Lighten UP! A Community-Based Group Intervention to Promote Eudaimonic Well-Being in Older Adults: A Multi-Site Replication with 6 Month Follow-Up.

Objectives: Eudaimonic well-being (EWB), increasingly recognized as a critical component of health, typically declines in later life, and there are no existing programs to sustain or increase EWB in older adults. Lighten UP! is an 8-week program to promote EWB through facilitated group sessions in community settings and at-home practice. Building on earlier pilot research, the current study assessed the effect of the Lighten UP! Program using a longitudinal, multi-site design. Methods: Men and women (N = 169) aged 60 and over were recruited from three Wisconsin communities. EWB, life satisfaction, depression, and diverse aspects of health were assessed before and after the program and at 6-month follow up. Results: Participants reported significantly increased EWB; these changes were maintained 6 months later. The specific EWB domains of self-acceptance, positive relations, and personal growth showed the most robust gains. Participants also showed significant and sustained declines in depressive symptoms, anxiety, and hostility. Conclusions: Lighten UP! Program confirmed its positive effects for enhancing EWB in older adults living in multiple community settings. Clinical Implications: Programs that sustain or enhance EWB in older adults can be expected to yield improvements in diverse aspects of mental and physical health.

Evaluation of a novel cricothyroidotomy introducer in a simulated obese porcine model: a randomised crossover comparison with scalpel cricothyroidotomy.

The Difficult Airway Society 2015 guidelines for management of unanticipated difficulties in tracheal intubation in adults have generated much discussion regarding Plan D: emergency front-of-neck access with a scalpel-bougie cricothyroidotomy technique. There is concern that this technique may not provide an adequate pathway for the bougie and subsequently the tracheal tube, especially in obese patients with deeper airway structures. This could lead to the formation of a false passage, trauma and failure. A novel cricothyroidotomy introducer, 8 mm wide and 170 mm long, with a sharp leading edge and guiding channel to pass a bougie into the trachea, has been designed to complement the scalpel cricothyroidotomy technique. A comparison study of the use of this novel introducer with the scalpel technique in a simulated obese porcine laryngeal model demonstrated shorter insertion times (median (IQR [range]) 85 (65-123 [48-224]) s vs. 84 (72-184 [46-377]) s, p = 0.030). All 26 (100%) participants successfully performed cricothyroidotomy in the introducer group, whereas only 24 (92%) participants were successful in the scalpel group. The introducer group required fewer attempts to access the trachea compared with the scalpel group (p = 0.046). False passages occurred eight (31%) times in the introducer group compared with 17 (65%) times in the scalpel group (p = 0.022). There were no statistical differences in tracheal trauma (p = 0.490), ease of use (p = 0.220) and device preference (p = 0.240). This novel cricothyroidotomy introducer has shown promising results in securing the airway in an emergency front-of-neck access situation. With robust training, this introducer could potentially be complementary to the scalpel-bougie cricothyroidotomy technique.

Cerebrospinal fluid opening pressure: The effect of body mass index and body composition.

OBJECTIVES: Idiopathic intracranial hypertension (IIH) is strongly related to obesity. The relationship between intracranial pressure, body mass index (BMI), percentage body fat and distribution of body fat in non-IIH patients remains less clear. The aim of this study was to examine the relationship between intracranial pressure and body type in non-IIH patients. PATIENTS AND METHODS: Lumbar puncture manometry was used to measure cerebrospinal fluid opening pressure (CSFOP). BMI, in addition to neck, waist and hip circumferences were calculated. Air displacement plethysmography (BODPOD) was used to assess body composition. RESULTS: Data was collected from 100 subjects. 11 subjects with conditions known to cause raised intracranial pressure were excluded from analysis. According to Pearson correlation factors displaying a significant relationship with CSFOP included: BMI (R = 0.635, p < 0.0001); waist circumference (R = 0.498, p < 0.0001), hip circumference (R = 0.513, p < 0.0001) and percentage body fat (R = 0.435, p < 0.001). Multivariate analysis indicated that BMI was the only independent factor which predicted CSFOP. Sub-analysis according to gender indicated that BMI was predictive in females and percentage body fat was predictive in males. We did not identify any differences in BMI, percentage body fat or distribution of body fat in 7 IIH patients and 7 wt-matched non-IIH patients. CONCLUSION: BMI and percentage body fat both positively correlated with CSFOP, but BMI was more predictive in women and percentage body fat was more predictive in men. We did not find a relationship between distribution of body fat and CSFOP.

