Gender-related differences in left ventricular structural and functional responses to hypertension.
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Aged↗
Biomedical subjects
P A de Graeff
Publications and source records attributed to P A de Graeff.
Accelerated decline and prognostic impact of renal function after myocardial infarction and the benefits of ACE inhibition: the CATS randomized trial.
AIMS: Information regarding the cardiorenal axis in patients after a myocardial infarction (MI) is limited. We examined the change in renal function after a first MI, the protective effect of angiotensin converting enzyme (ACE) inhibition and the prognostic value of baseline renal function. METHODS AND RESULTS: The study population consisted of 298 patients with a first anterior wall MI who were randomized to the ACE inhibitor captopril or placebo after completion of streptokinase infusion. Renal function, by means of glomerular filtration rate (GFR), was calculated using the Cockroft-Gault equation (GFR(c)). In the placebo group, renal function (GFR(c)) declined by 5.5 min(-1)within 1 year, vs only 0.5 ml min(-1)in the ACE inhibitor group (P<0.05). This beneficial effect of captopril was most pronounced in patients with the most compromised renal function at baseline. The incidence of chronic heart failure (CHF) within 1 year increased significantly with decreasing GFR(c)(divided into tertiles: 24.0, 28.9, and 41.2%; P<0.01). The risk-ratio for GFR(c)<81 ml min(-1)vs >103 mL min(-1)was 1.86 (95% CI 1.11-3.13; P=0.019). CONCLUSIONS: Renal function markedly deteriorates after a first MI, but is significantly preserved by ACE inhibition. Furthermore, an impaired baseline renal function adds to the prognostic risk of developing CHF in patients after a first anterior MI.
Adult↗
[Diagnostic image (105). A woman with painful nodules. Infection with O. volvulus].
A 17-year-old woman from the Democratic Republic of Congo presented with painful nodules on the legs and malaise. An infection with Onchocerca volvulus was diagnosed.
Adolescent↗
Microalbuminuria is related to marked end organ damage in previously untreated, elderly hypertensive patients.
We wondered whether, in an elderly hypertensive population in a primary prevention setting, free from diabetes mellitus and clinical atherosclerosis, differences between end organ damage and microalbuminuria (MA) could be found using a lower level of urinary albumin excretion than that of classically defined MA. From a population survey of 173 previously untreated hypertensive patients (4x blood pressure systolic > or = 160 and < or = 220 mmHg, and/or diastolic > or = 95 and < or = 115 mmHg), mean age 67 +/- 4 years, were screened for MA (defined as albumin excretion between 20 and 300 mg/24 h). End organ damage was determined by B-mode ultrasound scanning of carotid and femoral arteries and echocardiography. Out of 173 hypertensives, 14 showed MA (8%). These hypertensives had a significantly higher intima media thickness (IMT; 1.01 +/- 0.21 vs 0.88 +/- 0.6 mm, p < 0.05) and increased left ventricular mass index (118 +/- 31 vs 103 +/- 22 g/m2, p < 0.05) than hypertensives without MA. Linear regression analysis showed that MA, age, male gender and diastolic blood pressure were independently related to IMT, while systolic blood pressure, male gender and body mass index were independently related to left ventricular mass. Even using lower levels of urinary albumin excretion rate, patients with MA had significantly higher IMT and increased left ventricular mass. Moreover, MA was independently related to IMT in these elderly hypertensives. These results suggest that the threshold value for MA should be reconsidered in hypertension.
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Comparative trials in registration files of cardiovascular drugs: comparator drugs and dosing schemes.
Registration files of 13 cardiovascular drugs were analysed with respect to the number of double-blind phase-III clinical trials, the use of placebo and active comparator drugs and their dosing schemes. Half of the 146 double-blind trials used active comparator drugs. The majority of files included first-choice reference drugs, but we also found trials in three files with lower dosing schemes of comparator drugs and four files which included only placebo or active controlled double-blind trials. To allow a better interpretation of the information provided in European Public Assessment Reports, which are published for every product approved for marketing in the European Union, uniform reporting is recommended on basic details of trial design, such as comparator drugs used and dosing schemes.
Cardiovascular Agents↗
Long-term effects of amlodipine and lisinopril on left ventricular mass and diastolic function in elderly, previously untreated hypertensive patients: the ELVERA trial.
