Comparison of thiazide‐like diuretics versus thiazide‐type diuretics: a meta‐analysis

Thiazide diuretics are widely used for the management of hypertension. In recent years, it has been actively debated that there is interchangeability of thiazide‐type diuretics hydrochlorothiazide and thiazide‐like diuretics including indapamide and chlorthalidone for the treatment of hypertension. With the purpose of seeking out the best thiazide diuretic for clinicians, we summarized the existing evidence on the two types of drugs and conducted a meta‐analysis on their efficacy in lowering blood pressure and effects on blood electrolyte, glucose and total cholesterol. Twelve trials were identified: five based on the comparison of indapamide versus hydrochlorothiazide and seven based on the chlorthalidone versus hydrochlorothiazide. In the meta‐analysis of blood pressure reduction, thiazide‐like diuretics seemed to further reduce systolic BP ([95% CI]; ?5.59 [?5.69, ?5.49]; P < 0.001) and diastolic BP ([95% CI]; ?1.98 [?3.29, ?0.66]; P = 0.003). Meanwhile, in the analysis of side effects, the incidence of hypokalemia ([95% CI]; 1.58 [0.80, 3.12]; P = 0.19), hyponatremia ([95% CI]; ?0.14 [?0.57, 0.30], P = 0.54), change of blood glucose ([95% CI];0.13 [?0.16, 0.41], P = 0.39) and total cholesterol ([95% CI]; 0.13 [?0.16, 0.41], P = 0.39) showed that there is no statistical significant differences between the two groups of drugs. In conclusion, using thiazide‐like diuretics is superior to thiazide‐type diuretics in reducing blood pressure without increasing the incidence of hypokalemia, hyponatraemia and any change of blood glucose and serum total cholesterol.     

Auscultatory indirect measurement of blood pressure in dogs

An indirect method of measuring blood pressure (cuff plus stethoscope) was evaluated in 70 dogs weighing 15 to 30 kg (17.5 +/- 8.8 kg; mean +/- standard deviation). A cuff 12 cm wide was used. The measurements were most audible with the cuff on the upper foreleg of the dog and with the stethoscope placed in the medial epicondylar region just distal to the cuff. The cuff was inflated to greater than systolic pressure and allowed to deflate slowly. In 70 lightly sedated dogs, systolic blood pressures averaged 145 +/- 25 mmHg (mean +/- standard deviation) and diastolic blood pressures averaged 84 +/- 14 mmHg. Indirect measurements were compared to direct measurements (femoral arterial catheter). Systolic pressures obtained by this direct method averaged 138 +/- 29 mmHg (mean +/- standard deviation) and diastolic pressures averaged 84 +/- 17 mmHg. The correlation coefficient for systolic pressure was 0.96 and for diastolic pressure 0.97.     

Blood Pressure Measurement under Within-Visit Conditions in Normotensive Volunteers

The dynamics of mean values and blood pressure (BP) variability were studied under within-visit conditions in normotensive subjects. The study involved 104 volunteers aged 20 to 65 years (46 men and 58 women) without the history of hypertension. Nine repeated BP measurements were performed within 35 min in a summer period to determine the final time for the BP decrease, i.e., for the “stabilization” of BP within one visit, and the within-visit BP variability (WVV) expressed as the standard deviation (SD) and the coefficient of variation (CV). The tenth measurement of BP was conducted to assess the effect of physical activity after a 5-min walk followed by a 5-min seated position. In order to study the effect of seasons on the BP variation, 32 volunteers were examined in winter (January–February) and in summer (June–July) of the same year. The within-visit BP in normotensive subjects was characterized by two aspects. The first one associated with a decrease in systolic BP (SBP) and diastolic BP (DBP), on average, by 7 mmHg and up to 2 mmHg, respectively, ended by the 25th minute and was followed by the period of conventional stabilization in mean values. The following two periods were observed in the SBP decrease: a 5-min rapid decrease (1 mmHg/min) and a 20-min slow decrease (0.1 mmHg/min). The dynamics of mean SBP values depended on gender and age. The second aspect is the individual SBP variability, which continued against the stabilization of mean values. The CV of 35-min SBP reached, on average, 4% and was higher in women compared with men. SD was higher in the older age group. The maximum variability was observed within the first 5 min under the investigation. Then, in the periods of slow decrease and stabilization, the variability did not change significantly (not exceeding 3%, on average), despite a significant decrease in the mean SBP values. During a rapid SBP decrease neither of variability indices depended on gender or age. The SD of SBP during the slow decrease and stabilization was higher in the older female group than in the young women, not differing in men of both age categories. After 5 min of rest in a seated position, the consequences of walking for BP were insignificant in normotensive subjects. The dynamics of SBP did not differ in summer and winter of the same year.     