Randomised trial of flush saphenofemoral ligation for primary great saphenous varicose veins.

OBJECTIVES: The aim of this study was to assess different techniques of saphenofemoral ligation in the treatment of primary varicose veins. METHODS: One hundred and eighty-two patients (210 legs) with primary saphenofemoral junction incompetence were randomised to standard saphenofemoral ligation (transfixion with an absorbable suture) (SSL) or flush saphenofemoral ligation (oversewing with 4/0 polypropylene) (FSL). All legs underwent additional great saphenous vein stripping and multiple phlebectomies. Patients underwent assessment preoperatively, and at 6 weeks, 1 year and 2 years postoperatively with clinical examination, duplex imaging and completion of the Aberdeen Varicose Vein Symptom Severity Score (AVVSSS). RESULTS: A total of 148 patients (172 legs) attended follow-up at 2 years postoperatively. Recurrent varicose veins were visible in 30 legs (33 per cent) in the SSL group and 26 legs (32 per cent) in the FSL group (P=0.90). Neovascularisation was present in 20 groins (22 per cent) in the SSL group and 15 groins (19 per cent) in the FSL group (P=0.57). Nine cases of neovascularisation in the SSL group and five in the FSL group directly resulted in clinical recurrence (P=0.37). CONCLUSIONS: Flush ligation of the saphenofemoral junction confers no advantage over standard ligation with respect to clinical recurrence and neovascularisation. REGISTRATION NUMBER: ISRCTN20235689 (http://www.controlled-trials.com).

Diabetic retinopathy and socioeconomic deprivation in Gloucestershire.

OBJECTIVES: To investigate socioeconomic variations in diabetes prevalence, uptake of screening for diabetic retinopathy, and prevalence of diabetic retinopathy. METHODS: The County of Gloucestershire formed the setting of the study. A cross-sectional study of people with diabetes was done on a countywide retinopathy-screening database. Diabetes prevalence with odds ratios, uptake of screening, prevalence of any retinopathy and prevalence of sight-threatening retinopathy at screening were compared for different area deprivation quintiles. Logistic regression was used to adjust for confounding. RESULTS: With each increasing quintile of deprivation, diabetes prevalence increased (odds ratio 0.84), the probability of having been screened for diabetic retinopathy decreased (odds ratio 1.11), and the prevalence of sight-threatening diabetic retinopathy among screened patients increased (odds ratio of 0.98), while the prevalence of non-sight-threatening diabetic retinopathy remained unchanged with each increasing quintile of deprivation. CONCLUSION: Sight-threatening diabetic retinopathy was associated with socioeconomic deprivation, but non-sight-threatening diabetic retinopathy was not. Uptake of screening was inversely related to socioeconomic deprivation.

The nature of local recurrence after colorectal cancer resection.

OBJECTIVE: Local recurrence (LR) after rectal cancer resection has long been regarded as a particular problem, its incidence having been high. This study aims to determine the reasons why. METHOD: A prospective record was kept of all 887 cases of colorectal adenocarcinoma referred to one surgeon between 1989 and 2000. Of these, 802 underwent major resection. They were followed up for 5 years or until death. RESULTS: There was no significant difference between LR rates throughout the colorectum (P = 0.74). LR was significantly related to tumour grade (P < 0.001) and to tumour stage (P < 0.001), but not to the need to resect involved adjacent structures (P = 0.08), nor, after restorative rectal resection, to the distal margin of clearance (P = 0.97). A difference became apparent between recurrence resulting from tumour left in or implanted into the operation field and tumour resulting from pre-excision metastasis, here called, respectively, technique-related (TLR) and pre-excision metastatic (MLR) local recurrence. MLR was significantly related to tumour stage (P < 0.001), while TLR was not. Some TLR can be curatively excised. CONCLUSION: Rectal LR is no more common than colonic LR. There may be practical merit in discriminating between TLR and MLR.

