Una Martin

Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: Systematic review

Objective To determine the relative accuracy of clinic measurements and home blood pressure monitoring compared with ambulatory blood pressure monitoring as a reference standard for the diagnosis of hypertension. Design Systematic review with meta-analysis with hierarchical summary receiver operating characteristic models. Methodological quality was appraised, including evidence of validation of blood pressure measurement equipment. Data sources Medline (from 1966), Embase (from 1980), Cochrane Database of Systematic Reviews, DARE, Medion, ARIF, and TRIP up to May 2010. Eligibility criteria for selecting studies Eligible studies examined diagnosis of hypertension in adults of all ages using home and/or clinic blood pressure measurement compared with those made using ambulatory monitoring that clearly defined thresholds to diagnose hypertension. Results The 20 eligible studies used various thresholds for the diagnosis of hypertension, and only seven studies (clinic) and three studies (home) could be directly compared with ambulatory monitoring. Compared with ambulatory monitoring thresholds of 135/85 mm Hg, clinic measurements over 140/90 mm Hg had mean sensitivity and specificity of 74.6% (95% confidence interval 60.7% to 84.8%) and 74.6% (47.9% to 90.4%), respectively, whereas home measurements over 135/85 mm Hg had mean sensitivity and specificity of 85.7% (78.0% to 91.0%) and 62.4% (48.0% to 75.0%). Conclusions Neither clinic nor home measurement had sufficient sensitivity or specificity to be recommended as a single diagnostic test. If ambulatory monitoring is taken as the reference standard, then treatment decisions based on clinic or home blood pressure alone might result in substantial overdiagnosis. Ambulatory monitoring before the start of lifelong drug treatment might lead to more appropriate targeting of treatment, particularly around the diagnostic threshold.

Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: A modelling study

BACKGROUND The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension. We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension. METHODS We did a Markov model-based probabilistic cost-effectiveness analysis. We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population. We compared three diagnostic strategies-further blood pressure measurement in the clinic, at home, and with an ambulatory monitor-in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness. FINDINGS Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages. It was cost-saving for all groups (from -£56 [95% CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to 0·022 [0·012 to 0·035] for men aged 70 years). This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive. INTERPRETATION Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment. Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs. FUNDING National Institute for Health Research and the National Institute for Health and Clinical Excellence.

Oxidative stress and normal pregnancy

objective To determine whether, in normal pregnancies, there is evidence of oxidative stress that is related to the lipid changes observed in pregnancy.

Increased levels of exhaled nitric oxide during nasal and oral breathing in subjects with seasonal rhinitis

BACKGROUND Allergic rhinitis is associated with nasal mucosal inflammation. Exhaled nitric oxide may be a useful marker of inflammation and has recently been shown to be increased in patients with asthma. OBJECTIVE The purpose of this study was to determine whether exhaled levels of nitric oxide are increased with nasal breathing in patients with seasonal allergic rhinitis compared with nonatopic individuals and whether there is an increase with oral breathing consistent with lower respiratory inflammation in the absence of clinical asthma. METHODS Nitric oxide levels in exhaled air were measured by chemiluminescence in 18 nonatopic volunteers and 32 patients with seasonal rhinitis. Measurements were made with both nasal and oral exhalation and orally after 10 seconds and 60 seconds of breath-holding. The detection limit was 1 part per billion (ppb). RESULTS In control subjects nasal levels of nitric oxide in exhaled air (mean +/- SD, 24.7 +/- 9.2 ppb) were higher than those after oral exhalation (11.1 +/- 2.5 ppb, p less than 0.0001). Breath-holding significantly increased levels of nitric oxide in exhaled air in a time-dependent manner. Levels of exhaled nitric oxide were significantly higher for all measurements in patients with seasonal rhinitis, with levels without breath-holding of 35.4 +/- 11.3 ppb (p less than 0.001) in nasally exhaled air and 16.3 +/- 5.9 ppb (p less than 0.001) in orally exhaled air. Nasal levels were significantly higher than oral levels in subjects with rhinitis (p less than 0.0001). CONCLUSIONS The results indicate that exhaled nitric oxide may be a useful marker for nasal inflammation in patients with seasonal rhinitis and suggest that generalized airway inflammation may be present, even without clinical asthma, in such patients.

