Biomedical subjects

V Manninen

Publications and source records attributed to V Manninen.

At least 37 records · Page 2Linked to original sources

PubMed1994

Relation between QT intervals and heart rates from 40 to 120 beats/min in rest electrocardiograms of men and a simple method to adjust QT interval values.

OBJECTIVES: The aim of this study was to establish the relation between QT intervals and a wide range of rest heart rates in men. These data provided the basis of a simple method for adjusting the QT interval for heart rate. BACKGROUND: Earlier correction equations give conflicting results, especially at low and high heart rates. METHODS: The QT intervals were measured in 324 electrocardiograms of healthy young men. The sample was weighted for low and high heart rates. A curve relating QT intervals and heart rates from 40 to 120 beats/min was constructed. The QT interval at 60 beats/min was used as the reference value, and an adjusting nomogram for different heart rates was created. The reliabilities of the nomogram and three earlier QT correction equations were tested in the study group and in 396 middle-aged men. RESULTS: The nomogram method presented (QTNc = QT + correcting number) adjusted the QT interval most accurately over the whole range of heart rates on the basis of smallest mean-squared residual values between measured and predicted QT intervals. The Fridericia formula (QTFc = QT/RR1/3) gave the best correction at low, but failed at high, heart rates. The linear regression equation (QTLc = QT + 0.154[1 - RR], Framingham Study) was reliable at normal, but failed at low and high, heart rates. The Bazett formula (QTc = QT/RR1/2) performed poorest at all heart rates. The relation between QT and RR intervals was determined by three linear regressions expressing the slopes 0.116 for heart rates < 60 beats/min, 0.156 for heart rates from 60 to 100 beats/min and 0.384 for heart rates > 100 beats/min. CONCLUSIONS: The QT-RR relation over a wide range of heart rates does not permit the use of one simple adjustment equation. A nomogram providing, for every heart rate, the number of milliseconds that the QT interval must be corrected gives excellent adjustment.

Adolescent↗

PubMed1994

Gemfibrozil treatment is associated with elevated adrenal androgen, androstanediol glucuronide and cortisol levels in dyslipidemic men.

We have investigated the role of steroid hormones as coronary risk factors in the Helsinki Heart Study population of dyslipidemic middle-aged men. We compare here the effects of gemfibrozil and placebo on the serum levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), their metabolite androstanediol glucuronide (3 alpha-AdiolG), androstenedione, cortisol, testosterone, and sex-hormone binding globulin (SHBG) in non-smokers. We also examined the associations between steroid and lipoprotein levels in both treatment groups. Compared with placebo gemfibrozil treatment was associated with significant elevations of the mean levels of DHEA 10.2 vs 8.0 nmol/l; P < 0.005, of DHEAS 8.0 vs 5.8 mumol/l; P < 0.001, of 3 alpha AdiolG 18.3 vs 8.4 nmol/l; P < 0.001, of androstenedione 5.7 vs 5.1 nmol/l; P < 0.02, and of cortisol 426 vs 358 nmol/l; P < 0.001. The mean SHBG levels decreased from 46.4 to 41.7 nmol/l; P = 0.03 with gemfibrozil treatment. No difference was found in testosterone levels 17.7 vs 18.8 nmol/l; P = 0.11, or the ratio of testosterone/SHBG 0.45 vs 0.43; P = 0.23. Positive correlations were found between high density lipoprotein-cholesterol and DHEAS (r = 0.267; P < 0.01) and DHEA (r = 0.282; P < 0.01) levels and negative correlations between low density lipoprotein-cholesterol and 3 alpha-AdiolG (r = -0.400; P < 0.001) and cortisol (r = -0.281; P < 0.01) levels in the gemfibrozil group. Our results indicate that gemfibrozil treatment increases the production and turnover of adrenal androgens and cortisol, and suggest that activation of the adrenocortical function and increased metabolism of androgens are related to the improved lipoprotein pattern during gemfibrozil treatment.

Adrenal Cortex Hormones↗

PubMed1994

Serum ferritin and ceruloplasmin as coronary risk factors.