Device-Guided Paced Respiration as an Adjunctive Therapy for Hypertension in Obstructive Sleep Apnea: A Pilot Feasibility Study

Data suggest that device-guided paced respiration (<10 breaths/min) may reduce blood pressure in hypertensive patients. We hypothesized that daily device-guided slow breathing may lower blood pressure in patients with hypertension and obstructive sleep apnea (OSA). In this one-arm pilot study, we enrolled 25 subjects with hypertension and OSA. Subjects were asked to perform device-guided paced respiration 30 min a day for 8 weeks. Our primary outcome was change in office systolic and diastolic blood pressures from baseline to 8 weeks. Twenty-four subjects completed the study. Mean baseline blood pressure was 140.0 ± 10.2 mmHg systolic and 82.7 ± 8.9 mmHg diastolic. Complete device data were available for 17 subjects. Mean device adherence was 81 ± 24% and 51% achieved a mean breath rate ≤10 breaths/min over 8 weeks. Three subjects had changes in their anti-hypertensive medications during the study. Among the remaining 21 subjects, mean difference in office blood pressure from baseline to 8 weeks was −9.6 ± 11.8 mmHg systolic (p ≤ 0.01) and −2.52 ± 8.9 mmHg diastolic (p = 0.21). Device-guided paced respiration may lower systolic blood pressure in patients with hypertension and OSA; however, our findings need to be confirmed with larger randomized controlled trials.     

Effect of stress management on blood pressure in mild primary hypertension.

OBJECTIVE--To establish whether stress management had a larger effect than a control treatment on resting blood pressure, ambulatory blood pressure, and left ventricular mass. DESIGN--A 12 week baseline period of habituation to measurement of blood pressure was followed by randomisation to either stress management or mild exercise for six months and follow up six months later. SETTING--General practice, district general hospital, and medical school. PATIENTS--Of the 184 patients aged under 60 with mild primary hypertension who entered the baseline habituation period, 88 were excluded because they failed to meet the entry criteria or they withdrew from the study. The remaining 46 men and 50 women underwent treatment. INTERVENTIONS--10 clinical sessions and daily practice at home of either stress management based on relaxation or non-aerobic stretching exercises. Mildly stressful 15 minute interviews before and after treatment. MAIN OUTCOME MEASURES--Diastolic and systolic blood pressure in the clinic and during 12 hours of ambulatory recording, and left ventricular mass measured by echocardiography. RESULTS--The patients'' blood pressure fell during habituation (systolic pressure from 152 mmHg to 140 mmHg, diastolic pressure from 98 to 93 mm Hg), but neither resting nor ambulatory blood pressure was changed by the treatments. Left ventricular mass was also unchanged. Blood pressure rose during the stressful interview, but this rise was reduced by stress management (systolic pressure rose by 7.4 mmHg before treatment and by 3.7 mmHg after treatment). CONCLUSION--Stress management of a type advocated for treating mild primary hypertension is ineffective in lowering blood pressure in patients who are well habituated to measuring blood pressure.     

Biomarker response and therapy prediction in renal denervation therapy – the role of MR-proadrenomedullin in a multicenter approach

Background: Renal denervation has been proposed as a therapeutic option in patients with resistant hypertension. Circulating blood borne biomarkers might be helpful to identify individuals responding to RDN therapy. MR-proADM is a strong prognostic marker in patients with cardiovascular disease. The aim of this multicenter study was to evaluate the effect of RDN on MR-proADM concentrations.

