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N Chapman

Publications and source records attributed to N Chapman.

At least 19 recordsLinked to original sources

New evidence in hypertension and hyperlipidaemia.

The benefits of blood pressure lowering on the risk of cardiovascular disease are seen with all commonly used classes of antihypertensive drugs. Although different drug classes may have different effects on cause specific outcomes (such as myocardial infarction or stroke), no differences are observed between their overall effects on combined major cardiovascular end points. The choice of first line antihypertensive drug is therefore likely to be of less importance than the use of any effective drug, particularly since the majority of patients will need two or more agents to achieve blood pressure goals. Recent trials have provided good evidence that lowering cholesterol with statins reduces the risk of cardiovascular events in "high risk" patients, irrespective of initial cholesterol concentrations. The benefits of both blood pressure lowering and lipid lowering treatment appear to be proportional to the extent of the reduction of blood pressure and lipids achieved.

Angiotensin Receptor Antagonists↗

Effects of a perindopril-based blood pressure-lowering regimen on the risk of recurrent stroke according to stroke subtype and medical history: the PROGRESS Trial.

BACKGROUND AND PURPOSE: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) showed that blood pressure lowering reduced stroke risk in patients with a history of cerebrovascular events. Here, we report the consistency of treatment effects across different stroke subtypes and among major clinical subgroups. METHODS: PROGRESS was a randomized, double-blind trial among 6105 people with a prior history of cerebrovascular events. Participants were assigned to active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). RESULTS: During a mean of 3.9 years of follow-up, active treatment reduced the absolute rates of ischemic stroke from 10% to 8% (relative risk reduction [RRR], 24%; 95% confidence interval [CI], 10 to 35) and the absolute rates of intracerebral hemorrhage from 2% to 1% (RRR, 50%; 95% CI, 26 to 67). The relative risk of any stroke during follow-up was reduced by 26% (95% CI, 12 to 38) among patients whose baseline cerebrovascular event was an ischemic stroke and by 49% (95% CI, 18 to 68) among those whose baseline event was an intracerebral hemorrhage. There was no evidence that treatment effects were modified by other drug therapies (antiplatelet or other antihypertensive agents), residual neurological signs, atrial fibrillation, or the time since the last cerebrovascular event. CONCLUSIONS: Beneficial effects of a perindopril-based treatment regimen were observed for all stroke types and all major clinical subgroups studied. These data suggest that effective blood pressure-lowering therapy should be routinely considered for all patients with a history of cerebrovascular events.

Aged↗

Effects of a perindopril-based blood pressure-lowering regimen on disability and dependency in 6105 patients with cerebrovascular disease: a randomized controlled trial.

BACKGROUND AND PURPOSE: We sought to quantify the effects of blood pressure lowering on long-term disability and dependency among patients with cerebrovascular disease. METHODS: We performed a randomized, double-blind, placebo-controlled trial. A total of 6105 participants with a history of stroke or transient ischemic attack in the past 5 years were recruited from 172 hospital outpatient clinics in 10 countries. Subjects were randomly assigned to the following groups: active treatment (angiotensin-converting enzyme inhibitor perindopril [4 mg/d] for all patients, with the diuretic indapamide added at the discretion of treating physicians) or matching placebo(s). Measurements were disability (defined as a Barthel Index score < or =99/100) and dependency (a positive response to the following question: "In the last 2 weeks has the patient required regular help with everyday activities?"). RESULTS: The median duration of follow-up was 4 years. At the last available assessment, 19% of the active treatment group and 22% of the placebo group were disabled (adjusted odds ratio, 0.76; 95% CI, 0.65 to 0.89; P<0.001). Twelve percent of the active treatment group and 14% of the placebo group were dependent (adjusted odds ratio, 0.84; 95% CI, 0.71 to 0.99; P=0.04). The effects of treatment appeared to be mediated primarily through the prevention of disability and dependency associated with recurrent stroke. Four-year treatment with the study drug regimen would be expected to result in the avoidance of 1 case of long-term disability for every 30 (95% CI, 19 to 79) patients. CONCLUSIONS: Among individuals with cerebrovascular disease, a perindopril-based blood pressure-lowering regimen not only reduced the risk of stroke and major vascular events but also substantially reduced the risks of associated long-term disability and dependency.

Activities of Daily Living↗

Peripheral vascular disease is associated with abnormal arteriolar diameter relationships at bifurcations in the human retina.

