Course of blood pressure in mild hypertensives after withdrawal of long term antihypertensive treatment. Medical Research Council Working Party on Mild Hypertension.

A series of 1418 men and 1,347 women with mild hypertension (diastolic phase V 90-109 mm Hg) aged 35-64 who had either had long term antihypertensive treatment with bendrofluazide or propranolol or taken placebo tablets for a similar period were randomly allocated to groups in which their tablets were either stopped or continued. The course of blood pressure and of biochemical variables was followed up for two years. Mean blood pressures rose rapidly after the withdrawal of active treatment, and between nine months and one year after stopping treatment the antihypertensive effect had almost disappeared. The effect persisting longer than this, and possibly due to resetting of the baroreceptors or of other blood pressure control mechanisms, was very small, and as the rise in mean pressure was due to an upward movement in general distribution there was no evidence of a subgroup in whom these mechanisms had been permanently reset to a clinically important extent. After withdrawal of propranolol the rise in pressure was more rapid in younger than in older people. After stopping bendrofluazide pressure rose more rapidly in men who had had higher pressures before and during treatment; this effect was not seen in women. Disturbances in biochemical variables associated with drug treatment had largely resolved by the end of two years after withdrawal. Stopping placebo tablets made no consistent difference to blood pressure.     

Genotype Imputation with Millions of Reference Samples

We present a genotype imputation method that scales to millions of reference samples. The imputation method, based on the Li and Stephens model and implemented in Beagle v.4.1, is parallelized and memory efficient, making it well suited to multi-core computer processors. It achieves fast, accurate, and memory-efficient genotype imputation by restricting the probability model to markers that are genotyped in the target samples and by performing linear interpolation to impute ungenotyped variants. We compare Beagle v.4.1 with Impute2 and Minimac3 by using 1000 Genomes Project data, UK10K Project data, and simulated data. All three methods have similar accuracy but different memory requirements and different computation times. When imputing 10 Mb of sequence data from 50,000 reference samples, Beagle’s throughput was more than 100× greater than Impute2’s throughput on our computer servers. When imputing 10 Mb of sequence data from 200,000 reference samples in VCF format, Minimac3 consumed 26× more memory per computational thread and 15× more CPU time than Beagle. We demonstrate that Beagle v.4.1 scales to much larger reference panels by performing imputation from a simulated reference panel having 5 million samples and a mean marker density of one marker per four base pairs.     

Collaborative care of hypertensives,using a shared record.

A shared hospital-GP record for control of hypertension was studied in a sample of 60 patients. Over 80% of patients brought the record to hospital duly completed. Two-thirds of GPs, and the hospital staff, assessed the record as a useful aid in the care of hypertensives. It is still employed enthusiastically, three years after its introduction.     

Natriuresis and carbohydrate-induced antinatriuresis in fasted, hydrated hypertensives.

After an overnight fast and oral hydration with water, hypertensive subjects developed a significant natriuresis (mean urine sodium excretions increased from 130 to 291 mueq/min. The incidence of a natriuresis (greater than 200 mueq sodium excreted per minute) was 75% in the hypertensive group (16 subjects) compared to 27% in a previously studied normotensive group (22 subjects). The incidence of a carbohydrate-induced antinatriuresis (greater than 30% decrease in urinary sodium excretion) was 62% in the hypertensive group compared to 41% in the normotensive group. No decrease in plasma volume (131I-labeled albumin concentration) due to a shift of solute and water intracellularly could be documented to explain the antinatriuretic effect of glucose. An incidental observation was a significant decrease in plasma zinc concentrations after glucose ingestion.     

Born‐digital biodiversity data: Millions and billions

Given the dramatic pace of change of our planet, we need rapid collection of environmental data to document how species are coping and to evaluate the impact of our conservation interventions. To address this need, new classes of “born digital” biodiversity records are now being collected and curated many orders of magnitude faster than traditional data. In addition to the millions of citizen science observations of species that have been accumulating over the last decade, the last few years have seen a surge of sensor data, with eMammal's camera trap archive passing 1 million photo‐vouchered specimens and Movebank's animal tracking database recently passing 1.5 billion animal locations. Data from digital sensors have other advantages over visual citizen science observation in that the level of survey effort is intrinsically documented and they can preserve digital vouchers that can be used to verify species identity. These novel digital specimens are leading spatial ecology into the era of Big Data and will require a big tent of collaborating organizations to make these databases sustainable and durable. We urge institutions to recognize the future of born‐digital records and invest in proper curation and standards so we can make the most of these records to inform management, inspire conservation action and tell natural history stories about life on the planet.     

Proton NMR study of erythrocytes of essential hypertensives

Proton NMR studies (saturation transfer experiments and longitudinal relaxation time determinations) indicate that substantial differences exist between erythrocytes of essential hypertensives and normotensive subjects. A higher degree of intracellular organization has been found for the hypertensives and several factors are proposed as contributing to the observed behaviour.     

