Biomedical subjects
Publications and source records attributed to I Hjermann.
We have analyzed the correlation between restriction site variants (RFLPs; restriction fragment length polymorphisms) of the apolipoprotein AI, AII, B, CI and CII genes and serum lipid levels in a sample of male Norwegians. We find no significant association between any of the RFLPs and lipid levels.
We propose practical dietary advice for patients with hyperlipidemias, based on data obtained from new results in epidemiology, clinical trials and laboratory experiments. We suggest a schedule for obtaining reliable data on dietary habits, to be used as a basis for advice to the individual patient. If the dietary fat intake can be reduced from about 40% to 25% of the total energy it is possible to achieve an average reduction in serum cholesterol of 10-20%. It is very important that doctors and other health personnel become involved in providing dietary advice in connection with treatment and prevention of coronary heart disease.
The article summarizes the use of laboratory analysis as described in the recently published Norwegian program for diagnosis and treatment of hypercholesterolemia in adults. Serum cholesterol is used both to diagnose hypercholesterolemia and to monitor the effect of treatment. Serum triglycerides should be measured when hypercholesterolemia has been found and dietetic treatment is considered. High density lipoprotein (HDL) cholesterol should be measured when dietetic treatment has not reduced hypercholesterolemia sufficiently and drug treatment is considered. We do not at present recommend measurement of apolipoproteins and factors within coagulation/fibrinolysis, but such measurements might be of importance in the near future. Blood cholesterol exhibits large biological variations, which makes retesting necessary before hypercholesterolemia is diagnosed. Analytical variation is usually less than biological variation, but requires use of quality control materials. This control is equally important for small dry chemistry analyzers as for wet chemistry analyzers.
To examine the effect of dopamine on in vivo platelet function and a possible platelet contribution to the clearance of dopamine we measured platelet count, platelet size and plasma concentration of the platelet specific protein beta-thromboglobulin (BTG) in groups of 40 year old untreated hypertensive and normotensive men. One hypertensive (n = 10) and one normotensive (n = 10) group received dopamine infusion at doses from 0.5 to 2.0 micrograms/kg/min which increased plasma dopamine 100-fold from baseline. Two other groups of hypertensive (n = 10) and normotensive (n = 11) subjects received 10 mg of the dopamine antagonist metoclopramide intravenously, upon which serum prolactin concentration increased 10-fold. No significant effect on platelet function in any group was observed during these interventions. Platelet phenol-sulphotransferase may contribute to dopamine conjugation. However, the selected platelet parameters correlated only weakly with dopamine kinetics during the infusion. Neither dopamine nor a dopamine antagonist altered the selected platelet parameters, nor did these parameters influence the clearance of dopamine during a short-lasting pharmacological infusion.
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We have studied the effect of lovastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase), alone and in combination with the bile acid sequestrant cholestyramine on lipid parameters in 30 heterozygous patients with familial hypercholesterolemia (FH) during a 20-week open trial. Lovastatin 40 mg bid (twice daily) decreased significantly total serum cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides and apolipoprotein B by 36%, 45%, 29% and 11%, respectively, while high density lipoprotein (HDL)-cholesterol and apolipoprotein A-I were increased significantly by 16% and 37%, respectively. These data are consistent with a reduction in both the number of LDL particles and in their cholesterol content. Addition of cholestyramine 4 g bid caused a significant further decrease in total serum cholesterol and LDL-cholesterol to a total of 43% and 61%, respectively. The addition of 4 g bid or 8 g bid of cholestyramine caused only minor changes in the other lipid parameters. No effect was found by these drugs on Lp(a) lipoprotein level. We conclude that lovastatin alone or in combination with a small dose of cholestyramine normalizes the lipid profile in most FH heterozygotes.