Arterial diameters at branch points are believed to conform to design principles that optimize circulatory efficiency and maintain constant shear stress across arterial networks. The objective of this study was to examine whether optimality at bifurcations is affected in individuals with atherosclerosis. Retinal images were analysed in normotensive men with abnormal ankle brachial index (n=13) and healthy controls (n=8), matched for age and clinic blood pressure. Compared with controls, men with peripheral vascular disease had adverse metabolic profiles (relative insulin resistance and greater total cholesterol levels). In healthy men, retinal arterial diameters at bifurcations conformed to predicted optimal values but in men with peripheral vascular disease, junction exponents deviated significantly from the optimum. Retinal arteriolar bifurcation angles did not differ significantly between the groups. Atherosclerosis is associated with abnormalities in the arteriolar network of the retina. In view of the importance of the endothelium in maintaining network co-ordination of branch diameters this is suggestive of a generalized abnormality of endothelial function in atherosclerosis.

Adult↗

Prospectively designed overviews of recent trials comparing antihypertensive regimens based on different drug classes.

Randomized trials have provided clear evidence of the beneficial effects of many different blood pressure-lowering regimens compared with placebo. The comparative effects of antihypertensive regimens based on different drug classes are less well established. The Blood Pressure Lowering Treatment Trialists' Collaboration conducted a series of prospectively designed overviews of randomized trials that compared the effects of different drug classes on major cause-specific outcomes. These overviews found no differences between the effects of regimens based on angiotensin converting enzyme inhibitors and those based on diuretics or b-blockers. There was limited evidence of small differences between regimens based on calcium antagonists and those based on diuretics or beta-blockers. The overviews of regimens based on calcium antagonists compared with those based on angiotensin converting enzyme inhibitors recorded too few events to provide reliable findings. Over the next few years, the findings of ongoing trials and future cycles of overview analyses conducted by the Collaboration should substantially add to these data.

Aged↗

Airborne uranium contamination--as revealed through elemental and isotopic analysis of tree bark.

A new strategy for characterisation of airborne uranium contamination based on ICP mass spectrometric analysis of tree bark is described. The uranium content of tree barks (50 samples) obtained from diverse locations (remote, rural, industrial) varied over almost four orders of magnitude (0.001-8.3 micrograms/g U) with maximum concentrations recorded in the vicinity of a nuclear fuel fabrication plant (0.70-8.3 micrograms/g U). Elevated concentrations were also observed near a coal-fired power station (0.25-0.38 microgram/g U). Isotopic analysis revealed significant deviation from the natural uranium isotope ratio (235U/238U, 0.00725) at four nuclear installations (235U/238U, 0.0055-0.0097). These findings indicate that tree bark serves as an effective biomonitor for uranium and, with isotopic analysis, discrimination between nuclear and non-nuclear emissions is realised.

Air Pollutants, Radioactive↗

QT intervals and QT dispersion as measures of left ventricular hypertrophy in an unselected hypertensive population.

Electrocardiographic (ECG) QT intervals and dispersion correlate with echocardiographic left ventricular mass index (LVMI) in groups of selected essential hypertensives. We tested the strength of this relationship in a large group of unselected hypertensives to assess whether QT measurements may be a simple screening test for LVH in clinical practice. In a cross-sectional study of 386 unselected hypertensive subjects, maximal QT intervals (QTmax), QT dispersion (QTdisp), and ECG voltages (Sokolow-Lyon and Cornell sex-specific voltages) were measured from 12-lead ECG. The LVMI correlated most strongly with Cornell voltage (linear regression r = 0.44, P < .001). The strongest relationship between LVMI and QT parameters was with QTmax, (r = 0.25, P < .001). This relationship weakened using heart rate-corrected QTmax. Correlations between LVMI and QTdisp were weak, whether or not they were corrected for heart rate. Sokolow-Lyon voltages, Cornell voltage and QTmax, but not QTdisp, were independently predictive of LVMI after adjustment for age, sex, race, and the other ECG parameters. Receiver operating characteristic (ROC) curve analyses demonstrated that no QT parameter performed better than simple ECG voltage criteria in the detection of LVH. In conclusion, QTmax, the QT parameter most strongly associated with LVMI, was independently associated with LVMI after adjustment for standard ECG voltage criteria. However, as an isolated measure it was no better than simple ECG voltage criteria as a screening test for LVH in clinical practice.

Adult↗

Blood pressure lowering in diabetes: a brief review of the current evidence and description of a new trial.