Iron and copper catalyze lipid peroxidation in vitro, and recent epidemiological data suggest that these metal ions might also be involved in human coronary heart disease. We tested the hypothesis by investigating whether the storage proteins ferritin and ceruloplasmin were coronary risk factors. A nested case-control study was set up in middle-aged dyslipidaemic participants of the Helsinki Heart Study: a placebo-controlled coronary primary prevention trial with gemfibrozil. Of the 140 subjects with cardiac end-points (non-fatal myocardial infarction or cardiac death) 136 were matched with controls for geographical area and drug treatment (gemfibrozil-placebo). Frozen baseline serum samples were used in the analyses of ferritin and ceruloplasmin. Using logistic regression analyses no increment in coronary risk was detected with increasing ferritin levels (P = 0.8 for trend). Ceruloplasmin was higher 349 +/- 86 vs 317 +/- 77 mg.l-1 (P < 0.001) in cases than in controls and the risk in the highest tertile was two-fold (odds ratio 2.1; 95% CI 1.1-4.2) compared to the lowest (P < 0.005 for trend). The risk of high ceruloplasmin was influenced by lipoprotein cholesterol concentrations, with an odds ratio of 2.4 (95% CI 1.3-4.4) in subjects with high low density lipoprotein cholesterol and of 11.3 (95% CI 2.5-52.2) in subjects with low high density lipoprotein cholesterol. It was concluded that ferritin was not associated with coronary heart disease in dyslipidaemic, middle-aged men, while there was a continuous and graded increment in coronary risk with elevating ceruloplasmin level.

Case-Control Studies↗

PubMed1994

The Helsinki Heart Study: an 8.5-year safety and mortality follow-up.

OBJECTIVES: Earlier monitoring of all symptoms, hospital admissions, cancer diagnoses and causes of death during gemfibrozil treatment had raised some suspicions which called for further follow-up. DESIGN: Close monitoring of selected, potentially adverse events amongst treated subjects after a placebo-controlled trial and comparing occurrences to those in various untreated groups. SETTING: All participants of the Helsinki Heart Study (a controlled, 5-year, multi-clinic coronary heart disease (CHD) primary prevention trial with gemfibrozil and placebo) were offered gemfibrozil treatment and twice yearly follow-up for 3.5 years. Untreated groups in the source population and national cancer statistics were utilized in comparisons. SUBJECTS: Of the 2046 dyslipidaemic men initially randomized to gemfibrozil, 2002 survivors entered the 3.5-year follow-up; of the 2035 initial placebo men, 1992 continued to be monitored. INTERVENTIONS: Gemfibrozil was chosen for the follow-up by 66.3% of the gemfibrozil-treated and 68.5% of the placebo-treated men. MAIN OUTCOME MEASURES: Gastrointestinal symptoms, surgery, strokes, cancer incidence, mortality by cause. RESULTS: Gastrointestinal symptoms remained more common in the original gemfibrozil group. After 8.5 years strokes numbered 32 (gemfibrozil) vs. 37 (placebo), violent deaths 16 vs. 14, and cancers 51 in both groups. Total mortality was equal during the original 5 years, but higher in the gemfibrozil group post-trial, leading to an 8.5 year mortality of 101 vs. placebo 83 (P = 0.19). This was mainly a result of higher cancer mortality in the gemfibrozil (30) than the placebo group (18, P = 0.08). An additional 18-month post-study registry follow-up disclosed 13 placebo and five gemfibrozil cancer deaths, altering the cancer mortality to gemfibrozil 35 vs. placebo 31 at 10 years. CONCLUSIONS: The most plausible explanation for the discrepancy between cancer incidence and cancer-specific mortality, based mainly on comparison with untreated groups, is delayed diagnosis. The increased cancer and total mortality is most probably due to chance, based on the later reversal of trends.

Adult↗

PubMed1994

The Helsinki Heart Study: coronary heart disease incidence during an extended follow-up.

OBJECTIVES: To confirm that coronary heart disease (CHD) can be prevented by gemfibrozil treatment and to estimate the long-term effect of the treatment. DESIGN: All participants of the Helsinki Heart Study, a controlled 5-year CHD primary prevention trial with gemfibrozil and placebo, were offered gemfibrozil treatment and biannual follow-up for 3.5 more years. SETTING: By the end of the multi-clinic double-blind trial, a 34% difference in definite cardiac events (56 vs. 84; P < 0.2) had developed between the gemfibrozil and placebo groups. SUBJECTS: There were 2046 dyslipidaemic men in the gemfibrozil group at randomization, 1961 started the extended follow-up; the comparison group comprised 2035 men, and 5 years later 1928 men. INTERVENTIONS: Gemfibrozil was selected by 66.3% of gemfibrozil and 68.5% of placebo men without previous CHD end-points. MAIN OUTCOME MEASURES: Definite fatal and non-fatal CHD events are reported, possible CHD events were recorded but reported selectively. RESULTS: During the post-trial period the numbers of definite CHD events in both groups (54 vs. 47; NS) were smaller than expected without treatment, namely a reduction of around 40% for the original treatment groups. The mean incidence rates were in fact similar to that in the placebo group 5 years earlier. The post-trial CHD incidence was lowest amongst the placebo group men who later selected gemfibrozil. Cardiovascular mortality over the entire study period was similar but all-cause mortality was slightly higher amongst men of the original gemfibrozil group compared to the placebo group men (P = 0.19). CONCLUSIONS: Thus prolonged gemfibrozil treatment postpones cardiac events. This protective effect presumably involves both attenuation of atherosclerosis and mechanisms related to acute cardiac events.