OBJECTIVE: To compare the effects of a calcium antagonist (amlodipine) and an angiotensin converting enzyme inhibitor (lisinopril) on left ventricular mass and diastolic function in elderly, previously untreated hypertensives. DESIGN: A double-blind randomized parallel group trial. Effects of amlodipine and lisinopril on left ventricular mass and diastolic function (E/A Ratio) (The ELVERA trial). SETTING: Rural northern Netherlands: population screening new diagnosed hypertensive subjects. PATIENTS: The study population comprised 166 newly diagnosed hypertensive (aged 60-75) with diastolic blood pressure between 95-115 mmHg and/or systolic blood pressure between 160-220 mmHg. INTERVENTION: Patients were randomly allocated to receive 5-10 mg amlodipine or 10-20 mg lisinopril for 2 years. MAIN OUTCOME MEASURES: Prior and after 1 and 2 years of treatment left ventricular mass, indexed by body surface (LVMI) was estimated by 2-D mode echocardiography according to Devereux with use of Penn convention. Early to atrial filling ratio (E/A) was assessed by transmitral flow. Change from baseline of LVMI and E/A ratio was evaluated by repeated measurement analysis of the treatment effect in an intention-to-treat analysis. RESULTS: Both amlodipine and lisinopril led to equivalent reduction in systolic and diastolic blood pressure. At the end of the study the amlodipine group led to LVMI decrease by 21.8 g/m < or = [95% confidence interval (CI), 18.3-25.3] and E/A ratio increased by 0.08 (95% CI, 0.05-0.11). In the lisinopril group LVMI decreased by 22.4 g/m < or = (95%, CI, 19.0-25.8) and E/A ratio increased by 0.07 (95% CI, 0.04-0.10). No statistically significant differences were found in changes in LVMI and E/A ratio between amlodipine and lisinopril. CONCLUSION: A long-term study, the ELVERA trial proves that amlodipine and lisinopril reduce left ventricular mass and improve diastolic function to a similar extent in elderly newly diagnosed hypertensive patients.
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Reversal of pathophysiologic changes with long-term lisinopril treatment in isolated systolic hypertension.
The purpose of this study was to evaluate in a prospective, double-blind, placebo-controlled study the effect of long-term (2-year) lisinopril treatment on cardiovascular end-organ damage in patients with previously untreated isolated systolic hypertension (ISH). All patients with ISH were derived from a population screening program. End-organ damage measurements, done initially and after 6 and 24 months of treatment, included measurements of aortic distensibility and echocardiographic left ventricular mass index (LVMI) and diastolic function. Blood pressure was measured by office and ambulatory measurements. Of the 97 subjects with ISH selected from the screening, 62 (30 lisinopril) completed the study according to protocol. Office blood pressure decreased in both groups, but ambulatory results significantly decreased with lisinopril-treatment only. Aortic distensibility increased significantly with lisinopril, as opposed to a decrease in placebo-treated subjects. The main effect of increased distensibility occurred between 6 and 24 months, whereas ambulatory blood pressure changed mainly in the first 6 months of treatment. LVMI decreased in both treatment groups, with a significantly higher reduction in lisinopril-treated subjects. Left ventricular diastolic function showed no significant changes in either group. The vascular pathophysiologic alterations of ISH-a decreased aortic distensibility-can be improved with long-term lisinopril treatment, whereas values deteriorate further in placebo-treated subjects. These results, in one of the first studies including subjects with previously untreated ISH only, indicate that lisinopril treatment might favorably influence the cardiovascular risk of ISH.
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Silent ST depression and cardiovascular end-organ damage in newly found, older hypertensives.
In hypertension, both reduced vascular supply and increased cardiac demand contribute to the development of (silent) myocardial ischemia. Our aim was to determine the prevalence of ST-segment depression and to analyze contributing factors in asymptomatic, previously untreated, older hypertensives. From a population survey, in 184 patients with mild hypertension (4 times systolic blood pressure >/=160 mm Hg and/or diastolic blood pressure >/=95 mm Hg), 60 to 75 years of age, cardiovascular end-organ damage was measured. Episodes of ST-segment depression were measured by 48-hour ambulatory Holter monitoring and were observed in 21 hypertensives (12%). They showed a significantly higher combined far-wall intima-media thickness of carotid and femoral arteries and more arterial plaques as measured by B-mode ultrasound compared with hypertensives without ST depression (0.00098+/-0.00021 versus 0.00088+/-0.00016 mm and 5.2+/-3.7 versus 3.7+/-2.8 plaques, P<0.05, respectively), whereas left ventricular mass index was not different (111+/-18 versus 104+/-24 g/m(2); P=0.18, respectively). In hypertensives with transient ST-segment depression, a significant relation was found between left ventricular mass and ischemic burden (r=0.51, P=0.02). Approximately 1 of 8 unselected and previously untreated older hypertensives show asymptomatic ST-segment depression, suggestive of silent myocardial ischemia. These data suggest that vascular factors mainly determine the occurrence of ischemic ST-segment depression and cardiac factors determine the ischemic burden in older hypertensives.