Methods and results: We measured MR-proADM, BNP, and MR-proANP in 110 patients before and after RDN in a multicenter setting. All patients were followed up after 1 and 6 months by office and ambulatory blood pressure (BP) measurements. The mean office BP decreased from 165/89 to 152/87?mmHg 6 months after RDN (systolic: p?<?0.001; diastolic: ns), the responder-rate was 74%. Intriguingly MR-proADM concentrations increased from 0.66 to 0.69?nmol/L (p?<?0.001) and were significantly associated with reduction of systolic office BP after 6 months in multivariate analyses (coefficient ?0.0018, p?<?0.001). In therapy-responders MR-proADM concentrations showed a significantly higher increase over time (coefficient 0.0105, p?<?0.05), as compared to non-responders. There were no significant differences in BP change for individuals with low and high baseline MR-proADM (BP-Delta low MR-proADM ?23/?4?mmHg vs. high MR-proADM ?24/?5?mmHg). The natriuretic biomarkers BNP and MR-proANP did not change significantly after 6 months. Biomarkers at baseline were not able to predict for therapy-responder.

Conclusion: In patients undergoing RDN, baseline measurements of various biomarkers had no prognostic use for therapy success in this short time follow-up period in a multicenter approach. Intriguingly, MR-proADM showed a significant association with BP reduction after 6 months.     

Does nitric oxide buffer arterial blood pressure variability in humans?

Animal studies suggest that nitric oxide (NO) plays an important role in buffering short-term arterial pressure variability, but data from humans addressing this hypothesis are scarce. We evaluated the effects of NO synthase (NOS) inhibition on arterial blood pressure (BP) variability in eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). Systemic NOS was blocked by intravenous infusion of N(G)-monomethyl-L-arginine (L-NMMA). Electrocardiogram and beat-by-beat BP in the finger (Finapres) were recorded continuously for 6 min, and brachial cuff BP was recorded before and after L-NMMA in each body position. BP and R-R variability and their transfer functions were quantified by power spectral analysis in the low-frequency (LF; 0.05-0.15 Hz) and high-frequency (HF; 0.15-0.35 Hz) ranges. L-NMMA infusion increased supine BP (systolic, 109 +/- 4 vs. 122 +/- 3 mmHg, P = 0.03; diastolic, 68 +/- 2 vs. 78 +/- 3 mmHg, P = 0.002), but it did not affect supine R-R interval or BP variability. Before L-NMMA, HUT decreased HF R-R variability (P = 0.03), decreased transfer function gain (LF, 12 +/- 2 vs. 5 +/- 1 ms/mmHg, P = 0.007; HF, 18 +/- 3 vs. 3 +/- 1 ms/mmHg, P = 0.002), and increased LF BP variability (P < 0.0001). After L-NMMA, HUT resulted in similar changes in BP and R-R variability compared with tilt without L-NMMA. Increased supine BP after L-NMMA with no effect on BP variability during HUT suggests that tonic release of NO is important for systemic vascular tone and thus steady-state arterial pressure, but NO does not buffer dynamic BP oscillations in humans.     

Blood Pressure Variability and Cardiovascular Risk in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects.     

Biofeedback of R-wave-to-pulse interval normalizes blood pressure

We investigated whether biofeedback of the R-wave-to-pulse interval, a measure related to the pulse wave velocity, enables participants with either high or low arterial blood pressure to modify their blood pressure. Twelve participants with high blood pressure (mean systolic blood pressure = 142.6 ± 13.5 mmHg; mean diastolic blood pressure = 99.9 ± 12.3 mmHg) and 10 participants with low blood pressure (mean systolic blood pressure = 104.8 ± 6.6 mmHg; mean diastolic blood pressure = 73.2 ± 4.2 mmHg) received 3 individual sessions of RPI biofeedback within a 2-week period. Participants with high blood pressure were rewarded for decreasing and participants with low blood pressure for increasing their blood pressure. Standard arm-cuff blood pressure measurements across the sessions served as dependent variables. Participants with high blood pressure achieved significant reductions of systolic (15.3 mmHg) and diastolic (17.8 mmHg) blood pressure levels from the beginning of the first to the end of the last training session. In contrast, participants with low blood pressure achieved significant increases in systolic (12.3 mmHg) and diastolic (8.4 mmHg) blood pressure levels. The degree of blood pressure changes in this study might be of clinical relevance. With prolonged and refined training regimens, even larger effects seem to be likely.     

