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Biomedical subjects

A A Kroon

Publications and source records attributed to A A Kroon.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of brain natriuretic peptide on forearm vasculature: comparison with atrial natriuretic peptide.

OBJECTIVE: The aim of the present study was to determine the vasoactive effects of brain natriuretic peptide (BNP) as compared to those of atrial natriuretic peptide (ANP) in normal man. METHODS: Ten healthy male subjects (median age 21 (20-23) year) were studied twice. In the first study equimolar doses (1, 3, and 10 pmol/dl/min) of both BNP and ANP (in random order and double blind) were infused into the brachial artery of the non-dominant arm with a 1-h wash-out period in between. In the second study two BNP (n = 5) or ANP (n = 5) dose-response curves were performed in order to assess the repeatability of the BNP/ANP infusions. To this end, BNP and ANP were infused in the same equimolar doses as in the first protocol. Forearm blood flow (FBF) was determined by venous occlusion plethysmography before and during infusions. RESULTS: BNP increased the FBF ratio (infused/contralateral arm) by 6%, 17%, and 48%, respectively (p < 0.05), while ANP increased the FBF ratio by 4%, 58%, and 133% (p < 0.001). The slopes of the BNP dose-response curves differed significantly from those of the ANP curves (18.1 versus 43.2; p = 0.022). No differences were observed between the repeated dose-response curves of either BNP or ANP. CONCLUSIONS: The present data demonstrate that BNP induces a dose-dependent vasodilatation in man. On a molar basis, however, this vasodilatation is significantly less than the vasodilatation induced by ANP. These differences may be related to differences in natriuretic-peptide-receptor affinity. Furthermore, our data show that the vasoactive effects of both BNP and ANP are repeatable in time.

Adult↗
PubMed1998

[The relationship between genetic polymorphisms and disease, illustrated by the renin-angiotensin-aldosterone system and cardiovascular disease].

The role of molecular genetics in the pathophysiology of various diseases is becoming clearer and clearer. In the field of cardiovascular diseases, molecular genetic aspects have been shown to play a definite role in the aetiology of these diseases. Several molecular-genetic variations called polymorphisms, occur in the population. The genes encoding the different components of the reninangiotensin-aldosterone system (RAAS), an important system in the regulation of the function and structure of the heart and vascular wall, also display polymorphisms. For some of these polymorphisms associations with various cardiovascular and renal diseases have been described. At present, this is particularly clear for the relation between angiotensin-converting-enzyme (ACE) polymorphism and the incidence of atherosclerotic complications and diabetic nephropathy, and for the relation between so-called M235 T-variant of the angiotensinogen gene and hypertension. Future research will have to show where it is worthwhile to use these and other polymorphisms as a marker for genetic risk. In what way the different RAAS-polymorphisms relate to functional abnormalities is as yet unclear, as are the potential therapeutic implications.

Angiotensin II↗
PubMed1998

Hypertension and the development of heart failure.

Hypertension is a well-known risk factor that predisposes to the development of left ventricular hypertrophy, coronary flow abnormalities, and systolic and diastolic dysfunction. This complex of abnormalities is known as hypertensive heart disease and eventually leads to heart failure. Structural lesions underlying this process include excess deposition of collagens and cellular infiltration, with an increase in the size of cardiac myocytes (remodeling). The occurrence of arteriolar lesions may lead to impediments of flow. Clinically, hypertensive heart disease manifests itself by anginal complaints and sometimes by silent ischemia, arrhythmias, and sudden death. Alterations in systolic and/or diastolic function may be associated with symptoms of heart failure. Although successful treatment of hypertension can probably retard the process of cardiac impairment, there is as yet no evidence that heart failure can be prevented.

Antihypertensive Agents↗
PubMed1998

Adenosine-induced renal vasodilatation is prolonged in renal artery stenosis.