1. Diabetes is a major global public health problem. The prevalence of this disease is predicted to increase sharply in the coming decades, particularly in less-developed regions of the world. 2. Most premature morbidity and mortality associated with diabetes relates to markedly increased risks of major cardiovascular diseases, such as myocardial infarction and stroke (macrovascular events), as well as microvascular complications, such as nephropathy and retinopathy. 3. Hypertension is a prevalent and important risk factor for vascular events in these patients. However, observational data demonstrate a continuous relationship between blood pressure and risk of vascular events, suggesting that even those individuals considered normotensive may benefit from blood pressure lowering. 4. Trials of blood pressure lowering among mostly hypertensive individuals with diabetes have demonstrated benefit of intervention on macrovascular and microvascular outcomes. Recent data may suggest additional effects of angiotensin- converting enzyme inhibitors independent of blood pressure lowering. 5. Issues where data are lacking with respect to blood pressure lowering in diabetes include the effects of blood pressure lowering among non-hypertensive individuals and the effects of blood pressure lowering regimens based on different classes of drug. 6. Data expected to address some of these issues are being collected. These include a prospective meta-analysis of blood pressure-lowering trials with large numbers of patients with diabetes. A new large-scale randomised trial, ADVANCE (Action in Diabetes and Vascular Disease), is also described.

Antihypertensive Agents↗

Progress in reducing the burden of stroke.

1. The burden of stroke worldwide is growing rapidly, driven by an ageing population and by the rapid rate of urbanization and industrialization in the developing world. There are approximately 5 million fatal and 15 million non-fatal strokes each year and over 50 million survivors of stroke alive, worldwide, today. 2. The most important determinant of stroke risk is blood pressure, with a strong, continuous relationship between the level of the systolic and diastolic pressures and the risk of initial and recurrent stroke, in both Western and Asian populations. 3. Randomized clinical trials have clearly demonstrated that blood pressure lowering reduces the risk of initial stroke by 35-40% in hypertensive patients; but, until recently, there was no conclusive evidence that blood pressure lowering was effective in the secondary prevention of stroke. 4. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) has provided definitive evidence that blood pressure lowering in patients with previous stroke or transient ischaemic attack (TIA) reduces the incidence of secondary stroke by 28%, of major vascular events by 26% and of major coronary events by 26%. These reductions were all magnified by approximately 50% in a subgroup of patients in whom the angiotensin-converting enzyme inhibitor perindopril was routinely combined with the diuretic indapamide. 5. Successful global implementation of a treatment with perindopril and indapamide in patients with a history of stroke or TIA would markedly reduce the burden of stroke and could avert between 0.5 and one million strokes each year, worldwide.

Angiotensin-Converting Enzyme Inhibitors↗

Challenges for the prevention of primary and secondary stroke: the importance of lowering blood pressure and total cardiovascular risk.

It is well established that blood pressure lowering is effective for the primary prevention of stroke and other cardiovascular disorders in subjects with blood pressures as low as 140/90 mmHg, and up to 80 years of age. Despite this knowledge, blood pressure levels are controlled in less than 25% of the hypertensive population worldwide. It has taken longer to prove that blood pressure lowering is equally effective for the prevention of recurrent stroke. The results of PROGRESS (Perindopril Protection Against Recurrent Stroke Study) have confirmed that a perindopril-based regimen in subjects with cerebrovascular disease substantially reduces the incidence of secondary stroke and primary myocardial infarction. It is daunting to recall that it has taken almost two decades for beta-blockers to be widely used for the secondary prevention of myocardial infarction, since widespread use of the PROGRESS regimen would prevent more than half a million strokes worldwide each year. The real challenge now is to implement novel and effective strategies for the control of blood pressure and other cardiovascular risk factors worldwide. Strategies should include lifestyle measures, such as stopping smoking, exercise and reducing overweight. There is a real need to identify hypertensive subjects and treat them with blood pressure lowering drugs for primary prevention. In subjects with established cardiovascular disease, consideration should be given to a range of proven interventions for secondary prevention, such as blood pressure lowering, irrespective of current blood pressure, anti-platelet drugs, statins for lowering cholesterol and glycaemic control in diabetics. Among new strategies to lower overall cardiovascular risk, consideration should be given to the development of single-pill combinations of drugs of known efficacy, including various combinations of ACE inhibitors, diuretics, beta-blockers, aspirin and statins, among others.

Antihypertensive Agents↗

Computer algorithms for the automated measurement of retinal arteriolar diameters.

