat Peak is a marker of microvascular disease. Sweat Peak was correlated with the severity of symptoms of peripheral neuropathy. This finding suggests that iSweat Peak is a marker of sweat gland nerve or unmyelinated C fiber dysfunction or damage. Thus, the results of the current study help to support the validity of our assumptions regarding the ANS-1 response markers NO Sweat Peak and iSweat Peak.In the present study, NO Sweat Peak was correlated with: (a) retinopathy, a microvascular disease, (b) BUN, an indicator of kidney function (diabetic nephropathy is a microvascular disease), (c) homocysteine, which indicates a deficiency of vitamin BA paucity of information has been published in the extant literature with other methods of evaluating sudomotor function. Comparing the NO Sweat Peak ability to discriminate microvascular disorders using a sudomotor test, only one other study showed that a galvanic skin response measurement had a lower AUC of 0.65 and 0.68 for the feet and hands, respectively, than NO Sweat Peak (AUC of 0.81) . CompariThe underlying method used by the ANS-1 SSR is based on sudomotor function background and physics. Sudomotor function is primarily mediated by the stimulation of the post-sympathetic cholinergic fibers through the action of acetylcholine. Acetylcholine stimulates the nicotinic muscarinic (M) receptors. The activation of M receptors has 2 effects: (a) Activation of M3 on vascular endothelial cells causes increased synthesis of NO, which diffuses to adjacent vascular smooth muscle cells and causes their relaxation and vasodilation of the vessels that allows an exchange between vessels and sweat glands and facilitates the production of sweat .Therefore, sudomotor dysfunction, defined as decreased sudomotor activity, could be reflective of impaired C fiber function or density (low level or absence of acetylcholine production) or impaired skin microcirculatory vasodilation (low or absence of response to NO) due to endothelial dysfunction. When a constant DC is applied to the human body between two electrodes, the current is carried by ions, ions flow from the negative electrode toward the positive electrode, and the current flow is opposite of the flow of ions. Therefore, the positive polarity corresponds to a higher concentration of ions .Since sweat is 96.4% water, the concentration of hydroxide ions (OH-) at the positive electrode is the same (99.6%) when the current is applied. Activation of IPP causes a calcium influx and movement of negative ions across the apical membrane. However, since OH- and chloride (Cl-) are in competition, the very low concentration of Cl- is not significant and does not affect the measurement, and only the OH- concentration reflects the IPP activation . TherefoThe correlations of the HRV marker Stress Index and CAN score with CRP suggest that autonomic nervous system dysfunction is an inflammatory process, which has been shown previously, as baroreflex sensitivity was inversely correlated with both white blood cell count (WBCC) and CRP, and HRV was independently inversely associated with WBCC . As inflOur discovery that the correlation between the SSR marker Sweat Peak with the PTG-TP marker of insulin resistance suggests that the sweat gland nerve or unmyelinated C fiber function is influenced by insulin production. To our knowledge, the ANS-1 SSR module is the only sudomotor test that can distinguish between microcirculatory and autonomic nervous system disorders in one assessment. Sudomotor dysfunction or decreased activity could be reflective of impaired C fiber function or density (low level or absence of acetylcholine production) or impaired skin microcirculatory vasodilation (low or absence of response to NO) due to endothelial dysfunction . Other sAlthough the early manifestation of microvascular diseases is asymptomatic, eventual sweat gland nerve dysfunction or damage causes chronic pain such as cold, tingling, or burning or a pins and needles sensation . Diabete12 or urine microalbumin to compare to the ANS system markers. The ANS-1 system may be useful in guiding screening for retinopathy and other microvascular dysfunction prior to overt diabetes or cardiovascular disease, but larger scale studies are warranted to substantiate these results and to continue to explore the clinical and prognostic significance of the system.The retinopathy patient group had a greater percentage of Hispanics relative to the healthy control group. We did not correlate