Forty-year old men with untreated mild essential hypertension (n = 35) had decreased serum phosphate (P less than 0.001) concomitant with elevated resting plasma epinephrine (P less than 0.05) and heart rate (P less than 0.001) compared with age-matched, normotensive control men (n = 44). Blood pressure correlated negatively with serum phosphate (P less than 0.001) and positively with plasma epinephrine (P less than 0.01) and heart rate (P less than 0.01). Serum phosphate was significantly lowered during infusion of epinephrine, increasing arterial plasma epinephrine within the lower pathophysiological range corresponding to arousal reactions. Serum concentrations of immunoreactive parathyroid hormone were unchanged. Thus, hypophosphatemia in patients with mild essential hypertension appears to be inversely related to sympathetic adrenal tone and may be caused by increased plasma epinephrine within pathophysiologic arterial concentrations.
The never-treated control group in the Oslo Study hypertension trial of middle-aged men 40-49 years old at entry (n = 379) was studied with respect to five-year change in blood pressure and its correlates. The study began in 1972 and ended in 1979, and each patient was followed for five years. Both baseline and rate of change of correlates were analyzed as independent variables versus rate of change in blood pressure as the dependent variable. Rate of change in serum triglycerides were found to be the strongest correlate of rate of change in blood pressure in this population of healthy mild hypertensives. In addition, rate of change in serum cholesterol and body weight made significant contributions in some analyses, but to a lower degree than did rate of change in triglycerides. The model predicts a substantial decrease in blood pressure if lipids and body weight are reduced. Rate of change in sodium, uric acid, and chloride concentrations were also associated with blood pressure change, but total degree of explanation of all explaining variables only accounted for 11-15% of total variation in annual blood pressure change.
During low-dose adrenaline infusion, platelet count, platelet size, plasma beta-thromboglobulin (BTG) and forearm vascular resistance (FVR) were measured in twelve 40-year-old men with mild, untreated hypertension. The average platelet count increased from 195 to 226 X 10(9)/l (P less than 0.001), platelet size from 7.31 to 7.53 X 10(-15)/l (P less than 0.01), BTG from 0.61 to 1.08 nmol/l (P less than 0.02) and FVR decreased from 97 to 58 (arbitrary units; P less than 0.001) during the infusion. The change in platelet count reflects splenic release of platelets, the change in plasma BTG reflects platelet release reaction, while the reduced FVR reflects vascular smooth muscle cell relaxation. In 11 normotensive men aged 40 years, platelet count increased from 187 to 201 X 10 g/l (P less than 0.01) during an equal low-dose adrenaline infusion. This increase in platelet count is significantly less than in the hypertensive group (P less than 0.01). There was statistically no significant change in platelet size, BTG or FVR in the normotensive group. Arterial adrenaline rose from 0.5 to 2.5 nmol/l in the hypertensive and from 0.5 to 2.4 nmol/l in the normotensive group. A third group of 12 normotensive men received saline infusion: neither platelet parameters nor FVR changed in this group. Thus, a small and equal dose of adrenaline elicited a greater increase in platelet count, an enhanced platelet release reaction and a more pronounced forearm vasodilation in hypertensive than in normotensive subjects.
The present study was undertaken to evaluate the effects of intravenous infusion of small amounts of epinephrine on haemodynamics, renal electrolyte excretion and blood platelets in essential hypertension. Arterial plasma epinephrine concentrations were increased during the infusion to approximately 2.5 nmol/l both in a group of 40-year-old men with untreated mild essential hypertension (blood pressure 154 +/- 3/100 +/- 3 mmHg, n = 12) and in a group of age-matched male controls (124 +/- 3/78 +/- 2 mmHg, n = 11). In the hypertensive group only, mean blood pressure decreased, forearm blood flow increased, forearm vascular resistance decreased (P less than 0.001 for all) and the urinary excretion of sodium and potassium increased (P less than 0.01 for both). The hypertensive group also responded with an increase in plasma beta-thromboglobulin (P less than 0.05), blood platelet size (P less than 0.05) and a higher increase in platelet counts than in the normotensive group (P less than 0.05). Thus, in several ways the hypertensive patients showed a hyper-responsiveness to amounts of epinephrine which corresponds well to the plasma concentration achieved during psychological and physical activity.