Comparison of effects of exercise and diuretic on left ventricular geometry, mass, and insulin resistance in older hypertensive adults

To compare the effects of exercise training and hydrochlorothiazide on left ventricular (LV) geometry and mass, blood pressure (BP), and hyperinsulinemia in older hypertensive adults, we studied 28 patients randomized either to a group (age 66.4 +/- 1.3 yr; n = 16) that exercised or to a group (age 65.3 +/- 1.2 yr; n = 12) that received hydrochlorothiazide for 6 mo. Endurance exercise training induced a 15% increase in peak aerobic power. The reduction in systolic BP was twofold greater with thiazide than with exercise (26.6 +/- 12.2 vs. 11.5 +/- 10.9 mmHg). Exercise and thiazide reduced LV wall thickness, LV mass index (14% in each group), and the LV wall thickness-to-radius ratio (h/r) similarly (exercise: before 0.48 +/- 0.2, after 0.42 +/- 0.01; thiazide: before 0.47 +/- 0.04, after 0.40 +/- 0.04; P = 0.017). The reductions in systolic BP and h/r were correlated in the exercise group (r = 0.70, P = 0.005) but not in the thiazide group. Exercise training reduced glucose-stimulated hyperinsulinemia (before: 13.65 +/- 2.6 vs. 9.84 +/- 1.5 mU.ml(-1).min; P = 0.04) and insulin resistance. Thiazide did not affect plasma insulin levels. The results suggest that although exercise is less effective in reducing systolic BP than thiazide, it can induce regression of LV hypertrophy similar in magnitude to thiazide. Unlike hydrochlorothiazide, exercise training can improve insulin resistance and aerobic capacity in older hypertensive people.     

1461名老年患者血压波动与颈动脉斑块形成关系的研究

目的：除了血压水平的高低以外,血压波动也是造成人体靶器官损伤的独立危险因素。本研究以老年男性人群为研究对象,观察血压波动（BPV）与颈动脉斑块形成的关联性。方法：本研究选用1461名患有动脉硬化的老年男性患者为研究对象,将入选对象分为：非颈动脉斑块组和颈动脉斑块组,根据24小时动态血压测定（ABPM）中收缩压（SBP）、舒张N（DBP）的数据,用”个体血压波动法”测定每个患者的血压波动,分析探讨血压波动与颈动脉斑块形成之间的关联性。结果：①颈动脉斑块的形成与24小时收缩期血压波动（SBPV）密切相关（8-3±2．1mmHgVS7．9士2．0mmHg;P〈0．001）,其中与白昼（6：00．22：00）SBPV有关（8．1±2．1mmHgVS7．7土2．1mmHg：P〈0．001）,而与夜间（22：00-6：00）SBPV关系不明显（8,9±3．8mmHgVS8,6±3．7mmHg;P〉0．05）。②与24小时舒张期血压波动（DBPV）有关（5．6±1．4mmHgVS5．4±1．4mmHg;P〈0．05）,其中与白昼（6：00．22：00）舒张期血压波动有关（5．4±1．4mmHgVS5．2士1．4mmHg;P〈0．05）,而与夜间舒张期血压波动无关（6．2±2．7mmHgVS5．9±2．5mmHg;P〉0．05）。结论：在老年男性人群中,颈动脉斑块的形成与收缩期和舒张期血压波动均有关系,主要表现在白昼血压波动。     

Association between light exposure at night and nighttime blood pressure in the elderly independent of nocturnal urinary melatonin excretion

Circadian misalignment between internal and environmental rhythms dysregulates blood pressure (BP) variability because of disruption of the biological clock, resulting in increased nighttime BP. Although exposure to light-at-night is associated with the circadian misalignment, it remains unclear whether exposure to light-at-night in home settings is associated with nighttime BP. In this cross-sectional analysis of 528 elderly individuals (mean age: 72.8 years), we measured bedroom light intensity at 1-min intervals on two consecutive nights along with ambulatory BP, overnight urinary melatonin excretion and actigraphy. With regard to adjusted mean comparisons using analysis of covariance, the light-at-night group (average: ≥5?lux; n?=?109) showed significantly higher nighttime systolic BP (SBP; adjusted mean: 120.8 vs. 116.5?mmHg, p?=?0.01) and diastolic BP (70.1 vs. 67.1?mmHg, p?<?0.01) compared with the Darker group (average: <5?lux; n?=?419) independently of potential confounding factors including overnight urinary melatonin excretion and actigraphic sleep quality. We observed consistent associations between light-at-night and nighttime BP in different cutoff values for light-at-night intensity (i.e. 3 and 10?lux). In conclusion, exposure to light-at-night in home settings is significantly associated with increased nighttime BP in elderly individuals independently of overnight urinary melatonin excretion. A 4.3?mmHg increase in nighttime SBP is associated with a 6.1% increase in total mortality, which corresponds to approximately 10?000 annual excess deaths in Japanese elderly population.     