Adult↗

PubMed1994

HDL cholesterol and mortality in Finnish men with special reference to alcohol intake.

BACKGROUND: There is substantial evidence that a low serum level of HDL cholesterol (HDLC) is a risk factor for coronary deaths. However, data on older people are scarce, and previous studies have not examined this association in relation to alcohol intake. METHODS AND RESULTS: Coronary mortality, all-cause mortality, and mortality due to alcohol and violence were related to HDLC levels among 7052 male smokers 50 to 69 years old in south and west Finland enrolled from 1984 to 1988 in the ATBC (AT, alpha-tocopherol; BC, beta-carotene) Study placebo group. During the average follow-up period of 4.7 years, 620 men died; 222 of these deaths were from coronary heart disease and 82 from causes related alcohol and violence. HDLC levels were inversely associated with coronary mortality, irrespective of age, whereas high total cholesterol was positively associated with coronary mortality among the younger men, 50 to 59 years of age, but not among the older men, 60 to 69 years old. Correction for temporal variation in HDLC measurement indicated a 43% stronger inverse association between HDLC and coronary mortality compared with that based only on a single value. The inverse association of HDLC and coronary mortality was less marked at higher levels of alcohol intake. All-cause and alcohol- and violence-related mortality were positively associated with HDLC among the younger men. All-cause mortality showed a U-shaped dose response among men > or = 60 years old. CONCLUSIONS: Previous studies may have underestimated the beneficial effect of high HDLC because of regression-dilution bias and the confounding effect of heavy alcohol intake. This study supports the view that, particularly among older men, lipoprotein fractions may be more appropriate for screening than total cholesterol.

Aged↗

PubMed1993

Enalapril versus atenolol in the treatment of hypertensive smokers.

A randomised crossover study has been done to compare the antihypertensive efficacy of enalapril and atenolol in 45 smoking, hypertensive men. Treatment was started with enalapril 20 mg/d or atenolol 50 mg/d and, if necessary, the doses were doubled after 4 weeks to achieve a sitting diastolic blood pressure < or = 95 mm Hg, after which hydrochlorothiazide was added, if necessary. Both drugs lowered blood pressure significantly. However, enalapril was more efficient in lowering both systolic and diastolic blood pressure; the mean difference was significant after both 4 and 8 weeks in the sitting systolic (11.6 mm Hg and 7.9 mm Hg) and diastolic (3.3 mm Hg and 3.0 mm Hg) pressures and in the erect systolic pressures (8.2 mm Hg and 7.2 mm Hg), and after 8 weeks in the supine systolic pressure, too (8.9 mm Hg). The effect on enalapril was especially marked in moderate (< 20 cigarettes/day) smokers. The need for diuretics was also significantly less in the enalapril group. It appears that angiotensin-converting enzyme inhibitors may be superior to beta-adrenoceptor blockers in the treatment of hypertensive smoking patients.

Aged↗

PubMed1993

Seasonal variation in high density lipoprotein cholesterol.

We investigated the seasonal variation in high density lipoprotein cholesterol (HDL) in 142 dyslipidemic (non-HDL-cholesterol > or = 5.2 mmol/l) middle-aged men in the placebo group of the Helsinki Heart Study over the 5-year trial period. A seasonal pattern was found in HDL fluctuation, with a 4.5% drop during mid-winter (5-year mean 1.192 +/- 0.265 mmol/l) compared with a stable level (5-year mean 1.248 +/- 0.281 mmol/l) during the rest of the year (P < 0.001). A less pronounced seasonal variation in HDL was observed in 85 subjects receiving gemfibrozil. Although affecting pretrial HDL level in cross-sectional analyses, age, alcohol consumption, dietary adherence, physical activity and serum triglycerides had no influence on the seasonality of HDL variation. Smoking had a slight attenuating effect on the variation pattern. Pretrial HDL was influenced by relative weight, but there was also an inverse relationship between HDL and body weight variations, i.e. the annual drop in HDL coincided with the annual peak in body weight. However, seasonal HDL variation was not directly reflected in the annual variation in CHD incidence.