Determinants of platelet activation in hypertensives with microalbuminuria

Microalbuminuria is a predictor of adverse outcome in hypertension. We evaluated in vivo platelet activation, by urinary 11-dehydrothromboxane (TX)B₂ and plasma P-selectin, in hypertensives with or without microalbuminuria, and its possible association with oxidative stress, by urinary 8-iso-prostaglandin (PG)F_2α and endothelial dysfunction. Sixty essential hypertensive patients, with (n = 30) or without (n = 30) microalbuminuria, and 30 controls were studied. Endothelial function was assessed by nitric oxide products, intercellular adhesion molecule (ICAM)-1, and asymmetric dimethylarginine (ADMA) levels. Urinary 11-dehydro-TXB₂ excretion was higher in microalbuminuric (median 805 pg/mg creatinine) compared to nonmicroalbuminuric patients or controls (414 and 291 pg/mg, respectively; P < 0.0001). Plasma P-selectin was significantly higher in patients with microalbuminuria (median 136 ng/ml) as compared to those without microalbuminuria or controls (85 and 65 ng/ml; P < 0.0001). Urinary 8-iso-PGF_2α excretion was also enhanced in microalbuminuric (median 279 pg/mg creatinine) compared to nonmicroalbuminuric patients or controls (157 and 146 pg/mg, respectively; P < 0.0001). A significant impairment in endothelial function was found in microalbuminuric patients, with decreased nitric oxide and increased ICAM-1 and ADMA levels. Multivariate regression analysis showed that urinary 8-iso-PGF_2α excretion (beta = 0.49; P < 0.0001) and microalbuminuria (beta = 0.36; P < 0.001) were independently related to 11-dehydro-TXB₂ in hypertensives. Vitamin E supplementation (900 mg daily for 1 month) in 10 hypertensives with microalbuminuria was associated with normalization in median 11-dehydro-TXB₂ and 8-iso-PGF_2α. We conclude that lipid peroxidation is a major determinant of persistent platelet activation in hypertensive patients with microalbuminuria.     

Confirming the diagnosis of mild hypertension.

Patients with newly found raised blood pressure are known to have lower pressures at subsequent measurements even when not treated. A study was undertaken to determine the extent to which (a) the number of follow-up measurements and (b) the duration of the intervals between them contributed to this fall in pressure. In 42 general practices 110 patients were identified as having for the first time a diastolic pressure (phase V) greater than 90 and less than 110 mm Hg. Both diastolic and systolic pressures were appreciably lower when measured at return visits when compared with the first measurement. The systolic pressure dropped appreciably in the intervals between the first and the second visits and again between the second and third visits. The diastolic pressure fell appreciably only between the first and second visits. The duration of the interval between visits was not associated with a fall in either systolic or diastolic pressure, but the number of measurements was. This pattern of fall in pressure was not affected by the patient''s age or sex. From these results we conclude that patients with newly identified blood pressures that are mildly raised should be seen at two further visits before a decision about treatment is made. The timing of these follow-up visits is not crucial.     

Sympathetic activity and the heterogenous blood pressure response to exercise training in hypertensives.

To test whether changes in sympathetic nervous system (SNS) activity or insulin sensitivity contribute to the heterogeneous blood pressure response to aerobic exercise training, we used compartmental analysis of [3H]norepinephrine kinetics to determine the extravascular norepinephrine release rate (NE2) as an index of systemic SNS activity and determined the insulin sensitivity index (S(I)) by an intravenous glucose tolerance test, before and after 6 mo of aerobic exercise training, in 30 (63 +/- 7 yr) hypertensive subjects. Maximal O2 consumption increased from 18.4 +/- 0.7 to 20.8 +/- 0.7 ml x kg(-1) x min(-1) (P = 0.02). The average mean arterial blood pressure (MABP) did not change (114 +/- 2 vs. 114 +/- 2 mmHg); however, there was a wide range of responses (-19 to +17 mmHg). The average NE2 did not change significantly (2.11 +/- 0.15 vs. 1.99 +/- 0.13 microg x min(-1) x m(-2)), but there was a significant positive linear relationship between the change in NE2 and the change in MABP (r = 0.38, P = 0.04). S(I) increased from 2.81 +/- 0.37 to 3.71 +/- 0.42 microU x 10(-4) x min(-1) x ml(-1) (P = 0.004). The relationship between the change in S(I) and the change in MABP was not statistically significant (r = -0.03, P = 0.89). When the changes in maximal O2 consumption, percent body fat, NE2, and S(I) were considered as predictors of the change in MABP, only NE2 was a significant independent predictor. Thus suppression of SNS activity may play a role in the reduction in MABP and account for a portion of the heterogeneity of the MABP response to aerobic exercise training in older hypertensive subjects.     

Predictors of success in hypertensives treated with biofeedback-assisted relaxation

This paper describes differences in response in seventeen patients with essential hypertension who participated in a treatment program consisting of electromyograph biofeedback assisted relaxation training. Responders were found to have higher treatment values of urinary and plasma cortisol, Trait Anxiety and forehead muscle tension compared to treatment failures. Responders also sustained greater decreases in plasma, and urinary cortisol after treatment. These data are discussed in light of the ability to predict which hypertensive patients may be most benefitted by a relaxation based treatment.