Inbreeding and the genetic complexity of human hypertension

Considerable uncertainty exists regarding the genetic architecture underlying common late-onset human diseases. In particular, the contribution of deleterious recessive alleles has been predicted to be greater for late-onset than for early-onset traits. We have investigated the contribution of recessive alleles to human hypertension by examining the effects of inbreeding on blood pressure (BP) as a quantitative trait in 2760 adult individuals from 25 villages within Croatian island isolates. We found a strong linear relationship between the inbreeding coefficient (F) and both systolic and diastolic BP, indicating that recessive or partially recessive quantitative trait locus (QTL) alleles account for 10-15% of the total variation in BP in this population. An increase in F of 0.01 corresponded to an increase of approximately 3 mm Hg in systolic and 2 mm Hg in diastolic BP. Regression of F on BP indicated that at least several hundred (300-600) recessive QTL contribute to BP variability. A model of the distribution of locus effects suggests that the 8-16 QTL of largest effect together account for a maximum of 25% of the dominance variation, while the remaining 75% of the variation is mediated by QTL of very small effect, unlikely to be detectable using current technologies and sample sizes. We infer that recent inbreeding accounts for 36% of all hypertension in this population. The global impact of inbreeding on hypertension may be substantial since, although inbreeding is declining in Western societies, an estimated 1 billion people globally show rates of consanguineous marriages >20%.     

A-002 (Varespladib), a phospholipase A2 inhibitor, reduces atherosclerosis in guinea pigs

Background

High blood pressure (BP) is now an important public health problem in non-industrialised countries. The limited evidence suggests ethnic inequalities in BP in adults in some non-industrialised countries. However, it is unclear whether these ethnic inequalities in BP patterns in adults reflect on adolescents. Hence, we assessed ethnic differences in BP, and the association of BP with body mass index (BMI) among adolescents aged 12–17 years in Paramaribo, Suriname.

Methods

Cross-sectional study with anthropometric and blood pressure measurements. A random sample of 855 adolescents (167 Hindustanis, 169 Creoles, 128 Javanese, 91 Maroons and 300 mixed-ethnicities) were studied. Ethnicity was based on self-reported ethnic origin.

Results

Among boys, Maroons had a lower age- and height-adjusted systolic BP than Creoles, and a lower diastolic BP than other ethnic groups. However, after further adjustment for BMI, only diastolic BP in Maroons was significantly lower than in Javanese (67.1 versus 70.9 mmHg). Creole boys had a lower diastolic BP than Hindustani (67.3 versus 70.2 mmHg) and Javanese boys after adjustment for age, height and BMI. Among girls, there were no significant differences in systolic BP between the ethnic groups. Maroon girls, however, had a lower diastolic BP (65.6 mmHg) than Hindustani (69.1 mmHg), Javanese (71.2 mmHg) and Mixed-ethnic (68.3 mmHg) girls, but only after differences in BMI had been adjusted for. Javanese had a higher diastolic BP than Creoles (71.2 versus 66.8 mmHg) and Mixed-ethnicity girls. BMI was positively associated with BP in all the ethnic groups, except for diastolic BP in Maroon girls.

Conclusion

The study findings indicate higher mean BP levels among Javanese and Hindustani adolescents compared with their African descent peers. These findings contrast the relatively low BP reported in Javanese and Hindustani adult populations in Suriname and underscore the need for public health measures early in life to prevent high BP and its sequelae in later life.     

The Effect of Chance Variability in Blood Pressure Readings on the Decision Making of General Practitioners: An Internet-Based Case Vignette Study

Background

Guidelines for the management of blood pressure (BP) in primary care generally suggest that decisions be made on the basis of specific threshold values (e.g. BP 140/90 mmHg); but this fails to adequately accommodate a common cause of variation – the play of chance.

