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Biomedical subjects

G T McInnes

Publications and source records attributed to G T McInnes.

At least 37 records · Page 2Linked to original sources

Integrated approaches to management of hypertension: promoting treatment acceptance.

Overwhelming trial evidence indicates that the treatment of hypertension is beneficial, but in practice, less than 50% of treated hypertensive subjects have blood pressure well controlled. The success of treatment relies on acceptance by the patient. Treatment acceptance may be affected by the efficacy and tolerability of drug therapy, its effects on quality of life, and other important but less well-recognized influences such as the expectations and preconceived ideas of the physician and the patient. This report briefly reviews the factors affecting patient concordance with antihypertensive treatment and the role these factors play in the development of an integrated treatment plan. Nonconcordance with drug therapy is common: Only one third of patients always take treatment, one third take it sometimes, and one third never take their prescribed medication. With poor concordance, control of blood pressure and the consequent benefits are less likely to be realized. The factors that influence concordance are ill understood. Although drug side effects and convenience of dosing regimens are contributors, the attitudes of patients, physicians, and their interactions are likely to be of considerable importance. Concordance may be improved by involving the patient in the treatment plan, setting explicit targets, following a clear treatment plan, motivating the patient to comply with treatment, paying attention to the concerns and particular needs of the individual patient, and by ensuring frequent contacts between patients and health care professions. Successful integrated approaches to the management of hypertension must address all the factors that affect treatment acceptance.

Antihypertensive Agents↗

Compliance with aspirin or placebo in the Hypertension Optimal Treatment (HOT) study.

OBJECTIVE: The Hypertension Optimal Treatment (HOT) study is a large, prospective trial aimed at defining the level of diastolic blood pressure required during anti-hypertensive therapy in order to achieve maximal protection against cardiovascular complications. A further aim is to assess the effects on morbidity and mortality of a 75 mg daily dose of aspirin compared with placebo. SUBJECTS AND METHODS: Compliance with double-blind administration of aspirin or placebo added to anti-hypertensive treatment was evaluated for 1 year in a subset (n = 530) of the study population (n = 18 790) by placing the medication in a container closed with an electronic cap that records precisely the time of each opening. RESULTS: The 1-year compliance rate (percentage of days with one opening per day) could be assessed in 501 patients. It averaged 78.3 +/- 25% in aspirin-treated patients (n = 236, mean +/- SD), compared with 78.5 +/- 25% in patients having received placebo (n = 265), and was not influenced by age, sex or country (Germany, Italy, Switzerland, UK). The compliance rate was also similar irrespective of whether the patients had reached their target blood pressure, but was significantly better during the first than the second 6-month monitoring period (84.1 +/- 22% versus 72.3 +/- 32%, n = 501). CONCLUSIONS: The high rate of compliance with aspirin or placebo observed in the HOT study suggests that the patients were highly motivated and may account for the unusually good blood pressure control achieved in this trial during long-term anti-hypertensive treatment.

Aged↗

Angiotensin II antagonism in clinical practice: experience with valsartan.

Angiotensin (Ang) II antagonists provide specific and selective blockade of Ang II at the AT1 receptor, regardless of the enzymatic pathway of production. Valsartan has an affinity for the AT1 receptor 30,000 times that of the AT2 receptor. Valsartan is not a prodrug and undergoes little metabolism. It has a half-life of approximately 9 h, but duration of antihypertensive action at the usual dose of 80 or 160 mg daily is 24 h. The trough to peak ratio is 0.66. Valsartan has antihypertensive efficacy at least equivalent to that of established antihypertensive drugs and has additive effects in combination. The efficacy of valsartan appears to be independent of age, sex, and race. Valsartan is effective in hypertensive patients with renal insufficiency and is associated with maintenance of renal function. It is well tolerated, with a side-effect profile indistinguishable from that of placebo, and does not cause cough. Ang II antagonists are a promising class of cardiovascular drugs with considerable potential in clinical practice.

Age Factors↗

Clinical advantage of valsartan.

Valsartan is a specific angiotensin II receptor antagonist with high selectivity for the AT(1) receptor subtype. After oral administration of single or repeated once-daily doses, valsartan 40-80 mg inhibits the pressor response to angiotensin II for 24 hours. In patients with mild-to-moderate hypertension, efficacy of valsartan appears to be independent of age, sex, and race, and is at least equivalent to that of calcium antagonists, ACE inhibitors, or thiazide diuretics. Response rate to valsartan 160 mg o.d. is significantly greater than after receiving losartan 100 mg o.d. Valsartan has additive effects with other antihypertensive drugs and combination therapy is effective in severe hypertension and in hypertension with renal insufficiency, where renal function is well maintained. Valsartan has good tolerability with a side-effect profile indistinguishable from placebo and superior to that of comparable drugs. Valsartan does not cause cough or adverse metabolic effects; first dose hypotension and rebound hypertension on abrupt withdrawal have not been encountered. Valsartan has clear clinical advantage in the management of hypertension. Its impact on prognosis in patients with a high risk of cardiovascular morbidity and mortality is under evaluation.