Comparison of different methods of risk stratification in urgent and emergency surgery.

BACKGROUND: The aim was to compare a number of risk scoring systems prospectively in a cohort of patients who underwent non-elective surgery. METHODS: This was a cohort study of 2349 consecutive patients who had urgent or emergency surgery in a district general hospital in the UK. All patients were scored prospectively using the Revised Goldman Cardiac Risk Index (RGCRI), Portsmouth modification of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM), Surgical Risk Score (SRS) and Biochemistry and Haematology Outcome Models (BHOM). Actual 30-day and 1-year survival rates were compared with the predicted outcomes using receiver-operator characteristic (ROC) curves and Hosmer-Lemeshow analysis. RESULTS: Some 141 patients (6.0 per cent) died within 30 days of operation. This increased to 254 (10.8 per cent) by 1 year. The area under the ROC curve for death within 30 days was 0.90 for P-POSSUM, 0.85 for SRS, 0.84 for BHOM and 0.73 for RGCRI. Only the first three risk scores were able to discriminate accurately within the groups (area under ROC curve over 0.8), with no significant variation between expected and observed mortality rates confirmed by Hosmer-Lemeshow analysis. Similar results were found for the ability of each score to predict outcome at 1 year. CONCLUSION: P-POSSUM, SRS and BHOM scoring systems were all able to predict outcome after emergency and urgent surgery, but the SRS had the advantage of ease of calculation. BHOM requires only the most commonly available blood test data and the computer holding these data can easily perform the calculation.

The effects of commonly prescribed drugs in patients with Alzheimer's disease on the rate of deterioration.

BACKGROUND: Prescribed drugs in patients with Alzheimer's disease may affect the symptomatic progression of their disease, both positively and negatively. AIM: To examine the effects of drugs on the progression of disease in a representative group of patients with Alzheimer's disease. METHODS: Patients with the diagnosis of probable Alzheimer's disease were recruited from the community. The prescribed drugs taken by 224 patients (mean age 82.3 years) were recorded at initial assessment and then correlated in logistic regression analysis with progression of the disease, defined as an increase of one point or more in the Global Deterioration Scale over the next 12-month period. RESULTS: Patients who were taking antipsychotic drugs and sedatives had a significantly higher risk of deterioration than those who were taking none (odds ratios (ORs) 2.74 (95% confidence interval (CI) 1.17 to 6.41) and 2.77 (95% CI 1.14 to 6.73), respectively). Higher risk of deterioration was observed in those who were taking both antipsychotic and sedative drugs together (OR 3.86 (95% CI 1.28 to 11.7). Patients taking drugs licensed for dementia, drugs affecting the renin-angiotensin system and statins had a significantly lower risk of deterioration than those who were not taking any of these drugs (ORs 0.49 (95% CI 0.25 to 0.97), 0.31 (95% CI 0.11 to 0.85) and 0.12 (95% CI 0.03 to 0.52), respectively). CONCLUSION: Our findings have implications for both clinicians and trialists. Most importantly, clinicians should carefully weigh any potential benefits of antipsychotics and benzodiazepines, especially in combination, against the risk of increased decline. Researchers need to be aware of the potential of not only licensed drugs for dementia but also drugs affecting the renin-angiotensin system and statins in reducing progression in clinical trials.

Proteome-based plasma biomarkers for Alzheimer's disease.

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.

Urinary catheterization in care homes for older people: self-reported questionnaire audit of catheter management by care home staff.

A self-administered questionnaire was used to determine care home staff's reported knowledge of the urinary catheter care standards published by the National Institute for Clinical Excellence (NICE) and the Association of Continence Care, and to see whether this differed in homes with higher catheterization rates. Seven hundred and fifty out of 1438 (52%) nursing and care staff from 37 randomly selected care homes with high, medium and low catheterization rates responded. There was no difference in reported practice in care homes in the three health districts sampled or those with differing catheterization rates. Eighty-three percent of the nursing staff and 40% of the other care staff received formal catheter care training. However, at least 10% of all staff reported not washing their hands before handling a catheter, and delaying emptying a urine bag until it was full, rather than three-quarters full. Only 45% of nursing staff and 40% of other care staff encouraged residents to empty their own catheter bags. Routine use of catheter maintenance solutions or bladder washouts was reported by 50% of all staff. Nursing staff (29%) and other care staff (54%) took urine specimens from the catheter bag tap. Compliance with standards has improved greatly since an audit in 1998. However, some non-compliance remains. There is a need for ongoing local audit and formal training in urinary catheter care, particularly for non-qualified care staff. Education is needed to ensure local implementation of NICE guidance.