AIMS: Quantification of retinal vascular change is difficult and manual measurements of vascular features are slow and subject to observer bias. These problems may be overcome using computer algorithms. Three automated methods and a manual method for measurement of arteriolar diameters from digitised red-free retinal photographs were compared. METHODS: 60 diameters (in pixels) measured by manual identification of vessel edges in red-free retinal images were compared with diameters measured by (1) fitting vessel intensity profiles to a double Gaussian function by non-linear regression, (2) a standard edge detection algorithm (Sobel), and (3) determination of points of maximum intensity variation by a sliding linear regression filter (SLRF). Method agreement was analysed using Bland-Altman plots and the repeatability of each method was assessed. RESULTS: Diameter estimations obtained using the SLRF method were the least scattered although diameters obtained were approximately 3 pixels greater than those measured manually. The SLRF method was the most repeatable and the Gaussian method less so. The Sobel method was the least consistent owing to frequent misinterpretation of the light reflex as the vessel edge. CONCLUSION: Of the three automated methods compared, the SLRF method was the most consistent (defined as the method producing diameter estimations with the least scatter) and the most repeatable in measurements of retinal arteriolar diameter. Application of automated methods of retinal vascular analysis may be useful in the assessment of cardiovascular and other diseases.

Adult↗

Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists' Collaboration.

BACKGROUND: This programme of overviews of randomised trials was established to investigate the effects of angiotensin-converting-enzyme (ACE) inhibitors, calcium antagonists, and other blood-pressure-lowering drugs on mortality and major cardiovascular morbidity in several populations of patients. We did separate overviews of trials comparing active treatment regimens with placebo, trials comparing more intensive and less intensive blood-pressure-lowering strategies, and trials comparing treatment regimens based on different drug classes. METHODS: The hypotheses to be investigated, the trials to be included, and the outcomes to be studied were all selected before the results of any participating trial were known. Individual participant data or group tabular data were provided by each trial and combined by standard statistical techniques. FINDINGS: The overview of placebo-controlled trials of ACE inhibitors (four trials, 12,124 patients mostly with coronary heart disease) revealed reductions in stroke (30% [95% CI 15-43]), coronary heart disease (20% [11-28]), and major cardiovascular events (21% [14-27]). The overview of placebo-controlled trials of calcium antagonists (two trials, 5520 patients mostly with hypertension) showed reductions in stroke (39% [15-56]) and major cardiovascular events (28% [13-41]). In the overview of trials comparing blood-pressure-lowering strategies of different intensity (three trials, 20,408 patients with hypertension), there were reduced risks of stroke (20% [2-35]), coronary heart disease (19% [2-33]), and major cardiovascular events (15% [4-24]) with more intensive therapy. In the overviews comparing different antihypertensive regimens (eight trials, 37,872 patients with hypertension), several differences in cause-specific effects were seen between calcium-antagonist-based therapy and other regimens, but each was of borderline significance. INTERPRETATION: Strong evidence of benefits of ACE inhibitors and calcium antagonists is provided by the overviews of placebo-controlled trials. There is weaker evidence of differences between treatment regimens of differing intensities and of differences between treatment regimens based on different drug classes. Data from continuing trials of blood-pressure-lowering drugs will substantially increase the evidence available about any real differences that might exist between regimens.

Aged↗

Mutations in a conserved enteroviral RNA oligonucleotide sequence affect positive strand viral RNA synthesis.

We showed earlier that a transition mutation U234C, located within the completely conserved 5 nucleotide (nt) tract 5'-CGUUA (nt232-236) in the 5' non-translated region (NTR) of the coxsackievirus B3 (CVB3) genome, attenuated CVB3 cardiovirulence in mice. To further explore the role of the sequence, we induced two single and one double transversion mutations in the conserved 5mer in a cardiovirulent CVB3 genome. The mutated sites partially or totally reverted to parental wild-type when progeny viruses were passaged at 37 degrees C, but remained stable when transfection and subsequent passages were performed at 33.5 degrees C. Viral replication in cell culture was attenuated at 37 degrees C or 39.5 degrees C relative to replication at 33.5 degrees C. While Western blot analysis demonstrated the level of protein translation consistent with virus replication, the ratios of positive to negative strand viral RNA at 37 degrees C in murine cells demonstrated a 2-5 fold diminution from those measured at 33.5 degrees C. Mutant CVB3 strains failed to replicate productively when inoculated into mice. The biological data are consistent with an hypothesis that proposes a lesion with primary effects at the level of positive strand viral RNA synthesis that results in attenuation of viral replication at physiologic temperature.