Antihypertensive Agents↗

Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer?

BACKGROUND: Previous studies have reported an increased risk of cancer with calcium-channel blockers in man. Other work in animals suggests that inhibitors of angiotensin-I-converting enzyme (ACE) protect against cancer. We aimed to assess the risk of cancer in hypertensive patients receiving ACE inhibitors or other antihypertensive drugs. METHODS: Our retrospective cohort study was based on the records of 5207 patients who attended the Glasgow Blood Pressure Clinic between Jan 1, 1980, and Dec 31, 1995. The patients' records are linked with the Registrar General Scotland and the West of Scotland Cancer Registry. FINDINGS: Compared with the West of Scotland controls, the relative risks of incident and fatal cancer among the 1559 patients receiving ACE inhibitors were 0.72 (95% CI 0.55-0.92) and 0.65 (0.44-0.93). Among the 3648 patients receiving antihypertensive drugs other than ACE inhibitors (calcium-channel blockers 1416, diuretics 2099, beta-blockers 2681), the corresponding relative risks were 110 (0.97-1.22) and 1.03 (0.87-1.20). The relative risk of cancer was lowest in women on ACE inhibitors: 0.63 (0.41-0.93) for incident cancer; 0.48 (0.23-0.88) for fatal cancer; and 0.37 (0.12-0.87) for female-specific cancers. The reduced relative risk of cancer in patients on ACE inhibitors was greatest with follow-up of longer than 3 years. Calcium-channel blockers, diuretics, and beta-blockers had no apparent effect on risk of cancer. INTERPRETATION: Long-term use of ACE inhibitors may protect against cancer. The status of this finding is more that of hypothesis generation than of hypothesis testing; randomised controlled trials are needed.

Angiotensin-Converting Enzyme Inhibitors↗

Cancer risk of hypertensive patients taking calcium antagonists.

OBJECTIVE: To measure rates of incident and fatal cancer in hypertensive patients taking calcium antagonists and to compare these with rates in three control groups. DESIGN: A retrospective analysis of cancer in patients of the Glasgow Blood Pressure Clinic prescribed either a calcium antagonist or other antihypertensive drugs (non-calcium antagonist group). Record linkage of the clinic with the West of Scotland Cancer Registry and with the Registrar General, Scotland provided information on incidence of cancer and on deaths and their causes. PATIENTS: 2297 patients were prescribed calcium antagonist and 2910 were prescribed antihypertensive drugs other than calcium antagonist. MAIN OUTCOME MEASURES: Relative risk of cancer, the ratio of observed to expected cancers in the calcium antagonist group, was estimated using expected values based on three control groups; namely the non-calcium antagonist group, a middle-aged population of Renfrew and Paisley and the West of Scotland population. RESULTS: There were 134 incident cancers in the calcium antagonist group, representing relative risks of 1.02 [95% confidence interval (CI) 0.82-1.271 compared with the non-calcium antagonist group, 1.01 (95% CI 0.84-1.18) compared with Renfrew-Paisley controls and 1.02 (95% CI 0.85-1.19) compared with West of Scotland controls. Findings for cancer mortality were similarly negative. Risks were no higher for older patients. CONCLUSIONS: Our study lends no support to the suggestion that calcium antagonists cause cancer.

Aged↗

The efficacy and tolerability of candesartan cilexetil in an elderly hypertensive population.

This study was performed to evaluate the antihypertensive efficacy and tolerability of candesartan cilexetil 8-16 mg once-daily in comparison with placebo in elderly hypertensive patients. Forty-one hospital and general practice centres in the Netherlands and in the United Kingdom enrolled 350 patients over 65 years of age with essential hypertension (WHO grades I or II). Patients with supine diastolic BP in the range 95-114 mm Hg after 4- to 8-week placebo run-in period (n = 193) were randomised to double-blind therapy with candesartan cilexetil or placebo. The initial dose of candesartan cilexetil 8 mg or placebo was doubled after 6 weeks if supine diastolic blood pressure (BP) exceeded 90 mm Hg. Mean (95% confidence interval) placebo-corrected reduction in supine diastolic BP after 12 weeks' treatment with candesartan cilexetil was 7.5 mm Hg (3.6-11.4; P < 0.001); the corresponding reduction in supine systolic BP was 13.6 mm Hg (6.9-20.2; P < 0.001). Placebo-corrected mean reduction in supine diastolic BP 2 and 4 h after the first dose of candesartan cilexetil were 2.2 mm Hg (-1.3 to +5.8; P = 0.219) and 4.0 mm Hg (-0.4 to +7.6; P = 0.027), respectively. Candesartan cilexetil had almost no influence on heart rate and did not affect the normal orthostatic changes in BP. Adverse events were equally common in the two treatment groups. Candesartan cilexetil 8-16 mg once-daily is an effective antihypertensive agent in elderly patients. The onset of action is smooth with no exaggerated response after the first dose and there is no postural hypotension. Candesartan cilexetil is very well tolerated in elderly hypertensives.