Objective

To determine the impact of chance variability in BP readings on the clinical decision making of general practitioners (GPs) regarding anti-hypertensive treatment and cardiovascular risk management.

Method

We used an internet based study design, where 109 GPs were assigned to manage one of eight case vignettes (guidelines would recommend treatment for only one of the eight) and presented with blood pressure readings that were randomly selected from an underlying population.

Results

Seventeen (15.6%, 17/109) GPs consulted the vignette for whom treatment was recommended, but only 7/17 (41.2%) GPs prescribed treatment, whereas 14/92 (15.2%) GPs prescribed medication to the other vignettes. When deciding to follow-up a vignette GPs were influenced by threshold values for systolic and diastolic BP, but not by the overall cardiovascular risk. If the first reading was a low BP (systolic <140, diastolic <90) GPs were highly likely to discharge the vignette and follow-up a high BP reading (diastolic >90 or systolic BP≥140). Similar factors predicted the decision to prescribe a drug, although the vignette’s cardiovascular risk (>20%) was now statistically significant (p = 0.03).

Conclusions

GP decision making, whilst generally consistent with guidelines, appears to be compromised by chance variation leading to under and over treatment. Interventions to adequately accommodate chance variability into clinical decision making are required.     

Systolic and diastolic blood pressures as predictors of coronary heart disease mortality in the Whitehall study.

Systolic and diastolic blood pressures were compared as predictors of death due to coronary heart disease using data on the 10 year mortality outcome from the 18 403 male civil servants, aged 40-64, in the Whitehall study. There were 727 deaths due to coronary heart disease. At entry to the study the systolic pressure in these men was significantly higher than the diastolic pressure, and a standardised index of relative risk for death from coronary heart disease was greater for systolic blood pressure. After adjustment for age the top quintile of systolic pressure (greater than 151 mm Hg) identified 5% more men at risk of death from coronary heart disease than for the top diastolic quintile (greater than 95 mm Hg). The findings suggested that clinicians should pay more attention to systolic levels as a criterion for making diagnostic and therapeutic decisions.     

Blood pressure response to standing in the diagnosis of autonomic neuropathy: the EURODIAB IDDM Complications Study

Autonomic neuropathy is associated with poor prognosis. Cardiovascular reflexes are essential for the diagnosis of autonomic nerve dysfunction. Blood pressure response to standing is the most simple test for the evaluation of sympathetic integrity, however it is still discussed which diagnostic criteria of abnormal response should be considered as optimal. The EURODIAB IDDM Complications Study involved the examination of randomly selected Type 1 diabetic patients from 31 centres in 16 European counties. Data from 3007 patients were available for the present evaluation. Two tests of autonomic function (response of heart rate /R-R ratio/ and blood pressure from lying to standing) just as the frequency of feeling faint on standing up were assessed. R-R ratio was abnormal in 24% of patients. According to different diagnostic criteria of abnormal BP response to standing (>30 mmHg, >20 mmHg, and >10 mmHg fall in systolic BP), the frequency of abnormal results was 5.9%, 18% and 32%, respectively (p < 0.001). The frequency of feeling faint on standing was 18%, thus, it was identical with the prevalence of abnormal blood pressure response to standing when >20 mmHg fall in systolic blood pressure was considered as abnormal. Feeling faint on standing correlated significantly with both autonomic test results (p < 0.001). A fall >20 mmHg in systolic blood pressure after standing up seems to be the most reliable criterion for the assessment of orthostatic hypotension in the diagnosis of autonomic neuropathy in patients with Type 1 diabetes mellitus.     