OBJECTIVE: The objective of this study was to determine whether the response of renal blood flow (RBF) to adenosine infusions differs between hypertensive patients with and without renal artery stenosis (RAS). DESIGN AND METHODS: Twenty-one hypertensive patients who underwent diagnostic angiography of the renal arteries were studied. Nine patients (median age 51 years; 45-61 interquartile ranges) were diagnosed as having essential hypertension (EH). Twelve patients (median age 52 years; 50-58) had hypertension and renal artery stenosis. In all patients three stepwise increasing doses of adenosine (1, 3 and 10 (microg/kg/min) were infused into the renal artery. RBF was measured before and during infusions by means of the 133xenon wash-out method. Arterial and venous plasma samples for renin concentration were obtained from the renal artery and renal vein. Intraarterial blood pressure and heart rate were monitored continuously. RESULTS: Both groups were similar with respect to age, body mass index, mean arterial pressure and baseline RBF (EH: median 428; RAS 343 ml/min/100 g). Both groups showed a similar dose-related increase in RBF during adenosine infusions (normal kidneys: 9, 21 and 34% change vs baseline; stenotic kidneys: 16, 39 and 52% change vs baseline). Ten minutes after discontinuation of the adenosine infusion, RBF returned to baseline in the normal kidney group, but increased further in the stenotic kidney group (71% vs baseline; P = 0.033). Adenosine infusion did not affect the renin secretion in either group. CONCLUSION: Both essential hypertensive patients and patients with renal artery stenosis show a dose-dependent vasodilatation following adenosine infusion. This vasodilatation is sustained after discontinuation of the adenosine infusion in patients with renal artery stenosis, suggesting a potentiated mechanism for vasodilatation induced by adenosine.

Adenosine↗
PubMed1997

LDL-cholesterol lowering and atherosclerosis--clinical benefit and possible mechanisms: an update.

The results of several lipid-lowering randomized trials have been released during the past years and have confirmed the lipid hypothesis. Reduction of cholesterol by potent drugs in clinically symptomatic or asymptomatic patients with above-average cholesterol levels will substantially reduce the risk of coronary events. The present article gives a review of potent low-density lipoprotein cholesterol-lowering treatments and discusses developments in hypolipidaemic therapy in relation to recent primary and secondary prevention studies. In addition, possible mechanisms of cholesterol lowering in retardation of the atherosclerotic process are summarised.

Animals↗
PubMed1997

Fixed low-dose combination of an angiotensin converting enzyme inhibitor and a calcium channel blocker drug in the treatment of essential hypertension.

AIM: To review the possibilities of combination treatment in hypertension with special emphasis on the combination of an angiotensin converting enzyme (ACE) inhibitor and a calcium channel blocker. RESULTS: An increasing number of combination of drugs has become available. Fixed combinations, often low-dose, have proved suitable for the treatment of hypertension, even as first-line therapy. CONCLUSION: A fixed combination of an ACE inhibitor and a calcium channel blocker, in particular the combination of trandolapril and verapamil, is a suitable alternative to existing treatment modalities.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Aggressive lipid lowering treatment in coronary atherosclerosis.

Reduction of cholesterol by potent drugs in clinically symptomatic or asymptomatic patients with elevated cholesterol levels will substantially decrease the risk of coronary events. In selected cases more aggressive treatment of hyperlipidemia is necessary, such as in patients, homozygous for familial hypercholesterolemia, or subjects with severe coronary artery disease who are refractory to diet and drugs. LDL-apheresis, by which atherogenic lipoprotein particles are removed from the blood extracorporeally, is a therapeutic option in these cases. In this report a study is summarized, in which the effect of intervention with LDL-apheresis plus simvastatin was compared with conventional drug treatment alone in a group of patients with severe coronary artery disease with respect to changes in coronary atherosclerotic lesions and their functional impact.

Adult↗
PubMed1996

Effect of apheresis of low-density lipoprotein on peripheral vascular disease in hypercholesterolemic patients with coronary artery disease.

BACKGROUND: Apheresis of low-density lipoprotein (LDL) is an effective lipid-lowering treatment in hypercholesterolemic patients who have coronary artery disease and are refractory to drugs. More aggressive lipid-lowering therapy may further slow the progression of atherosclerosis. OBJECTIVE: To compare the effect of LDL apheresis and simvastatin therapy with the effect of simvastatin therapy alone on the progression of peripheral vascular disease. DESIGN: Open, randomized, single-center study. SETTING: University hospital. PATIENTS: 42 men with primary hypercholesterolemia (total cholesterol level > 8.0 mmol/L) and extensive coronary atherosclerosis. INTERVENTION: Biweekly apheresis of LDL plus simvastatin, 40 mg/d (n = 21), or simvastatin, 40 mg/d (n = 21), for 2 years. MEASUREMENTS: Lipid and lipoprotein levels, changes in hemodynamically significant stenoses in the aortotibial tract (measured by ankle:arm systolic blood pressure ratio combined with Doppler spectrum analysis of the femoral artery), and changes in the mean intima-media thickness of three carotid artery segments. RESULTS: Mean baseline LDL cholesterol levels decreased from 7.8 to 3.0 mmol/L in the apheresis and simvastatin group and from 7.9 to 4.1 mmol/L in the simvastatin-only group; mean lipoprotein(a) levels decreased from 57.0 to 44.5 mg/dL (change, -19%) in the former group and increased from 38.4 to 44.5 mg/dL (change, 15%) in the latter group. In the apheresis group, the number of patients with hemodynamically significant stenoses in the aortotibial tract decreased from 9 to 7; in the simvastatin-only group, the number increased from 6 to 13 (P = 0.002). Mean intima-media thickness decreased by a mean +/- SD of 0.05 +/- 0.34 mm in the apheresis group and increased by 0.06 +/- 0.38 mm in the simvastatin-only group (P < 0.001). According to multiple regression analysis, changes in apolipoprotein B, total cholesterol, and lipoprotein(a) levels accounted for changes in the aortotibial tract (R2 = 0.36); changes in lipoprotein(a) and apolipoprotein A1 levels accounted for changes in the intima-media thickness of the carotid artery (R2 = 0.49). CONCLUSIONS: Aggressive lipid lowering with simvastatin and LDL apheresis decreased the intima-media thickness of the carotid artery and prevented an increase in the number of hemodynamically significant stenoses in the lower limbs. Therapy with simvastatin alone did not prevent progression of carotid or aortotibial vascular disease.