5' Untranslated Regions↗

Quantification and characterisation of arteries in retinal images.

A computerised system is presented for the automatic quantification of blood vessel topography in retinal images. This system utilises digital image processing techniques to provide more reliable and comprehensive information for the retinal vascular network. It applies strategies and algorithms for measuring vascular trees and includes methods for locating the centre of a bifurcation, detecting vessel branches, estimating vessel diameter, and calculating angular geometry at a bifurcation. The performance of the system is studied by comparison with manual measurements and by comparing measurements between red-free images and fluorescein images. In general an acceptable degree of accuracy and precision was seen for all measurements, although the system had difficulty dealing with very noisy images and small or especially tortuous blood vessels.

Diagnostic Imaging↗

Ethnic and gender differences in electrocardiographic QT length and QT dispersion in hypertensive subjects.

BACKGROUND: Prolonged QT intervals and/or increased QT dispersion (QTd) are associated with various pathological conditions and predict death in healthy individuals. Among hypertensives, QTd correlates with blood pressure (BP) and left ventricular mass index (LVMI) and QT intervals are prolonged in those with left ventricular hypertrophy (LVH). In normotensives, heart-rate corrected QT length (QTc) is longer in females than males, but QTd is greater in males than females. There are few data comparing QT parameters between different ethnic groups and none specifically in hypertensives. Among normotensives, compared with whites, QTc is reported to be shorter in African-Americans and longer in Chinese. We looked for ethnic and gender differences in QT parameters in hypertensive subjects. METHODS: Untreated hypertensives were selected from a Hypertension Clinic database. Black and white subjects were matched for age, sex, BP and LVMI. Male and female subjects were matched for age, race, BP and the presence or absence of echocardiographic LVH. Maximum QT intervals (QTm), rate-corrected maximum QT intervals (QTc) and QT dispersion (QTd) were measured or calculated from ECGs. Data are presented as mean +/- s.d. Differences in QT parameters were sought between groups using Student's t-tests. RESULTS: No ethnic or gender differences in QT parameters achieved statistical significance. However there was a tendency for QTm and QTc to be prolonged in blacks compared with whites (443 +/- 52 vs 421 +/- 47; P = 0.08 and 480 +/- 65 vs 463 +/- 40: P = 0.24 respectively), and for QTc to be prolonged in females compared with males (479 +/- 52 vs 461 +/- 45 ms; P= 0.13). CONCLUSION: In small groups of matched hypertensives, no ethnic or gender differences in QT parameters achieved statistical significance. However, similar to findings in normotensives, QTc tended to be longer in hypertensive females than males. In hypertensives, we failed to confirm the finding that QTc is shorter in blacks than whites, as seen in US normotensives. Whether this represents a difference between hypertensives and normotensives, or between US and UK blacks requires further investigation. Whether the prognostic significance of QT parameters in hypertensives differs between different gender and ethnic groups needs to be established from prospective studies. Journal of Human Hypertension (2000) 14, 403-405

Adult↗

Expression of an antigenic adenovirus epitope in a group B coxsackievirus.

Group B coxsackieviruses (CVB) cause human myocarditis, while human adenovirus type 2 (Ad2) is implicated as an agent of this disease. The L1 loop of the Ad2 hexon protein has been demonstrated to be antigenic in rabbits. To evaluate the feasibility of a multivalent vaccine strain against the CVB and Ad2, we cloned the sequence encoding the Ad2 hexon L1 loop, flanked by dissimilar sequences encoding the protease 2A (2Apro) recognition sites, into the genome of an attenuated strain of CVB type 3 (CVB3/0) at the junction of 2Apro and the capsid protein 1D. Progeny virus (CVB3-PL2-Ad2L1) was obtained following transfection of the construct into HeLa cells. Replication of CVB3-PL2-Ad2L1 in diverse cell cultures demonstrated that the yield of the chimeric virus was between 0.5 to 2 log units less than the parental strain. Western blot analyses of the CVB3 capsid protein 1D in CVB3-PL2-Ad2L1-infected HeLa cells demonstrated production of the expected capsid protein. Viral proteins were detected earlier and in approximately fourfold greater amounts in CVB3-PL2-Ad2L1-infected HeLa cells than in CVB3/0-infected cells. Cleavage of the CVB3-PL2-Ad2L1 polyprotein by 2Apro was slowed, accompanied by an accumulation of the fusion 1D-L1 loop protein. Reverse transcription-PCR sequence analysis of CVB3-PL2-Ad2L1 RNA demonstrated that the Ad2 hexon polypeptide coding sequence was maintained in the chimeric viral genome through at least 10 passages in HeLa cells. Mice inoculated with CVB3-PL2-Ad2L1 demonstrated a brief viremia with no replication detectable in the heart but prolonged replication of virus in the pancreas in the absence of pathologic changes in either organ. CVB3-PL2-Ad2L1 induced binding and neutralizing anti-Ad2 antibodies, in addition to antibodies against CVB3 in mice. CVB3-PL2-Ad2L1 was used to challenge mice previously inoculated with CVB3/0 and with preexisting anti-CVB3 neutralizing-antibody titers; anti-Ad2 neutralizing and binding antibodies were induced in these mice at higher levels than in mice without anti-CVB3 immunity. The data demonstrate that a CVB vector can stably express an antigenic polypeptide of Ad2 from within the CVB open reading frame that results in the induction of protective immune responses against both viruses.