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Assessment of new cardiovascular drugs. Relationships between considerations, professional characteristics, and prescribing.
OBJECTIVES: To study considerations used by professional and academic leaders to assess the position of new cardiovascular drugs in the therapeutic regimen in relationship to professional characteristics and the level of prescribing. METHODS: Interviews with 39 internists, cardiologists, general practitioners, and hospital pharmacists about considerations regarding the therapeutic position and prescribing of a new cardiovascular drug (losartan or atorvastatin) and professional characteristics. Considerations were classified according to Rogers' characteristics of an innovation, i.e., referring to the drug's relative advantage, compatibility, or complexity. Proportions of respondents mentioning advantageous, comparable, and/or disadvantageous characteristics were used to construct patterns to analyze an overall evaluation of the drugs in relation to professional characteristics and level of prescribing. RESULTS: The majority of considerations referred to the degree of relative advantage, but different subjects were emphasized for both drugs. Overall patterns of evaluation were generally intermediate and negative. The respondents' profession, mentioning commercial sources of information and self-qualification as a (moderately) early adopter of new drugs differentiated the overall evaluation of the drugs, in contrast to expertness and academic affiliation. The level of prescribing differentiated the overall evaluation only in the case of losartan. CONCLUSIONS: These professional and academic leaders critically evaluated the claims when assessing the position of the drugs in the therapeutic regimen but did not show consensus in their considerations. Accepted principles for prescribing were considered when assessing the therapeutic position of the drugs but resulted in varied tendencies for prescribing.
Cardiovascular Agents↗
[Clinical evaluation of efficacy and adverse effects in the (European) registration of drugs: what does it mean for the doctor and patient?].
The clinical criteria for admission of new drugs to the European common market have become more stringent in recent years. Increasingly often, the manufacturer is required to demonstrate that the new drug offers a clinically visible and relevant benefit to the patient. Efficacy and adverse effects should not only be studied by comparative trials with placebo, the registration authorities also expect the drug to be compared with the standard treatment already available. Such trials should prove that the balance between efficacy and adverse effects of the drug is better than that of placebo and at least as good as the standard treatment, as regards not only statistical significance but also clinical relevance. Therefore, Dutch and European assessment reports and product information may be increasingly useful to prescribers, patients and insurers in determining the role and therapeutic value of new drugs within the existing therapeutic possibilities concerning certain diseases.
Clinical Trials as Topic↗
Co-morbidity of 'clinical trial' versus 'real-world' patients using cardiovascular drugs.
PURPOSE: To examine discrepancies between co-morbidity of patients included in pre-marketing clinical trials of cardiovascular drugs and patients from daily practice, representing the actual users after marketing, and to investigate the availability of data regarding co-morbidity in registration files. METHODS: Data were collected from phase III trials of registration files of 16 drugs, registered in the Netherlands in the period 1985 through 1994 for the indications hypertension, angina pectoris or hypercholesterolemia, and from a general practitioners database. Patients were selected who used drugs from the same therapeutic classes for the same indication as the patients in the pre-marketing trials. Prevalences of concomitant cardiovascular, endocrine and metabolic diseases were compared between pre- and postmarketing populations. Discrepancies were defined as more than 10% difference in prevalences. RESULTS: Data regarding co-morbidity were present in 13 out of 16 registration files and differed in format of reporting. For all indications, coexisting cardiovascular, endocrine and metabolic diseases were less prevalent in the pre-marketing populations, except ischemic heart disease, which was more prevalent coexisting with angina pectoris and hypercholesterolemia. Discrepancies were found for hypertensive disease, heart failure, diabetes mellitus and myocardial infarction. CONCLUSIONS: Phase III trials testing cardiovascular drugs included patients with concomitant cardiovascular, endocrine and metabolic diseases, but discrepancies were present with patients in daily practice. Development of guidelines for uniform collection and reporting of co-morbidity data in pre-marketing trials is recommended, as well as further utilization of data.
Angina Pectoris↗
Predictors for prophylactic antithrombotic prescribing in ischaemic heart disease and the impact of national guidelines.