Adult↗
PubMed1996

LDL-Apheresis Atherosclerosis Regression Study (LAARS). Effect of aggressive versus conventional lipid lowering treatment on coronary atherosclerosis.

BACKGROUND: Intensive lipid lowering may retard the progression of coronary atherosclerosis. LDL-apheresis has the potential to decrease LDL cholesterol to very low levels. To assess the effect of more aggressive lipid lowering with LDL-apheresis, we set up a randomized study in men with hypercholesterolemia and severe coronary atherosclerosis. METHODS AND RESULTS: For 2 years, 42 men were treated with either biweekly LDL-apheresis plus medication or medication alone. In both groups a dose of simvistatin of 40 mg per day was administered. Baseline (mean+/-SD) LDL cholesterol was 7.8+/-1.9 mmol x L(-1) and 7.9+/-2.3 mmol x L(-1) in the apheresis and medication groups, respectively. The mean reduction in LDL cholesterol was 63% (to 3.0 mmol x L(-1)) and 47% (to 4.1 mmol x L(-1)), respectively. Primary quantitative coronary angiographic end points were changes in average mean segment diameter and minimal obstruction diameter. No differences between the apheresis and medication groups were found in mean segment diameter (-0.01+/-0.16 mm versus 0.03+/-0.16 mm, respectively) or in minimal obstruction diameter (0.01+/-0.13 mm versus 0.01+/-0.11 mm, respectively), expressed as means per patient. On the basis of coronary segment, mean percent stenosis of all lesions showed a tendency to decrease; only in the apheresis group more minor lesions disappeared in comparison to the medication group. On bicycle exercise tests, the time to 0.1 mV ST-segment depression increased significantly by 39% and the maximum level of ST depression decreased significantly by 0.07 mV in the apheresis group versus no changes in the medication group. CONCLUSIONS: Two years of lipid lowering both with medication alone or LDL-apheresis with medication showed angiographic arrest of the progression of coronary artery disease. However, more aggressive treatment induced functional improvement, which may precede anatomic changes.

Adult↗
PubMed1996

Low density lipoprotein apheresis improves regional myocardial perfusion in patients with hypercholesterolemia and extensive coronary artery disease. LDL-Apheresis Atherosclerosis Regression Study (LAARS).

OBJECTIVES: In a randomized study we evaluated the effect of biweekly low density lipoprotein (LDL) apheresis plus simvastatin versus medication alone on regional myocardial perfusion. BACKGROUND: In patients with severe hypercholesterolemia, diet and lipid-lowering drugs are often insufficient to achieve optimal LDL cholesterol values. Low density lipoprotein apheresis is a very effective lipid-lowering therapy. Assessment of regional myocardial perfusion enables evaluation of the functional state of the coronary circulation. METHODS: We studied 42 patients with severe hypercholesterolemia and extensive coronary artery disease who were randomized to diet and simvastatin with or without biweekly LDL apheresis. Regional myocardial perfusion was assessed by digital subtraction angiography with videodensitometric calculation of hyperemic mean transit time (HMTT) of contrast medium at baseline and after 2 years of therapy. RESULTS: Low density lipoprotein cholesterol decreased by 63% (to 3.0 mmol/liter) in the LDL apheresis group and by 47% (to 4.1 mmol/liter) in the medication group. Paired HMTT measurements were assessed in 43 regions in the LDL apheresis group and 35 regions in the medication group. In the LDL apheresis group, regional HMTT decreased over 2 years from 3.35 +/- 1.18 (mean +/- SD) to 2.87 +/- 0.82 s (-14%, p = 0.001), whereas no change in the medication group was observed: 2.95 +/- 1.06 to 2.96 +/- 0.90 s (p = NS). In the patient-based comparison, the mean change in HMTT was -0.45 s (-14%, p = 0.01) in the LDL apheresis group and -0.05 s (-2%, p = NS) in the medication group, respectively. Only exercise-induced ischemia improved in the LDL apheresis group. CONCLUSIONS: Biweekly LDL apheresis plus simvastatin decreased time-averaged LDL cholesterol levels by an additional 31% (1.1 mmol/liter) compared with medication alone. After 2 years of therapy, regional myocardial perfusion improved in the LDL apheresis group and remained unchanged in the medication group. Thus, aggressive reduction of LDL cholesterol has a favorable effect on regional myocardial perfusion and alleviates ischemia.