Adenoviruses, Human↗

Improvement in midwall myocardial shortening with regression of left ventricular hypertrophy.

Despite normal indices of left ventricular (LV) chamber function, patients with LV hypertrophy (LVH) due to hypertension are thought to have depressed midwall systolic shortening compared with normotensives. The aims of the present study were (1) to confirm this observation and (2) to assess the effects of antihypertensive therapy that cause regression of LVH on LV systolic function assessed at both the midwall and endocardium. Thirty-eight previously untreated hypertensive subjects with LVH underwent echocardiography and were compared with 38 normotensive control subjects. Comparisons between the group with LVH and the control group revealed no significant differences in cardiac output (4. 32+/-0.23 versus 4.55+/-0.21 L/min), ejection fraction (62.5+/-2% versus 66.4+/-1.07%), or endocardial fractional shortening (34.5+/-1.45% versus 37.0+/-0.82%), but shortening assessed at the midwall was significantly less in the group with LVH (17.9+/-1.11% versus 21.6+/-0.63%, P<0.01). Subsequently, 32 patients with uncontrolled hypertension (24 previously untreated and 8 on existing antihypertensive therapy) underwent treatment with ramipril, with the addition of felodipine and bendrofluazide if required, to reduce blood pressure to <140/90 mm Hg. These 32 patients underwent echocardiography at baseline, after blood pressure control, and after an additional 6 months of tight blood pressure control. Good blood pressure control was achieved after 6 months compared with baseline (143/86+/-2.8/1.4 versus 174/103+/-4.1/1.9 mm Hg; P<0.01) with significant regression of LV mass index (124+/-3.4 versus 145+/-3.8 g/m(2), P<0.01). LV fractional shortening assessed at the midwall improved with regression of LVH (21.9+/-0.84 and 18.7+/-1. 19%, P<0.05), with posttreatment midwall shortening being similar to that of the normal control subjects evaluated in the first study. Hypertensive patients with LVH have depressed midwall systolic shortening despite normal indices of LV chamber function. Regression of LVH after good blood pressure control improved midwall shortening to normal levels.

Adult↗

Acute effects of oxygen and carbon dioxide on retinal vascular network geometry in hypertensive and normotensive subjects.

The optimal design of vascular networks maximizes circulatory efficiency while minimizing power costs. We investigated the effects of acute changes in vascular tone on retinal arteriolar network geometry. Six hypertensive and six normotensive subjects each breathed air, 5% CO(2) (with 12% O(2)), and 100% O(2) for 5 min periods in random order. Retinal photographs were taken at the end of each test period. Bifurcation angles and arteriolar diameters were measured using operator-directed image analysis, and junction exponents were calculated. Arteriolar diameters narrowed on breathing O(2). The magnitude of this change was significantly greater in normotensive than in hypertensive subjects. Angles narrowed in normotensive subjects, but not significantly in hypertensive subjects. Arteriolar diameters increased significantly on breathing CO(2) in normotensive but not in hypertensive subjects, but there were no changes in angles. Despite changes in diameter, junction exponents did not change under any conditions. Vascular reactivity in the retinal arteriolar bed appears to be diminished in hypertensive subjects. The failure of junction exponents to change, despite alterations in diameter, suggests that arteriolar diameters at retinal bifurcations adhere to optimality principles when exposed to acute vasoactive stress. As vasoconstriction is associated with the narrowing of bifurcation angles, previous observations showing narrowed angles in hypertensive subjects could be explained by increased tone in the retinal arteriolar bed.

Adult↗