Aged↗

Investigation of the mechanism of beta 2-agonist-induced activation of the renin-angiotensin system.

1. We have previously described activation of the renin-angiotensin system in asthma, and also by high-dose nebulized beta 2-agonists. In this study we sought to determine the mechanism responsible. 2. The influence of the angiotensin-converting enzyme inhibitor, lisinopril, on the response of the renin-angiotensin system and serum potassium to nebulized salbutamol was investigated in a randomized, double-blind, crossover study in eight healthy volunteers using a factorial block design. On study days, subjects received lisinopril 20 mg orally or identical placebo tablets followed 3 h later by nebulized salbutamol or placebo inhalation; plasma renin, angiotensin II, serum angiotensin-converting enzyme and potassium were measured at intervals for 120 min after inhalation. 3. Following salbutamol, plasma renin and angiotensin II concentrations were increased significantly compared with placebo [mean (SEM) plasma renin of 61.7 (15.6) mu-units/ml and angiotensin II of 17.7 (5.4) pg/mol 15 min after salbutamol, P < 0.05 versus placebo]. Baseline plasma renin concentrations were increased [160.1 (20.6) mu-units/ml] and baseline plasma angiotensin II concentrations were reduced [1.4 (0.1) pg/ml] by lisinopril, P < 0.05 versus placebo in each case. Inhibition of angiotensin-converting enzyme completely inhibited this salbutamol-induced rise in plasma angiotensin II [mean (SEM) plasma angiotensin II of 1.5 (0.4) pg/ml 15 min after salbutamol, P < 0.05 versus placebo] but had no effect on the changes in plasma renin concentrations after the beta 2-agonist [mean (SEM) plasma renin of 198.4 (18.9) mu-units/ml 15 min after salbutamol].(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Hypertension and coronary artery disease: cause and effect.

NATURE OF RELATIONSHIP BETWEEN HYPERTENSION AND CORONARY ARTERY DISEASE: Epidemiological data indicate a strong and consistent link between hypertension and coronary artery disease. This does not mean that hypertension is the cause of coronary artery disease. Less than a quarter of the risk of developing coronary artery disease can be attributed to raised blood pressure. Furthermore, in individuals, hypertension is only weakly predictive and hence blood pressure cannot be relied upon to identify those with a particularly high risk. EFFECT OF A REDUCTION IN BLOOD PRESSURE ON CORONARY ARTERY DISEASE: The results of outcome trials, largely in men with mild to moderate uncomplicated hypertension, demonstrate that a modest short-term reduction in blood pressure confers a reduction in coronary artery disease events of about 16%, against the expectation from observational studies of about 22.5%. Explanations for the apparent shortfall include the putative theory that metabolic effects of the drugs used in the trials (mainly thiazides and beta-blockers) offset the beneficial effect of the blood pressure reduction. However, from consideration of epidemiological findings, it is clear that a large proportion (over 75%) of events in hypertensive patients is unlikely to be preventable by managing the elevated blood pressure alone. TREATMENT CONSIDERATIONS: Since arterial pressure interacts in a more than additive manner with coincident coronary risk factors, treatment should be initiated on the basis of overall risk and directed by predictors of myocardial infarction. In addition to a sustained level of blood pressure, these predictors include established coronary artery disease, older age and cigarette smoking. BEYOND BLOOD PRESSURE REDUCTION: Whether metabolically neutral antihypertensive drugs can reduce the shortfall between expected and observed benefit remains uncertain. However, some newer agents (angiotensin converting enzyme inhibitors and calcium antagonists) appear to have an effect on vascular structure and function that is independent of blood pressure reduction. If these advantages are confirmed in clinical trials, these drugs offer the prospect of a much greater impact on coronary artery disease than currently obtained.

Antihypertensive Agents↗

Delivery of care for hypertension.