the severity of retinopathy  with the ANS system markers. We did not measure vitamin B12 or folic acid deficiency, and (c) the CAN score. We also found elevated CRP and fibrinogen levels in the retinopathy group, suggesting increased inflammation and cardiovascular disease risk. Given the correlations between the HRV marker Stress Index and CAN score with CRP, the ANS-1 system may also prove to be an excellent screening tool for early cardiovascular disease and/or an assessment of cardiovascular risk.The results of the current study showed that the ANS-1 process of measuring SSR by using electrical stimulation with a change of DC flow direction during the exam and showing the peak amplitudes of current at the positive and negative electrodes should be useful for detecting the earliest manifestations of microvascular diseases and sweat gland nerve or unmyelinated C fiber dysfunction. Our study also found that NO Sweat Peak had adequate sensitivity and specificity to distinguish between healthy controls and patients with retinopathy and additionally showed a lower QoL and higher CMRS among the retinopathy patients. NO Sweat Peak was also inversely correlated with: (a) BUN, which estimates kidney functioning, (b) homocysteine, which is an inflammatory marker that is indicative of vitamin B12 is known to improve microcirculation, NO Sweat Peak could be useful in identifying microcirculatory disorders. Thus, it should be considered a microcirculation marker.Since retinopathy and kidney disorders are microvascular diseases, and supplementing with vitamin B12, folic acid, or other anti-inflammatory nutrients or foods. Finally, based on the composite findings of several studies using the ANS-1 markers in 3 continents by detecting (a) insulin resistance and correlating with OGTT and (b) microcirculatory disorders, symptoms of peripheral neuropathy, cardiac autonomic neuropathy, and CAD [Moreover, since NO Sweat Peak, a marker of sudomotor function and microcirculatory disorders, is highly correlated with the CAN score, a marker of autonomic neuropathy, the assumption that a microcirculatory disorder is related to autonomic neuropathy seems to be supported by the results of our study. This finding suggests a new way to prevent and treat autonomic neuropathy by early detection with the ANS-1 system and treatment of microcirculatory disorders with vitamin B and CAD , the ANS


To compare the intravenous Labetalol versus intravenous hydralazine in patients having severe Pregnancy induced hypertension (PIH) and pre eclampsia (PE) in pregnancy.Seventy eight women admitted in the Department of Gynecology and Obstetrics, Civil Hospital Karachi, having severe PIH/PE and fulfilling the inclusion criteria were included in the study. Random selection of patients was performed using sealed opaqe envelop for administration of either intravenous noted (IV) Labetalol or Hydrallazine. The mean fall in the MAP in each group was noted. This data was analyzed by applying SPSS version 13. The study was conducted from November 2012 to April 2013.The mean (±SD) age of the labetalol group was 27.46 (±5.28) years while that in the hydralazine group was 26.28 (±5.17) years. The mean fall in MAP observed in the labetalol group was 29.10 ± 7.21 mmHg and that in the hydralazine group was 25.05 ± 10.15 mmHg which was statistically significant with the p value being 0.046.Intra Venous labetalol lowered MAP more than hydralazine, when administered to pregnant females with severe Pregnancy induced hypertension and pre eclampsia in pregnancy. Hypertensive disorders of pregnancy account for a leading cause of peripartum morbidity and mortality.Recent guidance from the National Institute of Health and Clinical Excellence, UK, recommends inpatient treatment of severe hypertension of pregnancy with labetalol , intravenous hydralazine or oral nifedipine as first line alternative antihypertensives within the critical care setting. For many years hydralazine has been the antihypertensive of choice for women with severe hypertension in pregnancy. Its use was associated with adverse effects. Labetalol is also used to treat acute hypertension in pregnancy as a first line drug. Neonatal bradycardia was the most associated adverse effect of concernThe rationale of the study was to compare the impact of intravenous labetalol and intravenous hydralazine in pregnant patients with severe hypertension in terms of reduction of mean arterial pressure as there is no significant data