'Losing my touch': decline in self-reported confidence in performing practical procedures in consultant oncologists.

This study aimed to compare the confidence of oncology consultants and specialist registrars (SpRs) in the performance of practical procedures, to contrast this with confidence in other areas of practice and to determine at what grade they felt most confident. Questionnaires were sent to all 57 oncology consultants and SpRs in the South-West region. Respondents scored confidence on a five-point Likert scale. The response rate was 70%. SpRs were significantly more confident in cardiopulmonary resuscitation (p = 0.003) and central line insertion (p = 0.006). Consultants were significantly more confident in developing management plans (p = 0.001) and performing committee work (p = 0.002). Only 6% of consultants felt most confident performing practical procedures as a consultant, and were less confident about these than other tasks (p = 0.001). Some 86% of SpRs considered they were more confident performing practical procedures as senior house officers (SHOs). In conclusion, self-reported confidence in performing practical procedures declines during career progression in oncology. This raises questions about the teaching and supervision of these procedures. If there is a greater emphasis on a consultant-provided service, their educational needs will need to be recognized and retraining or outsourcing of these procedures to other specialties may be necessary.

Lessons learned from a randomised controlled study of perioperative beta blockade in high risk patients undergoing emergency surgery.

BACKGROUND: Perioperative beta blockade has been shown to reduce mortality after major elective surgery. The aim of this study was to determine whether it could reduce the rate of death and morbidity from cardiac complications in high risk patients undergoing emergency surgery. METHODS: Over a one-year interval all patients undergoing major non-elective orthopaedic or general surgery were screened to identify those at high risk of cardiac complications. Consenting, high risk patients were randomly allocated atenolol or placebo for seven days, commencing at anaesthetic induction. Deaths and cardiac complications within 30 days were recorded. RESULTS: Some 2351 patients had an emergency operation; 145 were at high risk and eligible for the study. Of 89 patients approached, 57 initially consented. Only 38 patients, however, completed the study protocol, 19 were withdrawn. Of those who completed the study, 5/20 patients in the placebo group and 3/18 in the treatment group died before hospital discharge (p=0.520). Four others in the placebo group and two in the atenolol group had post-operative non-fatal cardiac events (positive troponin T), p=0.311. CONCLUSIONS: This study of emergency surgery proved more difficult than similar trials in elective surgery. The final study groups were small and there were no significant differences in outcomes. A much larger study is required for a definitive answer.

An evaluation of the change in activity and workload arising from diabetic ophthalmology referrals following the introduction of a community based digital retinal photographic screening programme.

AIMS: To determine how the workload of an ophthalmology department changed following the introduction of an organised retinal screening programme. METHODS: Information was collected from the hospital medical record of people with diabetes attending eye clinics over 4 years. The first year was before screening, the next 2 years the first round, and the fourth year the second round. RESULTS: The total number of people with diabetes referred each year over the 4 year period was 853, 954, 974, 1051 consecutively. The number of people with diabetes in the county rose by 1400 per annum. The total number of referrals for an opinion about diabetic retinopathy was 227, 333, 363, 368, for cataract was 64, 57, 77, 93, and for glaucoma was 57, 62, 61, 68. The total number of patients referred for laser treatment over the 4 years was 77, 124, 111, and 63 CONCLUSION: This study suggests that the workload in the eye clinic increases in the first round of screening but in subsequent rounds it does not fall below the pre-screening level, except for laser treatment. This may be partly because of increasing numbers of people with diabetes. With the introduction of a national screening programme, this has significant workload implications for the National Health Service.

Angiotensin converting enzyme and angiotensin II type 1-receptor gene polymorphisms and risk of ischaemic heart disease.