To overcome shortcomings in the delivery of care for hypertension various approaches have been developed including a system whereby care of hypertension is shared in a formal manner between general practitioners and hospital specialists. The feasibility, acceptability and cost-effectiveness of a computerised model of shared care were investigated in three matched groups of patients attending hypertension clinics in Glasgow. Glasgow Blood Pressure Clinic attenders considered suitable for shared care by their consultants were randomised to shared care (n = 277) or continued clinic follow-up; a further control group (n = 277) was identified from an independent nurse-practitioner clinic. After 2 years of follow-up, feasibility was estimated by the proportion of patients who had undergone an adequate review (blood pressure, serum creatinine and electrocardiograph); acceptability to general practitioners and patients was assessed by questionnaires; cost-effectiveness was calculated as the cost (to National Health Service and patient) per adequate review. The drop-out rate for shared care over 2 years was 3% compared with 14% for the outpatient clinic and 9% for the nurse-practitioner clinic. In year 2, rates of adequate reviews were 82%, 52% and 75%, respectively. Blood pressure control was similar in the groups. Of 297 general practitioners invited to participate, 85% agreed and 68% wished to continue participation after 2 years. About 50% of shared care patients preferred this method of follow-up compared with their earlier experience of clinic attendance. Shared care was more cost-effective than either conventional or nurse-practitioner clinic follow-up, especially with respect to cost to the patient; costs per adequate review (pound sterling) were 28.96, 50.55 and 30.95, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Delivery of Health Care↗

Comparison of lipid-lowering effects of low-dose fluvastatin and conventional-dose gemfibrozil in patients with primary hypercholesterolemia.

A total of 123 patients with primary hypercholesterolemia were randomized on a 2:1 ratio to receive either fluvastatin at 20 mg once daily at night (n = 82) or gemfibrozil at 600 mg twice daily (n = 41) in a double-blind, double-dummy comparison of the effects on plasma lipid parameters and tolerability over 8 weeks. All patients had either low-density lipoprotein cholesterol (LDL-C) concentrations > or = 160 mg/dL (4.1 mmol/L) in association with definite coronary artery disease (CAD) or > or = 2 risk factors, or LDL-C > or = 190 mg/dL (4.9 mmol/L) with no CAD and < 2 risk factors. All had triglyceride (TG) levels < or = 350 mg/dL (4.0 mmol/L). After 8 weeks of treatment, fluvastatin produced significant reductions from baseline of 17.4% (p < 0.001) in LDL-C, 13.2% (p < 0.001) in total cholesterol (TC), 13.8% (p < 0.001) in very low-density lipoprotein cholesterol (VLDL-C), and 6.4% (NS) in TG. High-density lipoprotein cholesterol (HDL-C) was increased by 5.6% (p < 0.001), and the ratio of LDL-C:HDL-C (Friedewald) was decreased by 21.2% (p < 0.001). Gemfibrozil reduced LDL-C by 15.8%, TC by 13.4%, VLDL-C by 32.2%, LDL-C:HDL-C by 24.8%, and TG by 34.2%, and increased HDL-C by 13.9% (all changes were statistically significant, p < 0.001) compared with baseline. Gemfibrozil produced significantly greater changes in VLDL-C (p < 0.01), HDL-C (p < 0.001), and TG (p < 0.001), but not in LDL-C: HDL-C, compared with fluvastatin. Both drugs significantly reduced apolipoprotein (apo) B and lipoparticles (Lp) E:B, and increased apo A-I but had divergent effects on LpA-I (increased with fluvastatin and reduced with gemfibrozil; p < 0.05). At the end of the study, 43.8% of fluvastatin patients and 45% of gemfibrozil patients achieved a reduction of > 20% in LDL-C levels. Normalization of LDL-C levels was achieved (according to European Atherosclerosis Society guidelines) by 13.4% of fluvastatin- and 14.6% of gemfibrozil-treated patients. Both drugs were well tolerated; adverse events occurred in 36.6% of fluvastatin recipients compared with 58.5% of patients taking gemfibrozil. No clinically notable elevations of aspartate or alanine aminotransferases, alkaline phosphatase, or creatine phosphokinase occurred. No patient developed new or worsening lens opacities associated with a reduction in optically corrected visual acuity. The most commonly reported adverse events were headache and gastrointestinal upset. There were no serious drug-related adverse events.

Adult↗

Hypertension: investigation, assessment and diagnosis.