Twenty healthy individuals (15 men and 5 women) with initial fasting serum triglycerides greater than or equal to 1.80 mmol/l and euglobulin clot lysis time after venous occlusion greater than or equal to 60 min (upper normal limit 45 min) were tested for fibrinolytic response to venous occlusion and intravenous injection of desmopressin (DDAVP), serum lipids, serum glucose and relative body weight before and after a minimum of 3 to a maximum of 12 months' diet intervention. In order to be defined as a good diet responder, at least 20% reduction of the initial serum triglyceride concentration was required. At the end of the study, half of the participants (7 men and 3 women) met the criteria of good diet responders. All of these showed an improved fibrinolytic response to DDAVP injection, and 7 out of 10 had a normalized fibrinolytic response to venous occlusion. We conclude that, through dietary measures with substantial reduction of hypertriglyceridaemia, it is possible to improve and even normalize the fibrinolytic potential.
Subjects with non-familial hypercholesterolemia who were homozygous for absence of an XbaI restriction site in the apolipoprotein B gene (genotype X2X2) had significantly lower values of apolipoprotein B than those possessing the site. Our data are in agreement with those of Berg (1986) and Law et al. (1986) indicating that X2X2 homozygotes have lower levels of apolipoprotein B, total serum cholesterol, triglycerides and LDL cholesterol. The mechanism underlying this effect is unknown, but could reflect different LDL metabolism between subjects with different genotypes.
One of the 2 controlled preventive trials within the Oslo Study was a non-drug trial on the effect of diet and smoking intervention on coronary heart disease in 1232 middleaged, normotensive, healthy men. All had elevated serum cholesterol and 4 out of 5 smoked every day. The participants in the intervention group met every 6 months during the 5-year study for clinical examination and for dietary and smoking counselling. The effect on serum cholesterol was a 13% lowering (i.e. 10% net reduction compared with control group), and about a 50% reduction in cigarette consumption. The effect on coronary heart disease (fatal and non-fatal myocardial infarction or sudden death) was a 47% lowering of the 5-year incidence in the intervention group compared with the control group (p = 0.02, 2-sided). The main intervention strategies were: information about the risk factor concept to participant and spouse (in groups) individual diet and anti-smoking counselling after finishing an extensive clinical and electrocardiographic examination, including exercise-ECG basis and background for the counselling strategy: the total situation of the participant. Some of the most important items: personality, motivation, diet history, bodyweight, blood lipids and blood sugar anti-smoking advice given individually to all smokers in the intervention group advice that smoking cessation was expected to be of special importance for those with elevated blood lipids.
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Baseline serum prolactin (PRL) was found to be similar in 35 men with untreated essential hypertension (149 +/- 2/98 +/- 1 mmHg; means +/- s.e.) and 44 healthy normotensive men (126 +/- 1/80 +/- 1 mmHg), all 40 years old. A correlation between baseline PRL and aldosterone was found in the normotensive (r = 0.534, P less than 0.001), but not in the hypertensive group (r = -0.011, NS). Ten subjects from each group received intravenous metoclopramide, a competitive dopamine antagonist, while another 12 normotensive subjects were given saline only, and the effect on PRL, vasopressin (AVP) and catecholamines was followed. An exaggerated PRL response to metoclopramide was observed in the hypertensive group compared with the normotensive (P less than 0.05), and the mean normotensive peak value never exceeded the hypertensive. Plasma noradrenaline increased significantly compared with baseline (P less than 0.05) and the control group (P less than 0.001), concomitant with increased heart rate (P less than 0.05), after the administration of metoclopramide both in the hypertensive and normotensive group. After intravenous injection of metoclopramide, forearm blood flow increased significantly by 50% in the hypertensive (P less than 0.001), and 80% in the normotensive group (P less than 0.001) compared with the control group. Mean blood pressure remained unchanged as did plasma AVP, dopamine and adrenaline. The present study indicates an altered central dopaminergic activity in essential hypertension. Even at rest, endogenous dopamine exerts a modulating effect on noradrenaline release in both hypertensive and normotensive men.