Awareness, management and follow-up of lipoprotein disturbances in hypertension.
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Cardiovascular Diseases↗
Biomedical subjects
T Hedner
Publications and source records attributed to T Hedner.
Altered neuropeptide Y Y1 responses in mesenteric arteries in rats with congestive heart failure.
The aim of the present study was to elucidate if the potentiating effect of neuropeptide Y on various vasoactive agents in vitro is (1) altered in mesenteric arteries from rats with congestive heart failure and (2) mediated by the neuropeptide Y Y1 receptor. The direct vascular effects of neuropeptide Y and its modulating effects on the contractions induced by endothelin-1-, noradrenaline-, 5-hydroxytryptamine (5-HT)-, U46619-(9,11-dideoxy-11alpha, 9alpha-epoxymethano-prostaglandin F2alpha) and ATP, and acetylcholine-induced dilatations were studied in the presence and absence of the neuropeptide Y Y1 antagonist, BIBP3226 (BIBP3226¿(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl ]-D-arginine-amide¿). Neuropeptide Y, per se, had no vasoactive effect in the arteries. The potency of endothelin-1 was significantly decreased in congestive heart failure rats. Neuropeptide Y and neuropeptide Y-(13-36) potentiated the endothelin-1-induced contraction in congestive heart failure mesenteric arteries. In 20% of the congestive heart failure rats, sarafotoxin 6c induced a contraction of 31+/-4%. Neuropeptide Y also potentiated U46619- and noradrenaline-induced contractions but not 5-HT-induced contractions in congestive heart failure arteries. In sham-operated animals neuropeptide Y potentiated noradrenaline- and 5-HT-induced contractions. These potentiations were inhibited by BIBP3226. Acetylcholine induced an equipotent relaxation in both groups which was unaffected by neuropeptide Y. In conclusion, neuropeptide Y responses are altered in congestive heart failure rats. The potentiating effect differs between vasoactive substances. Neuropeptide Y Y1 and non-neuropeptide Y1 receptors are involved.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Survival in treated hypertension: follow up study after two decades.
OBJECTIVE: To compare survival and cause specific mortality in hypertensive men with non-hypertensive men derived from the same random population, and to study mortality and morbidity from cardiovascular diseases in the hypertensive men in relation to effects on cardiovascular risk factors during 22-23 years of follow up. DESIGN: Prospective, population based observational study. SUBJECTS AND METHODS: 686 hypertensive men aged 47-55 at screening compared with 6810 non-hypertensive men. The hypertensive men were having stepped care treatment with either beta adrenergic blocking drugs, thiazide diuretics, or combination treatment. Mortality, morbidity, and adverse effects were registered at yearly examinations and from death certificates. MAIN OUTCOME MEASURES: All cause mortality and cause specific mortality. RESULTS: Treated hypertensive men had significantly impaired probability of total survival as well as survival from coronary heart disease and stroke. All cause mortality as well as coronary heart disease and stroke mortality were very similar in hypertensive men and normotensive men during the first decade, but increased steadily thereafter despite continuous good blood pressure control. Smoking, signs of target organ damage, and high serum cholesterol levels, but not blood pressure at screening, were significantly related to the incidence of coronary heart disease during follow up. In time dependent Cox's regression analysis, the incidence of coronary heart disease was significantly related only to serum cholesterol concentrations in the study. Cancer mortality was almost similar in treated hypertensive men (61/686, 8.9%) and non-hypertensive men (732/6810, 10.8%). CONCLUSION: Treated hypertensive men had impaired survival and increased mortality from cardiovascular disease compared with non-hypertensive men of similar age. These differences were observed during the second decade of follow up. During an observation period of 22-23 years-about 15 000 patient years-hypertensive men receiving diuretics and beta blockers had no increased risk of cancer or non-cardiovascular disease.
Adrenergic beta-Antagonists↗
[Is antihypertensive treatment a risk factor of coronary disease? Therapy-related triglyceride increase nor diabetes increase the risk].