OBJECTIVE: Polymorphisms in several genes of the renin-angiotensin system have been implicated as risk factors for myocardial infarction and ischaemic heart disease. In particular, it has been suggested that the angiotensin converting enzyme insertion/deletion (I/D) polymorphism and the angiotensin II type 1 receptor A1166C polymorphisms might act synergistically to increase the risk of myocardial infarction. The aim of this study was to investigate associations between the angiotensin converting enzyme I/D polymorphism and angiotensin II type 1 receptor polymorphisms and ischaemic heart disease. METHODS: We screened 331 white European patients who were recruited for routine angiographic investigation of chest pain, and 287 healthy white European controls for the angiotensin converting enzyme I/D and angiotensin II type 1 receptor A1166C polymorphisms, and related the genotype frequencies to angiotensin converting enzyme levels and the clinical phenotypes of atheroma and history of myocardial infarction. RESULTS: Angiotensin converting enzyme levels were related to I/D polymorphism but not to angiotensin II type 1 receptor polymorphism genotypes. I/D polymorphism and angiotensin II type 1 receptor genotypes did not relate individually to risk of myocardial infarction or atheroma in univariate or multivariate analysis. However, evidence of a synergistic relationship between the AC/II and CC/DD genotypes and coronary stenosis in the major arteries was found. No evidence of any relationship between these polymorphisms and history of myocardial infarction by World Health organisation (WHO) criteria was detected. CONCLUSION: These findings suggest that there is a weak relationship between the angiotensin converting enzyme I/D and angiotensin II type 1 receptor A1166C polymorphisms and coronary atheroma, but no evidence of a relationship with history of myocardial infarction.

Expression of a defense-related 3-hydroxy-3-methylglutaryl CoA reductase gene in response to parasitization by Orobanche spp.

Orobanche spp. are angiosperms that live parasitically on the roots of other plants, and are capable of significantly reducing the yield and quality of their crop hosts. We have demonstrated that parasitization by Orobanche induces expression of hmg2, a defense-related isogene of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) in tobacco. Transgenic tobacco plants expressing a construct containing 2.3 kb of the tomato hmg2 gene promoter fused to the beta-glucuronidase (GUS) reporter gene were parasitized by O. aegyptiaca. Expression of the hmg2:GUS construct was detected within 1 day following penetration of the host root by the O. aegyptiaca radicle and was localized to the region immediately around the site of parasite invasion. This expression continued and intensified over the course of O. aegyptiaca development. In addition, the hmg2:GUS expression was induced by secondary parasitization, where secondary roots of O. aegyptiaca contacted the host root at a distance from the primary attachment site. This GUS expression was specific to plants containing the hmg2:GUS construct, and was not observed in control plants transformed with a construct of the cauliflower mosaic virus 35S promoter fused to the GUS gene. These results indicate that Orobanche parasitization initiates rapid and sustained induction of a defense-related gene in the host root.

Wide variation in lymphocyte steroid sensitivity among healthy human volunteers.

Steroids are frequently used to treat inflammatory conditions in which lymphocytes play a role. We have recently shown that in severe ulcerative colitis, treatment outcome correlates better with in vitro estimates of lymphocyte steroid sensitivity (LSS) than with disease severity. This lead us to examine the range and variability of LSS in the healthy population. Dexamethasone inhibition of lymphocyte proliferation was measured on 54 occasions in 18 volunteers (mean age, 46 yr; range, 23-60 yr) over an 8-month period. Inter- and intra-assay variation in LSS was low when expressed as maximum inhibition achieved, Imax (2.9% and 3.4%, respectively), allowing us to demonstrate a very wide variation in Imax between healthy individuals (-6.7% to 99.7%). In contrast, within-individual variation of Imax was significantly less than between-individual variation (F test, P < 0.0001), consistent with stability of this parameter over time. No correlation was seen between LSS and glucocorticoid receptor density or affinity, suggesting a postreceptor mechanism. Serum cortisol at the time of sampling and skin sensitivity to glucocorticoids also failed to correlate with LSS. This study suggests Imax is a sufficiently stable parameter to categorize healthy individuals according to LSS. The wide range of LSS demonstrated is striking and suggests that up to 30% of the healthy population would fail to respond to steroid therapy for severe inflammatory conditions.