Changes in plasma lipids and markers of oxidative stress in normal pregnancy and pregnancies complicated by diabetes

The purpose of the present study was to determine changes in plasma lipids and markers of oxidative stress longitudinally in pregnancy complicated by diabetes compared with non-diabetic pregnancy. This was carried out by following a group of normal pregnant women (n=17) and groups of pregnant women with Type I diabetes (n=19), Type II diabetes (n=12) and gestational diabetes mellitus (n=12) throughout pregnancy, with sampling carried out at the end of each trimester. Serum total cholesterol and triacylglycerols (triglycerides) were determined using standard colorimetric techniques and low-density lipoprotein (LDL) subfraction profile by disc PAGE. Total antioxidant capacity (TAC) was determined by enhanced chemiluminescence and lipid hydroperoxides by the ferrous oxidation of Xylenol Orange method. Total cholesterol and triacylglycerols increased significantly throughout pregnancy in all groups, but there were no significant differences between normal and diabetic women with respect to either. The LDL score was significantly higher (P<0.001) in diabetic women compared with normal women at each point throughout pregnancy, although there were no significant differences between the diabetic groups. There was evidence of greater oxidative stress in diabetic compared with normal women throughout. Corrected TAC was significantly lower (P<0.001) in all diabetic women throughout pregnancy. In addition, lipid hydroperoxides were higher in all diabetic compared with normal women, particularly so in those with Type II diabetes (P<0.05). These changes may have important implications for diabetic women during pregnancy, as an elevated risk of pre-eclampsia is thought to reflect an oxidative stress-related mechanism. In addition, these changes may have important implications for the development of atherosclerosis and the long-term cardiovascular health of women with diabetes.

LIPID-LOWERING DRUGS AND HOMOCYSTEINE

0·0–3·3). The only cancer was a testis cancer. In daughters the overall cancer risk was high (5 observed; 1·2 expected [RR 4·2; 95% CI 1·4–9·9]). The cancers were one melanoma and one non-melanoma skin cancer and 3 breast cancers at ages 27, 34, and 36 years. Breast cancer occurred in excess of the expected, RR 16·4 (CI 95% 3·3–47·7). None of the cases had mothers with breast cancer, contrary to a previous report from Finland. Excess breast-cancer risk in daughters of male breast-cancer patients corroborates our hypothesis and is in line with previous studies of breast-cancer susceptibility genes. The mean age of our cohort was 32 years, and all breast cancer patients were below 40 years of age, which is in line with findings in Iceland, where 12 out of 49 breast cancers occurred before age 40 years. This high risk may justify screening for BRCA mutations in the offspring of male breast-cancer patients and other measures for early diagnosis of breast cancer.

Glutathione: in sickness and in health

There is increasing evidence that free radical damage may be an important cause of some of the adverse effects of disease and advancing age. Much of the clinical evidence to support this hypothesis is based on the protective effect sometimes observed in those on diets high in antioxidants and those given antioxidants therapeutically. Further support would be obtained if plasma markers for oxidative damage such as lipid peroxidation products (lipid hydroperoxide [LHP]) were raised and antioxidants such as glutathione were low in the old and the sick, particularly in those who are acutely and severely ill. We have therefore measured plasma glutathione and LHP in healthy young individuals, healthy older individuals, and two groups of elderly patients, one with chronic ill-health attending outpatients and one acutely ill and in hospital. We studied 66 young healthy volunteers (mean 24· 5 [SD 4· 7] years) and 58 community-based healthy elderly individuals (70· 7 [4· 8] years). Health was defined as an absence of major medical or surgical illness in the previous 5 years, no hospital admissions, no current medication, and a subjective perception of good health. We also studied 49 patients attending general medical clinics (75· 7 [8· 3] years) with a variety of chronic illnesses including ischaemic heart disease, arthritis, diabetes, and hypertension. Finally, 47 hospitalised elderly patients (77· 2 [8· 6] years) were studied during the course of an acute illness within the first week of admission. Non-fasting venous blood was sampled into standard edetic acid (glutathione) and lithium heparin (LHP) tubes. Samples were all taken by one person (SN) and care was taken to minimise haemolysis. They were centrifuged immediately at 3500 rpm, 4oC for 15 min, and plasma stored at -80oC until analysis. Plasma for glutathione was pre-treated with 30% perchloric acid to stabilise thiol groups. Total plasma glutathione was determined by enzyme-rate assay and plasma LHP by ferrous oxidation of xylenol orange. A sample size of at least 47 in each group was needed to detect a 20% change in plasma glutathione with 80% power at the 95% confidence limit. Statistical difference between groups was determined by ANOVA and the level of significance taken as p<0· 05. The results are presented in the figure. The plasma glutathione in young healthy adults was 0· 54 (SE 0· 02) μmol/L. In the healthy elderly glutathione was significantly lower (0· 29 [0· 01] μmol/L, p<0· 0001). The age-adjusted values for elderly outpatients were significantly lower than in the healthy elderly (0· 24 [0· 01] μmol/L, p<0· 0001) and values for elderly inpatients were lower than for elderly outpatients (0· 17 [0· 01] μmol/L, p<0· 01). The marker for oxidative damage, LHP, was low in the healthy young adults (2· 14 [0· 17] μmol/L) and higher in the healthy elderly (3· 14 [0· 20] μmol/L, p<0· 01). It was higher in the sick elderly (8· 51 [0· 66] and 8· 84 [0· 63] μmol/L in outpatients and inpatients, respectively [p<0· 0001 compared with healthy elderly]).