OBJECTIVES: Assessment of predictors for initiating prophylactic antithrombotic prescribing for patients newly diagnosed with ischaemic heart disease (IHD) and the impact of the introduction of national guidelines. DESIGN AND SETTING: A retrospective case-control study was performed using pharmacy prescription data from 120,000 Dutch patients over a 5-year period. IHD patients were identified using as a marker multiple nitrate prescriptions [anatomical-chemical-therapeutic (ATC) code CO1D] indicating chronic use. Initiation of antithrombotic therapy was likewise identified using ATC codes B01AA and B01AC (oral anticoagulants and thrombocyte aggregation inhibitors), prescribed within 6 months following the first nitrate prescription. Statistically significant (P<0.05) predictors were assessed using multivariable analysis considering patient, prescriber and medication characteristics. RESULTS: Of the 2598 patients who met specified inclusion criteria for newly diagnosed IHD, approximately 35% was not prescribed any type of antithrombotic therapy. Male patients [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.0-2.9], patients with cardiovascular (other than IHD) and diabetic co-morbidity (OR 6.4, 95% CI 4.8-7.9 and OR 1.6, 95% CI 1.1-2.1, respectively) and patients using isosorbide mononitrate rather than isosorbide dinitrate as anti-ischaemic main therapy (OR 2.1, 95% CI 1.3-2.5) were most likely to be prescribed antithrombotic therapy. Furthermore, initiating antithrombotic prescribing was more likely after the introduction of national guidelines (OR 1.4, 95% CI 1.1-1.7). CONCLUSIONS: Initiating antithrombotic prescribing in newly diagnosed IHD patients can be predicted by patient gender, certain co-morbidity and main type of nitrate therapy. The introduction of national guidelines has resulted in an increase of prophylactic antithrombotic prescribing in accordance with their contents.
Adult↗
[Role of cytochrome P450 enzymes in pharmaceutical preparations].
Cytochrome P450 enzymes are responsible for pharmacokinetic interactions with sometimes serious adverse effects. If a drug is known to be a substrate, inhibitor or inducer of one of the cytochrome P450 isoenzymes, it can be estimated with which other drugs it will interact. The interaction profile of a new drug plays an increasing role in the assessment of the benefit/risk ratio by regulatory authorities. Interactions in practical situation can, however, never be ruled out without proper precautions of both pharmacists and physicians. More attention for the possible occurrence of interactions and searching for a good alternative for one of the drugs to be used should lead to a reduction in the number of adverse events related to interactions.
Cytochrome P-450 Enzyme Inhibitors↗
[Risk factors for dying among ibopamine users].
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Adult↗
Cardiovascular drugs: discrepancies in demographics between pre- and post-registration use.
OBJECTIVES: To study discrepancies in demographic characteristics between patients participating in pre-registration phase III trials of cardiovascular drugs, registered in the Netherlands, and patient populations in daily practice representing the actual users of the drugs after registration. METHODS: Comparison of age and sex distribution in registration files of 15 cardiovascular drugs [angiotensin-converting enzyme (ACE)inhibitors/angiotensin II receptor antagonists, calcium channel blockers, beta-adrenergic blocking agents, vasodilators, HMG-CoA reductase inhibitors and thrombolytics] with patients selected from a general practitioner (GP) registration database, who had received prescriptions for drugs from the therapeutic classes for the registered indications (hypertension, hypercholesterolaemia or angina pectoris) or were diagnosed with myocardial infarction. Moderate discrepancy was defined as more than 10% difference between the populations, large discrepancy by more than 20% difference. Clinical trials were also analysed by region of trial performance with respect to patient selection criteria, differences in male/female ratios and ethnic origin of patients. RESULTS: Phase III clinical trials in registration files of drugs registered for hypertension, angina pectoris and myocardial infarction had a moderate to large under-representation of female patients. Patients aged more than 65 years, who accounted for more than 50% of drug use indicated for hypertension, angina pectoris and myocardial infarction, were under-represented in the clinical trials of drugs registered for all indications. Trials performed in North America included relatively fewer female patients compared with European trials, and showed different patterns in the ethnic origin between indications. CONCLUSIONS: Clinically relevant subgroups of cardiovascular patients are under-represented in pre-registration phase III trials. These findings concern major areas of cardiovascular diseases, i.e. hypertension, hypercholesterolaemia, angina pectoris and myocardial infarction. Widely used therapeutic classes of drugs are affected and regional differences in trial performance are present.
Adult↗
Home blood pressure measurement: reproducibility and relationship with left ventricular mass.