Human alpha-adducin gene, blood pressure, and sodium metabolism.

The adducin genes contribute significantly to population variation in rat blood pressure and cell membrane sodium transport. The 460Trp mutation of the human alpha-adducin gene has been associated with hypertension, in particular hypertension sensitive to sodium restriction. We studied the relationship between the 460Trp mutation and population variation in blood pressure and sodium metabolism. From 603 Scottish families, we selected 151 offspring and 224 parents with blood pressures in either the upper (high) or bottom (low) 30% of the population distribution and measured the 460Trp mutation using allele-specific hybridization. In offspring, we also measured exchangeable sodium, plasma volume, and total body water. Plasma levels of components of the renin-angiotensin system, atrial natriuretic peptide, and cellular sodium and transmembrane sodium efflux were also estimated. The overall frequency of the 460Trp mutation was 27.1%. In offspring and parent groups, we found no difference in the genotype or allele frequencies of the 460Trp mutation between subjects with high or low blood pressure. There was no overall association between the alpha-adducin genotypes and blood pressure variation. In offspring, the 460Trp mutation was not associated with any significant differences in body fluid volumes or exchangeable sodium; levels of plasma renin, angiotensin II, aldosterone, or atrial natriuretic peptide; intracellular sodium; or ouabain-sensitive transmembrane sodium efflux. These findings suggest that in our Scottish population, the alpha-adducin 460Trp polymorphism is not related to blood pressure and does not affect whole body or cellular sodium metabolism.

Glomerular hyperfiltration, high renin, and low- extracellular volume in high blood pressure.

Abnormal renovascular resistance and glomerular filtration rate are characteristic of established hypertension and may also be involved in its pathogenesis. To determine renal and body fluid correlates of the predisposition to high blood pressure, we examined 100 healthy young adults with high or low blood pressure. Within each group, half had parents with high blood pressures, and half had parents with low blood pressures. Renal function and hemodynamics, body fluid volumes, and relevant hormones and genotypes were measured. Subjects with high personal and parental blood pressures had the highest levels of glomerular filtration rate (P<0.02) and plasma active renin concentration and low levels of exchangeable sodium and plasma volume (P<0.02). High glomerular filtration rate was not associated with differences in urinary kallikrein or prostaglandins. Polymorphisms of the renin, angiotensin-converting enzyme, and angiotensinogen genes were not associated with differences in glomerular filtration rate or renin. Subjects with high personal, but low parental, blood pressures had low exchangeable sodium and plasma volumes (P<0.02) but normal glomerular filtration rates. In this population, extracellular volume depletion and high renin are correlates of high blood pressure in early adulthood, and glomerular hyperfiltration is a feature of those who also have familial predisposition to high blood pressure.

The angiotensin I converting enzyme gene and predisposition to high blood pressure.

Phenotypic abnormalities of the renin-angiotensin system have been associated with the predisposition to high blood pressure. The angiotensin I converting enzyme (ACE) gene has been implicated as a candidate gene. We examined the distribution of common alleles of the ACE gene and measured circulating components of the renin-angiotensin system and urinary sodium excretion in 170 young Caucasian adults with contrasting genetic predisposition to high blood pressure. Predisposition was defined on the basis of personal and parental blood pressure levels by using the four corners sampling method. Young adults with greatest predisposition who had high blood pressure and two parents with high blood pressure did not show any significant difference in the distribution of the markers of the ACE gene, either as genotype or allele frequencies, when compared with young adults with least predisposition who had low blood pressure and two parents with low blood pressure. Offspring with urinary sodium excretion above the median (143.4 mmol per day) also showed no significant differences in the distribution of ACE alleles or genotype between groups. Different genotypes were associated with different average serum ACE concentrations (p < 0.0001), but plasma angiotensin II and aldosterone showed no significant variation with ACE genotype. These results suggest that in a group of Caucasians selected from the general population, the ACE gene is not associated with genetic predisposition to high blood pressure. In this population common ACE gene allelic markers would not be useful indexes of susceptibility to hypertension.