Adult↗
PubMed1996

Lissencephaly with extreme cerebral and cerebellar hypoplasia. A magnetic resonance imaging study.

A newborn with a rare type of lissencephaly is reported, characterized by extreme cerebral and cerebellar hypoplasia. The diagnosis was made by postmortem magnetic resonance imaging, indicating the value of such studies to evaluate neuronal migration disorders in patients in whom autopsy cannot be performed. Two earlier described microlissencephaly syndromes, the "Barth" and "McComb" type, are reviewed.

Cerebellum↗
PubMed1995

Long-term experience (6 years) with simvastatin in patients with heterozygous familial hypercholesterolaemia.

OBJECTIVE: To study the long-term efficacy and safety of the cholesterol synthesis inhibitor, simvastatin, in the treatment of familial hypercholesterolaemia. METHODS: This is an open long-term follow-up of patients treated for 5 years or more in the Nijmegen University lipid clinic. Forty-four patients with heterozygous familial hypercholesterolaemia (mean baseline serum cholesterol level 11.5 mmol/l) were treated with simvastatin alone (monotherapy group) in doses ranging from 20 to 80 mg/day, or in combination with other lipid-lowering agents (combination-therapy group). RESULTS: Over the intervention period of 6 years the mean overall reduction of the serum cholesterol level was 37.8% for the total group, 37.7% for the monotherapy group and 42.6% for the combination-therapy group. The reduction of the low-density lipoprotein (LDL)-cholesterol in the three groups was 45.0, 44.6 and 50.3%, respectively. The serum triglyceride concentration was reduced by 14.0, 20.5 and 12.5%, respectively. The increase in the high-density lipoprotein (HDL)-cholesterol level was 14.4, 16.2 and 14.0%, respectively. One patient died from a myocardial infarction and 2 patients had a non-fatal cardiac event. Two patients stopped taking medication due to side-effects (dizziness and insomnia). Biochemical adverse effects were confined to elevations of the alanine aminotransferase level and the creatine phosphokinase level and did not lead to discontinuation of therapy. CONCLUSIONS: Simvastatin proves to be a safe and effective lipid-lowering drug during long-term treatment.

Adult↗
PubMed1995

The prevalence of peripheral vascular disease in familial hypercholesterolaemia.

OBJECTIVES: In patients with familial hypercholesterolaemia (FH), the prevalence of haemodynamically significant peripheral vascular disease (PVD) was measured in relation to lipoproteins, general risk factors and the presence of coronary artery disease (CAD). DESIGN: A case control study. SETTING: The outpatient lipid clinic of a university hospital (tertiary referral centre). SUBJECTS: Patients with heterozygous FH [n = 68; age 45.8 +/- 11.6 years; untreated LDL-cholesterol 9.2 +/- 2.0 mmol L-1] were compared with control subjects matched for gender, age, weight, smoking and presence of hypertension [n = 27; age 44.0 years; LDL-cholesterol 3.8 +/- 1.3 mmol L-1]. MAIN OUTCOME MEASURES: PVD was assessed during cholesterol-lowering treatment using ankle/arm blood pressure ratios and analyses of Doppler-derived blood flow velocities in the femoral artery at rest and during reactive hyperaemia. The diagnosis of CAD was assessed clinically. RESULTS: Haemodynamically significant PVD was found in 21 (31%) FH patients and in one (3.7%) control subject, predominantly localized in the femoro-popliteal vessels. CAD was present in 30 (44.1%) FH patients and in one (3.7%) control subject. PVD could be demonstrated in 50% of FH patients with CAD [relative risk 3.2 (95% CI 1.4-7.2)] and in 19% as the first manifestation of vascular disease. Males and females were equally affected. Mean arterial blood pressure of FH patients with PVD was higher compared to FH patients without PVD. CONCLUSIONS: Haemodynamically significant PVD appears to be more prevalent in FH patients than is generally assumed, especially in those with CAD. A relation with lipoprotein levels could not be demonstrated.

Adult↗