Effects of one-year swimming training on blood pressure and insulin sensitivity in mild hypertensive young patients

Swimming is a lifestyle intervention recommended by many clinicians in the prevention and treatment of hypertension. Yet, not all studies have agreed that swimming training can reduce blood pressure (BP). Inclusion of normotensive subjects could be a confounder for discrepancies among studies. In this one-year longitudinal study, long-term effects of swimming training on BP were investigated in 7 mild hypertensive patients (systolic BP (SBP) > 140 mmHg) and 16 normotensive controls. At baseline, these subjects (aged 21.5 +/- 0.1 years) did not participate in any form of sport training activity for the previous 3 months before enrollment into the training program. The training distance progressed from 0 (baseline) to 7 kilometers per week. BP and the homeostasis model assessment for insulin resistance (HOMA-IR) were determined under fasted condition at baseline and 48 h after the last swimming bout. The hypertensive patients displayed significantly greater HOMA-IR than age-matched normotensive controls. When data of all subjects were pooled, plasma glucose concentration was only slightly lowered after training, but weight, height, body mass index, SBP, diastolic BP (DBP) and HOMA-IR values were not significantly altered. However, when observation was restricted to the hypertensive patients, swimming training significantly lowered SBP by approximately 17 mmHg, concurrent with 41% reduction in HOMA-IR. Intriguingly, SBP in the normotensive subjects was elevated by approximately 6 mmHg after training. CONCLUSIONS: The present study found normalization rather than universal reduction effect of swimming training on BP. Furthermore, the BP-lowering effect of training in hypertensive patients appears to be associated with improvement in insulin sensitivity.     

Assessment of central haemomodynamics from a brachial cuff in a community setting

ABSTRACT: BACKGROUND: Large artery stiffening and wave reflections are independent predictors of adverse events. To date, their assessment has been limited to specialised techniques and settings. A new, more practical method allowing assessment of central blood pressure from waveforms recorded using a conventional automated oscillometric monitor has recently been validated in laboratory settings. However, the feasibility of this method in a community based setting has not been assessed. METHODS: One-off peripheral and central haemodynamic (systolic and diastolic blood pressure (BP) and pulse pressure) and wave reflection parameters (augmentation pressure (AP) and index, AIx) were obtained from 1,903 volunteers in an Austrian community setting using a transferfunction like method (ARCSolver algorithm) and from waveforms recorded with a regular oscillometric cuff. We assessed these parameters for known differences and associations according to gender and age deciles from <30 years to >80 years in the whole population and a subset with a systolic BP < 140 mmHg. RESULTS: We obtained 1,793 measures of peripheral and central BP, PP and augmentation parameters. Age and gender associations with central haemodynamic and augmentation parameters reflected those previously established from reference standard non-invasive techniques under specialised settings. Findings were the same for patients with a systolic BP below 140 mmHg (i.e. normotensive). Lower values for AIx in the current study are possibly due to differences in sampling rates, detection frequency and/or averaging procedures and to lower numbers of volunteers in younger age groups. CONCLUSION: A novel transfer-function like algorithm, using brachial cuff-based waveform recordings, provides robust and feasible estimates of central systolic pressure and augmentation in community-based settings.     

Estimating Antihypertensive Effects of Combination Therapy in an Observational Study Using Marginal Structural Models

The evaluation of the antihypertensive effect of multiple antihypertensive drugs using data from an observational study requires adjustment for time‐dependent confounders. Marginal structural models (MSMs) have been proposed to address this type of confounding through inverse probability weighting. Generally, the probabilities are estimated using logistic regression models that assume linearity between the logistic link and the predictors, but the linearity might be inaccurate. In this article, we proposed MSMs to assess the blood pressure‐lowering effects of combination therapy with olmesartan medoxomil (OLM) plus calcium channel blockers (CCB) (OLM+CCB) in an observational study of OLM, and extended estimation methods of the probabilities for the MSMs using generalized additive models (GAMs). The estimation using GAMs was suggested to improve the balance of the distributions of confounder values between the therapy groups in the pseudo‐population. We obtained estimated changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) for OLM+CCB combination therapy after 12 wk compared with OLM monotherapy of ?4.3 mmHg (95% confidence interval (CI): ?7.7 and ?0.9 mmHg) and ?2.9 mmHg (95% CI: ?5.1 and ?0.7 mmHg), respectively. The estimated target BP (SBP<140 mmHg and DBP<90 mmHg) achievement rates for OLM+CCB combination therapy and OLM monotherapy were 62.0 and 46.7%, respectively. The results of the MSMs were closer to those in the randomized controlled trial, such as the combination of OLM and amlodipine besylate in controlling high blood pressure study, than those of conventional methods. The proposed MSMs provided useful information to evaluate the effects of combination therapy of antihypertensive drugs in the context of an observational study.