In an observational study designed to determine whether metabolic changes during long-term antihypertensive drug treatment are associated with an increased risk of coronary heart disease (CHD), 686 middle-aged hypertensive men recruited from a random population screening sample were followed up for 15 years. Antihypertensive treatment predominantly consisted of beta-adrenoceptor blockers and/or thiazide diuretics. CHD and diabetes mellitus were checked for at annual examinations. Time-dependent Cox regression analysis was used to determine correlation between the incidence of CHD and entry characteristics, the monitored serum levels of cholesterol and triglyceride concentrations and the development of diabetes mellitus. Univariate analysis showed the presence of diabetes mellitus a entry to the study and increased baseline serum concentrations of cholesterol and of triglycerides each to be a significant predictor of CHD, the respective relative risks (RR) being 2.12, 1.21 and 1.21. However, analysis of monitored levels of metabolic variables during follow-up showed only an increased serum cholesterol concentration to be significantly and independently associated with CHD (RR 1.07). Although serum triglyceride concentrations increased slightly during follow-up, they were unrelated to the incidence of CHD; nor was onset of diabetes mellitus during follow-up significantly associated with an increased risk of CHD (RR 1.48. Thus, the study showed the presence of metabolic disturbances such as diabetes mellitus and hyperlipidaemia before the start of antihypertensive treatment to be of positive predictive value in middle-aged hypertensive men, and an increase in the monitored serum cholesterol level to be an independent predictor of CHD, whereas neither drug-related diabetes nor an increase in the monitored serum triglyceride concentration seemed to be associated with the occurrence of CHD.
Adrenergic beta-Antagonists↗
The early clinical history of salicylates in rheumatology and pain.
The first clinical reports on the treatment of fever and pain with salicylate-containing natural willow bark remedies were made by the English clergyman Edward Stone in 1763. The pharmacologically active principles were isolated from natural sources by Italian, German and French scientists between 1826 and 1829. Salicylic acid was first synthesised by the German Gerland in 1852 and a year later the Frenchman Gerhardt synthesised acetylsalicylic acid. The first reports on the clinical use of salicylic acid in rheumatic disorders were made independently by the two German physicians Stricher and Reiss in 1876. Acetylsalicylic acid was rediscovered by Hoffmann in 1897 and by the turn of the century it had gained worldwide recognition in the treatment of pain and rheumatological disorders. Reports on adverse events relating to gastrointestinal intolerance and bleeding appeared early, but were largely neglected until the 1950s. Today, salicylates are still widely used as analgesic, antipyretic and anti-inflammatory drugs. New indications, such as thrombosis prophylaxis, have emerged during the last decades, and yet others are being explored.
Europe↗
Elevation of an endogenous inhibitor of nitric oxide synthesis in experimental congestive heart failure.
OBJECTIVE: NG,NG-dimethylarginine (asymmetric dimethylarginine, ADMA) is an important endogenous substance with potent inhibitory actions on nitric oxide (NO) synthesis. The present study was designed to determine circulating ADMA levels and endothelium-dependent, NO mediated vasodilation in a rat model of congestive heart failure (CHF). METHODS: CHF was induced in rats by coronary artery ligation. Sham-operated rats served as normal controls. Plasma ADMA was determined by high performance liquid chromatography with fluorescence detection. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured by the clearance of inulin and p-aminohippuric acid, respectively. Endothelial function of the aorta was assessed in an organ bath. RESULTS: Plasma levels of ADMA in rats with CHF (0.94 +/- 0.05 mumol/l) were significantly increased compared with sham-operated controls (0.75 +/- 0.06 mumol/l, p < 0.05). Plasma levels of ADMA was negatively correlated with GFR (r = -0.65, p < 0.05). Decreased endothelium-dependent relaxation to acetylcholine in the aorta of CHF was completely restored by L-arginine (300 microM) (p < 0.01) while endothelium-independent relaxation to nitroprusside was not altered. ADMA potently inhibited endothelium-dependent relaxation in thoracic aorta of normal and CHF rats. The effect of ADMA was completely antagonized by L-arginine in both groups (p < 0.01). Moreover, L-arginine improved endothelium-dependent relaxation in CHF rats in the presence of ADMA. CONCLUSIONS: An endogenous NO synthesis inhibitor ADMA is increased in the circulation of rats with CHF. The increased plasma levels of ADMA may contribute to the decreased endothelium-dependent relaxation in CHF, which is restored by L-arginine, possibly by competitive antagonism of ADMA.
Acetylcholine↗
Morphine use and pharmacokinetics in patients with chest pain due to suspected or definite acute myocardial infarction.