available in Pakistan on this topic. The results of the study might help to identify a drug which would be expected to give better results to avert maternal and fetal complications.This comparative study was conducted in the department of Obstetrics and Gynecology Dow University of Health Sciences and Civil Hospital Karachi. To compare blood pressure lowering effect of labetalol and Hydralazine, two groups of women were identified, each group consisting of 39 women.The sample size was calculated using formula n=2ZPQ/D. n=minimum sample size, Z=95% confidence interval using 1.96, P=prevalence of severe pre eclampsia 2, Q=1.0-p, D=degree of accuracy desired, usually set at 0.05, n=37 adding 5% attrition rate anticipated response rate 95%. The selected sample size was37/0.95= 38.9. Total of 39 women in each group were taken making a sample size of 78 was calculated.9Non probability sampling technique was used for sample collection. Seventy eight women with pregnancy induced hypertension at a gestational age between 24-37 weeks with a Systolic Blood Pressure of >160mm and Diastolic Blood Pressure > 110 mm were considered fulfilling inclusion criteria and were recruited for study. Pregnant women with medical disorders, situations where these drugs were contra indicated, women with severe bradycardia, history of reaction to these drugs were excluded from the study.Total 78 patients who were admitted in the Obstetrics and Gynecology Department Unit II of Civil Hospital Karachi, and fulfilled the inclusion criteria were enrolled in the study after taking informed consent. A detailed history was taken and the gestational age of the patient was calculated using date of last menstrual period. The patient’s blood pressure was then recorded. With patient sitting comfortably blood pressure was recorded using Mercury monometer. An appropriate cuff size was used. Reading of Systolic and Diastolic blood pressure were taken at Korat coff 1 and V respectively.The patients were then randomly assigned to either of the two groups that is the Labetalol group or the Hydralazine group using sealed opaque envelope method. Once the group of the patient was assigned, an intravenous access was established using cannula of 18 gauge and medication was administered to each group.In this group, 20mg intravenous slow bolus dose of labetalol was administered followed by 40mg if not effective within 20 minutes, followed by 80mg every 20 minutes to a maximum of three doses.In this group, 5mg of hydralazine as a slow bolus was given intravenously, and repeated every 20 minutes until the desired effect was achieved or maximum of three doses. All patients were monitored actively during the whole process including repeated blood pressure readings after every 15 minutes and the general status too was taken in account.Data were entered on a pre-designed performa. Confounding variables were controlled by excluding those patients who had specific contraindications to either labetalol or hydralazine, or had a known allergy to either of the two drugs. All patients who suffered from severe bradycardia were also excluded.The software program SPSS for Windows version 13  was utilized for all statistical analyses. Frequencies and percentages were used to summarize age, parity, and gestational age. Mean ± standard deviation (SD) were computed for numerical variables like age distribution, gestational age, SBP, DBP, number of doses of drugs used and MAP. Stratification was done with regards to age, parity, and gestational age to observe the effects of these on outcomes.was 27.46 years while in hydralazine group it was 26.28 years. The mean parity in labetalol group was 1.92 and hydralazine group was1.95. Mean gestational age in labetalol group was 33.23 and mean gestational age in hydralazine group was 32.97.The mean age of patients in labetalol group Out of 78 patients, 44 (56.4%) required more than one dose of the drug used. Single dose of labetalol was sufficient in reducing the mean arterial pressure (MAP) to the desired level in 20 (51.3%) of the patients. In contrast single dose was sufficient only in 14 (35.9%) patients in the hydralazine group. The mean (±SD) number of doses required in the labetalol group was 1.59 (±0.68) while in the hydralazine group number of doses required was 1.90 (±0.79)At admission of patients the Systolic blood pressure (SBP) in the labetalol group was 172.69±14.1 mmHg while in the hydralazine group it was 172.31±12.24 mmHg. The diastolic blood