Patients with mild to moderate hypertension require only a simple schedule of investigations, especially if there is a history of stroke or hypertension in first degree relatives. Tests are necessary to profile other cardiovascular risk factors and to detect target organ damage with only limited screening for secondary hypertension. Careful history, physical examination, repeated blood pressure measurements over months and measurements of body mass index, random cholesterol, routine blood chemistry and urinalysis using impregnated paper strips are all that are required. More detailed investigations can be reserved for special groups such as those with peripheral vascular disease or abnormal renal function before or after treatment with angiotensin converting enzyme inhibitors or significant proteinuria or hypokalaemia. Patients with essential hypertension who are smokers with lipid abnormalities may go on to develop superimposed renovascular disease. Severe hypertension at any age and especially if there is a reliable negative family history also merits special consideration. Resistance to antihypertensive treatment is more often due to non-compliance or non-steroidal anti-inflammatory drug use or alcohol abuse than to underlying secondary causes.

Blood Pressure Determination↗

Coordinating and standardizing long-term care: evaluation of the west of Scotland shared-care scheme for hypertension.

BACKGROUND: The long-term management of patients with chronic conditions such as hypertension presents problems for the health services. Shared care addresses these by coordinating care and defining responsibilities. AIM: This study set out to investigate the feasibility, acceptability and cost effectiveness of shared general practitioner-hospital care for well-controlled hypertensive patients in an urban area by comparing three matched groups of patients. METHOD: A total of 554 outpatient clinic attenders, considered suitable for shared care by their consultant, were randomly allocated to shared care or follow up in the outpatient clinic; a third group of 277 patients was selected from a nurse practitioner clinic. Main outcome measures were the proportion of patients in the second year of follow up who had undergone a complete review (blood pressure measurement, serum creatinine level result and electrocardiograph report), acceptability to patients and general practitioners as assessed by questionnaire, and cost per complete review in year two (National Health Service and patient costs). RESULTS: After two years 220 (82%) shared care patients had had a complete review compared with 146 (54%) outpatient clinic attenders and 202 (75%) nurse practitioner clinic attenders. Blood pressure control was similar in each group. Of 297 general practitioners invited, 85% wished to participate in the study; 61% of questionnaire respondents subsequently wanted shared care to continue while 25% were unsure. Half of the patients receiving shared care preferred this method of follow up. The rank order of cost-effectiveness ratios was shared care, nurse practitioner care and conventional outpatient care, relative differences being most marked when only patient costs were considered. CONCLUSION: Shared care for hypertension is feasible in an urban setting, acceptable to the majority of participants and is a cost-effective method of long-term follow up.

Chronic Disease↗

Mechanical stretch increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells.

OBJECTIVE: To determine whether changes in haemodynamic load, simulated in vitro by mechanically stretching cultured vascular smooth muscle cells, could be transduced into biochemical signals similar to those produced by growth factors. DESIGN: A system was developed which was capable of stretching cultured vascular smooth muscle cells from 0 to 20%. The effect of stretching quiescent vascular smooth muscle cells on both c-fos messenger RNA (mRNA) expression and release of total inositol phosphates was determined over a time interval of 0-360 min. METHODS: Rat mesenteric artery vascular smooth muscle cells were grown using standard cell culture methods. Induction of the proto-oncogene, c-fos, was determined by Northern blotting. Phosphoinositide breakdown was assessed by measuring [3H]-inositol phosphates released from prelabelled cells. RESULTS: A 20% fixed stretch resulted in a rapid induction of c-fos mRNA which reached maximal levels by 15 min. The amount of c-fos mRNA detected was dependent on the degree of stretch, with maximum induction obtained for 15 and 20% stretch. The effects of mechanical stretch were also assessed on phosphoinositide turnover by measuring [3H]-inositol phosphates released from prelabelled cells. A 20% fixed stretch of vascular smooth muscle cells for 20 min resulted in a 3.2-fold increase in total [3H]-inositol phosphates released compared with unstretched cells. CONCLUSIONS: Our results show that mechanical stretch increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells in vitro. These observations suggest that mechanical stretch and growth factors share common signal transduction pathways which may be important in the development of vascular hypertrophy.

Animals↗

Acute effects of cicletanine in angina pectoris.

The anti-anginal properties of single doses of a new anti-hypertensive drug, cicletanine, were investigated in a double-blind, randomised, balanced, crossover comparison with placebo in sixteen patients with chronic stable angina pectoris. All subjects underwent treadmill exercise 2 h after drug administration and 24 h ambulatory ECG monitoring with ST scanning. Although there were significantly fewer episodes of ST depression on ambulatory monitoring after cicletanine, total exercise duration and time to 1 mm ST depression were unchanged. This report provides little evidence of an acute anti-anginal effect of cicletanine but longer term studies may be indicated to further evaluate this drug's potential role in the management of angina pectoris.

Adult↗