The characteristics of chest pain due to suspected acute myocardial infarction and morphine use during the first 3 hospital days are described in a population of 2988 consecutive patients admitted to hospital. The duration of pain was usually less than 24 h (mean 20.9+/-0.55 h), and only 24.8% of patients experienced chest pain of longer duration. The majority of patients had only one attack of pain, but 34.4% experienced four or more attacks during hospitalization. A mean morphine dose of 6.7+/-0.2 mg was administered over the 3 hospitalization days, but surprisingly 52.4% of all patients required no morphine analgesia at all. Independent predictors of an increased morphine consumption were initial degree of suspicion of acute myocardial infarction, ST changes on admission ECG, male sex, a history of angina pectoris and a history of congestive heart failure. In a separate pharmacokinetic/pharmacodynamic study in 10 patients, plasma concentrations of morphine and its major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), were measured after intravenous administration of morphine. In this patient group, terminal half-life of unchanged morphine ranged from 0.77 to 3.22 h. M3G and M6G plasma concentrations increased gradually up to 60-90 min after the intravenous morphine injection. Initial pain intensity by numerical rating scale was 6.6+/-0.6 (arbitrary units), and after morphine administration, there was a rapid and significant decrease in pain intensity. After 20 min, pain relief was 69+/-11% and remained at this level during the following 8 h observation period. It is concluded that the need for morphine administration in patients with suspected or definite acute myocardial infarction, differs among subgroups of patients and, in particular, higher doses are needed in those with a strong suspicion of myocardial infarction at arrival. When intravenous morphine is given, it attains full effect 20 min after injection. Furthermore, the active morphine metabolites M3G and M6G appear rapidly in the circulation, which could influence the analgesic response to morphine treatment. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.
Journal Article↗
Perceived symptoms amongst hypertensive patients in routine clinical practice- a population-based study.
OBJECTIVES: To compare perceived symptoms between patients undergoing antihypertensive therapy and hypertensive patients without drug treatment, and to assess reasons for change of antihypertensive medication in routine clinical practice. DESIGN: Population-based multicentre study. Consecutive patients from a randomized sample of centres were given a standardized questionnaire to assess symptoms as well as opinions about their antihypertensive drugs. SETTING: Fifty-five Swedish primary health care centres and 11 clinics of internal medicine. PATIENTS: One thousand and thirteen hypertensive patients on their individually prescribed antihypertensive medication and 13 5 without antihypertensive therapy. MAIN OUTCOME MEASURES: Prevalence and perception of symptoms with and without antihypertensive drug therapy, changes of medication and reasons for this. RESULTS: Amongst the group of patients on antihypertensive medication, 57% spontaneously reported having had symptoms of high blood pressure before they started their drug therapy. Amongst the patients without antihypertensive drugs, 52% reported having such symptoms. When answering direct questions about different symptoms related to current drug treatment or increased blood pressure, patients with and without medication reported symptoms to a similar extent: 80 and 85%, respectively. A majority of patients (64%) had changed their medication during the course of treatment (range 0-61 years). The mean number of changes was 2.4 times over 12 years. The most common reported cause for changing drug treatment was side-effects (42%). CONCLUSIONS: The study shows that patients in general perceive symptoms from hypertension. Antihypertensive medication decreases the frequency and intensity of symptoms that might be related to high blood pressure but adds other symptoms linked to the medication. Changes in medication were mostly related to side-effects. The follow-up should pay attention to patients' experience of treatment. A sign of a well-managed hypertension population would be a decrease of symptoms over time.
Adult↗
Hypertension management in practice--priorities and problems.
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Humans↗
Measuring blood pressure in children and adolescents.
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Adolescent↗
Isolated systolic hypertension: an important cardiovascular risk factor.
Hypertension is an established risk factor for cardiovascular disease morbidity and mortality. Randomized trials of antihypertensive therapy have demonstrated the benefits of treating diastolic blood pressure, and recently the value of treating isolated systolic blood pressure has also been established. There is an excess risk of cardiovascular disease in subjects with borderline isolated systolic hypertension. In fact, data from men screened for the Multiple Risk Factor Intervention Trial show that the great majority of excess deaths are in those with high-normal systolic blood pressure or with stage 1 hypertension, i.e., systolic blood pressure 130 to 159 mmHg. Similarly, data from the Framingham Heart Study and the Physicians' Health Study emphasize the importance of mild elevations of systolic blood pressure. As age increases the hemodynamic patterns of blood pressure change due to an increase in large artery stiffness, and borderline isolated systolic hypertension becomes the dominant form of hypertension. These facts make the prevention and control of borderline isolated systolic hypertension a key strategic challenge in the effort to prevent excess mortality attributable to blood pressure levels above normal.
Adult↗
The growing importance of systolic blood pressure.
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Aging↗
The renin-angiotensin system--a century of progress.
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Animals↗
Treating hypertension--effect of treatment and cost-effectiveness in respect to later cardiovascular diseases.