pressure (DBP) at presentation was 116.67±5.78 mmHg in the labetalol group and 116.15 ± 5.90 mmHg in the hydralazine group. Hence the mean MAP in the former was 134.95 ± 7.10 mmHg and 134.46±6.35 mmHg in the later group.After treatment the mean SBP in the labetalol group was 140.49±8.88 mmHg while in the hydralazine group it was 141.03±8.59 mmHg. The DBP after treatment was 91.03±7.88 mmHg in the labetalol group and 94.49±7.05 mmHg in the hydralazine group. Hence the mean MAP in the former was 107.10±7.19 mmHg and 109.54±7.00 mmHg in the later group.The mean fall in MAP observed in the labetalol group was 29.10 ±7.21 mmHg and that in the hydralazine group was 25.05±10.15 mmHg. On application of independent t test the difference in the fall of MAP in these two groups was statistically significant with the p value being 0.046.Patients in Hydrallazine group had headache and tachycardia more often as compare to women in Labetalol group. Side effects like maternal hypotension, nausea, vomiting, adverse fetal heart rate recording were not noted significantly in either group. Low Apgar score at 5 minutes was not noted which could be attributed to use of these drugsHypertension in pregnancy contributes significantly towards the maternal morbidity and mortality in developed as well as developing world. The gravity of the condition is pronounced in cases of severe hypertension. There is consensus that sustained severe hypertension in pregnancy should be treated as it is considered to be a risk factor for maternal end organ complications such as cerebral stroke. Threshold of blood pressure at which treatment should start is important. At the same time treatment should not cause a marked lowering of blood pressure leading to reduction in utero placental circulation. In a case series Martin et al found 96% of women had a Systolic Blood Pressure of 160mm Hg or above immediately prior to stroke and only 13% had Diastolic Blood pressure of 110 mm Hg or above.13American College of Obstetricians and Gynecologist recommends parenteral labetalol and hydralazine as first line drug for the treatment of acute severe hypertension.Labetalol is a non-selective beta blocker and post synaptic alpha-1blocking agent. Labetalol may be considered as first line drug, but there is a potential risk of fetal bradycardia.Both drugs have been used extensively in the management of pregnant women with higher blood pressure. Trivedi Swati at el. in their comparative study on Labetalol and Hydrallazine found both drugs as effective and quick acting antihypertensive agents in severe pre eclampsia.In a study conducted by Mable et al authors found hydralazine lowered mean arterial pressure more than Labetalol that is 13.3 versus 11.2mm Hg.19Contrary to above findings, in the current study reduction of blood pressure with labetalol was significant with p value of 0.046. This differs from the study of Mable and Ashe.21Magee in his meta-analysis proposed labetalol as a promising alternate as first line agent.Studies reporting the efficacy of hydralazine and labetalol as anti-hypertensive mostly favored null hypothesis demonstrating no superiority of one drug over another in achieving blood pressure reduction. The current study has reported better results in reduction of blood pressure with labetalol as compared to hydralazine. This study contain a sample size of 78 with 39 in each group. A well designed, randomized controlled trial with adequate sample size will help to determine better drug for control of hypertension particularly in context of Pakistani pregnant population.Blood Pressure recordings were not maintained on study proforma after two blood pressure readings. Although American College of Obstetricians and Gynaecologist recommends 10 mg dose of parenteral Hydrllazine, a dose of 5mg of Hydrallazine was preferred due to the fact that women from study population were not over weight.Our results have shown better control of blood pressure with labetalol. Administration of drug during pregnancy and more so in cases of critical situation needs care full judgment. A balance between safety profile of drug and a given dose is of crucial importance. Therefore until conclusive results are obtained regarding superiority of hydralazine or labetalol, choice of drug should be on clinicians experience and discretion.AK: Supervised study, wrote manuscript and is responsible for intellectual integrity of the study.SH: Conducted study, analyzed results.FDN: Arranged references.