The human nociceptive flexion reflex threshold is higher during systole than diastole.

A baroreflex mechanism may explain hypertensive hypoalgesia. At rest, arterial baroreceptors are stimulated during the systolic upstroke of the pressure pulse wave. This study examined the effects of naturally occurring variations in baroreceptor activity during the cardiac cycle on an objective measure of pain, the nociceptive flexion reflex (NFR). Two interleaved up-down staircase procedures determined separate NFR thresholds during systole and diastole in 36 healthy, normotensive young adults. On odd-numbered trials, the sural nerve was stimulated electrocutaneously at R + 300 ms whereas on even-numbered trials, stimulation was delivered at R + 600 ms. The NFR threshold was higher at R + 300 ms than R + 600 ms. In contrast, stimulus intensity ratings did not differ between R + 300 ms and R + 600 ms. Stimulation of baroreceptors by natural increases in blood pressure during the systolic phase of the cardiac cycle was associated with dampened nociception.

Effects of artificial and natural baroreceptor stimulation on nociceptive responding and pain

The arterial baroreflex may mediate hypertensive hypoalgesia. Carotid baroreceptors can be artificially stimulated by neck suction and inhibited by compression. Effects of brief neck suction and compression on nociceptive responding and pain were studied in 25 normotensive adults. The sural nerve was electrocutaneously stimulated at threshold intensity during systole or diastole combined with neck suction, neck compression, or no pressure. Nociceptive responding was indexed by electromyographic activity elicited in the biceps femoris. Participants rated the intensity of sural stimulation. Although artificial baroreceptor stimulation (suction) did not affect nociceptive responding, baroreceptor inhibition (compression) reduced pain ratings. In contrast, natural baroreceptor stimulation during systole reduced nociceptive responding compared to diastole, but did not affect pain ratings. The data provide partial support for baroreflex modulation of pain.

Impaired endothelial function in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) patients suffer from excess cardiac deaths due to accelerated atherosclerosis. Endothelial dysfunction is a marker of early atherosclerosis. We tested the hypothesis that SLE patients have impaired endothelial function and assessed the relationship between endothelial function and clinical outcome over the subsequent five years. Thirty-six female SLE patients were compared with 22 healthy age and sex matched controls. Endothelial dependent vasodilatation (EDD) was assessed at the brachial artery in response to shear stress. Endotheliumindependent dilatation induced by glyceryl trinitrate was also measured. Patients were followed for up to five years and the development of damage in the cardiovascular and other systems recorded. SLE patients showed significantly impaired endothelial function (median EDD 5.6%, IQR 3.1–7.2%) compared with healthy controls (median EDD 8.0%, IQR 6.3–9.3%; P = 0.001). Endothelium independent dilatation did not differ between the two groups. Endothelial function was significantly worse in postmenopausal compared with premenopausal women (median EDD 6.6%, IQR 3.9–7.8% versus 3.1%, IQR 2.6–5.1%; P = 0.016). Total cholesterol was inversely correlated with endothelial function in SLE patients (Spearman correlation r = -0.422, P = 0.025). There was no relationship between endothelial function and the development of damage in any organ system, including the cardiovascular system during patient follow-up. Patients with SLE have impaired endothelial function. In the small number of patients studied impaired endothelial function was not associated with a worse cardiovascular outcome over five years.