A large number of prospective intervention trials have clearly demonstrated that drug treatment of hypertension lower cardiovascular morbidity and mortality. In the elderly, where treatment results in higher absolute decreases in morbidity and mortality, drug treatment is clearly cost-effective or even cost-saving in some groups of patients. Although the concept of treating hypertension is generally well accepted, a significant portion of patients remain insufficiently treated. In spite of major advances in the management of hypertension during the last decades, there is an excess morbidity and mortality in the hypertensive population. Thus, treatment is still imperfect, and a number of measures need to be taken in order to bring down cardiovascular risk in hypertensive patients to that of the normotensive population.
Adult↗
Myocardial turnover of endogenous opioids and calcitonin-gene-related peptide in the human heart and the effects of spinal cord stimulation on pacing-induced angina pectoris.
Earlier studies have shown that spinal cord stimulation (SCS) has antianginal and anti-ischemic effects in severe coronary artery disease. In the present study, 14 patients were subjected to right-sided atrial catheterization and atrial pacing. The patients were paced to angina during a control session and during spinal cord stimulation. Myocardial extraction of beta-endorphin (BE) during control pacing (8 +/- 22%) changed to release at the maximum pacing rate during treatment (-21 +/- 47%, a negative value representing release). Furthermore, the results indicate local myocardial turnover of leuenkephalin, BE and calcitonin-gene-related peptide. In addition, it is implied that SCS may induce myocardial release of BE which could explain the beneficial effects in myocardial ischemia.
Aged↗
Hypertension optimal treatment (HOT) study: home blood pressure in treated hypertensive subjects.
The Hypertension Optimal Treatment Study is a prospective trial conducted in 26 countries. The aims are to (1) evaluate the relationship between three levels of target office diastolic blood pressure (BP) (< or = 80, < or = 85, or < or = 90 mm Hg) and cardiovascular morbidity and mortality in hypertensive patients and (2) examine the effects on cardiovascular morbidity and mortality of 75 mg aspirin daily versus placebo. A total of 19,193 patients between 50 and 80 years of age had been randomized by the end of April 1994. Treatment was initiated with felodipine 5 mg daily, and additional therapy was given in accordance with a set protocol. The present substudy of 926 patients performed in nine countries aimed to (1) compare home with office BP in a representative subsample of the HOT population after the titration of treatment was completed and (2) clarify whether the separation into the target groups could be expanded into the out-of-office setting. The differences between office and home measurements in diastolic BP of 0.2 mm Hg (SD, 9; 95% confidence interval, -0.36 to 0.81; P=.40) and systolic BP of 0.5 mm Hg (SD, 15; 95% confidence interval, -0.53 to 1.46; P=.21) were not significant. The group differences in home BP were 1.9 mm Hg (< or = 80 versus < or = 85) and 1.2 mm Hg (< or = 85 versus < or = 90) for diastolic BP (F=11.69; ANOVA, P<.0001) and 2.6 and 2.1 mm Hg for systolic BP (F=8.44, P=.0002). Thus, office and home BPs measured with the same semiautomatic device are comparable in treated hypertensive subjects in the HOT Study, and the separation into the target groups based on office readings prevails at home.
Aged↗
Characteristics of 9194 patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint Reduction in Hypertension.
-Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (<17%) than in the general population, and approximately 7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal, <140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death.
Aged↗
Patients' and physicians' assessment of risks associated with hypertension and benefits from treatment.
BACKGROUND: Perceptions of effects of a medical regimen may affect patients' adherence to therapy. OBJECTIVE: To assess concordance between patients' and physicians' estimations of the risks of hypertension and benefits of treatment during a regular follow-up appointment. DESIGN: A population-based Swedish multicentre study. Patients were included consecutively from a randomized selection of centres (55 primary health care centres and 11 clinics of internal medicine). METHODS: A questionnaire was given to 1013 patients undergoing their individually prescribed antihypertensive therapy and 212 physicians who were caring for these patients. RESULTS: Without therapy, patients perceived the risks of cardiovascular complications to be higher than did their physicians. Patients were not aware that an increasing number of risk factors has an impact on the risk of complications. Patients furthermore rated the benefits of treatment higher than did their physicians (P<0.001). Of the patients, 14% had blood pressures < or = 140/90 mmHg. Most of the patients (61%) were not aware of their target blood pressure. However, when the target pressure was communicated to patients by the physician, patients remembered it accurately. The patients were generally not willing to trade even minor side effects from antihypertensive therapy for benefits of treatment. CONCLUSIONS: There was a high degree of inconsistency between patients' and physicians' estimations of risks of hypertension. Patients estimated the effects of treatment to be more beneficial than did their physicians.
Adult↗