OBJECTIVE: To evaluate the reproducibility and relationship with left ventricular mass index of home blood pressure in comparison with ambulatory and office blood pressures. METHODS: We measured home, ambulatory and office blood pressures of 84 previously untreated hypertensive patients, aged 60-74 years, from primary care, at baseline and after 12 weeks, without active intervention in between. Left ventricular mass index was determined echocardiographically during week 12. RESULTS: Decreases in systolic and diastolic blood pressures were found after 12 weeks for mean home and office blood pressures (P<0.05), but not for mean ambulatory blood pressure. The coefficients of reproducibility for systolic and diastolic ambulatory blood pressures were 26.4 and 16.0, respectively. Correlation coefficients for correlation of left ventricular mass index to ambulatory blood pressure (0.51 and 0.36) were higher than the correlation coefficients for home (0.31 and 0. 16) and office (0.32 and 0.21) blood pressures, for systolic and diastolic values, respectively. However, we could find no statistically significant difference among the correlation coefficients for all three types of measurements. CONCLUSIONS: Home blood pressure was considerably less reproducible than ambulatory blood pressure and no different from office blood pressure in this respect. The relationship with left ventricular mass index appeared to be stronger for ambulatory than it was for home and office blood pressures, although not statistically significant so.
Aged↗
Effect of quinapril and triamterene/hydrochlorothiazide on cardiac and vascular end-organ damage in isolated systolic hypertension.
We compared, in a prospective double-blind randomized study, the effect of the angiotensin-converting enzyme inhibitor quinapril (QUI) with that of triamterene/hydrochlorothiazide (THCT) treatment on cardiovascular end-organ damage in subjects with untreated isolated systolic hypertension (ISH). End-organ damage measurements, performed initially and after 6 and 26 weeks of treatment, included echocardiographic determination of left ventricular mass index (LVMI) and of diastolic function and measurement of aortic distensibility and peripheral vascular resistance. Blood pressure was significantly reduced in the 44 subjects (21 QUI, 23 THCT) completing the study. Both LVMI and aortic distensibility had changed at 6 weeks, with comparable improvements in both groups. LV diastolic function showed overall no significant changes, although patterns of early filling did differ between the two drug groups. Peripheral vascular resistance appeared to increase between 6 and 26 weeks in THCT subjects only, along with a decreased aortic distensibility. Blood pressure and LV mass were rapidly and markedly reduced in both treatment groups of ISH subjects, paralleled by an improvement of aortic distensibility. In interpreting these results, the pathophysiologic alterations in ISH need to be taken into account, because these differ strongly from those in diastolic hypertension. Results of LV diastolic function and peripheral vascular resistance were less clear but appear to show less favorable changes in the THCT subjects treatment group.
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Effects of amlodipine and lisinopril on left ventricular mass and diastolic function in previously untreated patients with mild to moderate diastolic hypertension.
The aim of the study was to compare the effects of two long-acting antihypertensive agents, the calcium-antagonist amlodipine and the ACE inhibitor lisinopril, on left ventricular mass and diastolic filling in patients with mild to moderate diastolic hypertension from primary care centres. It is a 1-year prospective, double-blind, randomized, parallel group, comparative study. Patients between 25 and 75 years of age with untreated hypertension with elevated diastolic blood pressure (> or = 95 mmHg) on three occasions (twice on the first visit and once only on the second and third visits) were recruited from a population survey. After 4 weeks placebo run-in 71 patients were randomized to dosages of amlodipine 5-10 mg or lisinopril 10-20 mg, which were titrated on the basis of the effects on blood pressure. Fifty-nine patients completed the study period. Primary endpoints were left ventricular mass index and early to atrial peak filling velocity. Office and ambulatory blood pressure and other echocardiographic measurements were considered secondary. Decrease in blood pressure was equal for both treatment regimens. A statistically significant decrease in left ventricular mass index in both treatment groups was observed: -11.0 g/m2 (95% CI: -6.0, -16.1) in the amlodipine group and -12.6 g/m2 (95% CI: -8.2, -17.0) in the lisinopril group. The higher the baseline value of left ventricular mass before treatment, the more the decrease after treatment. Early to atrial peak filling velocity did not change significantly within the treatment groups: +0.07 (95% CI: -0.01, +0.15) in the amlodipine group and +0.01 (95% CI: -0.06, +0.08) in the lisinopril group. However, analysis of time measurements of the early peak showed significant changes for both treatment groups. No significant differences in primary and secondary endpoints between treatment groups were found. Twelve patients did not complete the study, seven in amlodipine and five in lisinopril, basically due to adverse events. The effects of amlodipine and lisinopril on left ventricular mass and early to atrial filling peak velocity after 1 year of treatment in patients with previously untreated mild to moderate hypertension are similar. Further studies are recommended, particularly with a larger sample size and a follow-up of longer duration.
Adult↗