Adult↗

PubMed1993

Cigarette smoking is associated with elevated adrenal androgen response to adrenocorticotropin.

Cigarette smoking alters the pattern of endogenous steroid levels. We examined this phenomenon in two separate male groups. Group A consisted of 189 dyslipidemic men participating in the Helsinki Heart Study and group B of 100 men including patients with heart disease and healthy controls. The subjects in the latter group underwent ACTH-testing. In group A, smokers had significantly higher basal androstenedione and dehydroepiandrosterone sulfate (DHEAS) levels and androstenedione/cortisol ratios than nonsmokers. Mean concentrations of cortisol, dehydroepiandrosterone (DHEA), androstanediol glucuronide, testosterone, and sex-hormone binding globulin (SHBG) did not differ between smokers and nonsmokers. In group B, smokers had lower high density lipoprotein (HDL)-cholesterol and apolipoprotein AI and higher triglyceride levels than nonsmokers. Basal androstenedione and ACTH stimulated androstenedione and DHEA concentrations were higher in smokers. No significant differences were found in basal insulin, SHBG, estrone, estradiol, testosterone, free testosterone, and dihydrotestosterone concentrations between smokers and nonsmokers. These results suggest that smoking decreases the activity of either 21- or 11 beta-hydroxylase in the adrenal cortex, which results in increased secretion of adrenal androgens.

Adrenal Glands↗

PubMed1993

High-density lipoprotein cholesterol elevation with gemfibrozil: effects of baseline level and modifying factors.

The effects of baseline level and modifying factors on gemfibrozil-induced high-density lipoprotein (HDL) cholesterol elevation were studied in 1028 participants with good compliance in the Helsinki Heart Study. The absolute (mmol/L) increment in HDL cholesterol was independent of baseline when the change in the placebo group (regression toward the mean) was considered. In contrast, absolute reductions in low-density lipoprotein (LDL) cholesterol and triglycerides correlated with their baselines, relative percentage changes being constant. Statistically, this could indicate differences in the mode of action of gemfibrozil: an independent and additive effect on HDL cholesterol and a multiplicative effect on LDL cholesterol and triglycerides. These differences may have a physiologic background because the main effect of gemfibrozil is in the stable HDL3 subfraction, rather than in the variable HDL2. Only 13% of the variation in gemfibrozil-induced HDL cholesterol changes were explained by modifying factors. The basic assumptions in the uses of absolute or relative changes as a measure of treatment effect are discussed.

Adult↗

PubMed1993

High calcium diet, different antihypertensive agents, and cytosolic free Ca2+ in spontaneously hypertensive rats.

Several studies have shown that increased dietary calcium decreases blood pressure (BP) in spontaneously hypertensive rats (SHR), but the underlying mechanisms are not fully understood. We compared the effects of a high calcium diet and different antihypertensive agents on BP and intracellular free Ca2+ concentration ([Ca2+]i) in lymphocytes of adult SHR. The calcium content of the normal chow was 1.1% and that of the high calcium chow was 2.5%. Antihypertensive drug treatments were performed by giving the animals trichlormethiazide (2 mg/kg/day), atenolol (25 mg/kg/day), and quinapril (10 mg/kg/day) in drinking water. Untreated SHR and normotensive Wistar-Kyoto (WKY) rats served as controls. After 14 weeks of study systolic BP (SBP) and [Ca2+]i in blood lymphocytes, measured with a fluorescent indicator quin-2, were higher in untreated SHR than in WKY rats. Trichlormethiazide, atenolol, quinapril, and the high calcium diet all decreased BP in SHR, but only quinapril and calcium-rich diet concurrently reduced [Ca2+]i. We conclude that the reduction in [Ca2+]i during high calcium intake does not result from decreased BP itself. If the changes in lymphocyte [Ca2+]i reflect Ca2+ metabolism in other tissues as well, especially in vascular smooth muscle, the normalization of [Ca2+]i may be involved in the BP-lowering mechanisms of oral calcium loading and angiotensin-converting enzyme (ACE) inhibition in genetic hypertension.

Animals↗

PubMed1993

Severity of peripheral atherosclerosis is associated with fibrinogen and degradation of cross-linked fibrin.

Immunohistochemical studies of human atherosclerotic lesions have demonstrated the occurrence of fibrin deposition and its degradation in the arterial wall. We studied fibrinogen, the generation of thrombin, and the degradation of fibrin in 40 patients with stable peripheral arterial occlusive disease of varying severity, as assessed by the ankle/brachial pressure index and duplex ultrasonography and/or angiography. Circulating fibrinogen (functional and immunological), fibrinopeptide A, thrombin-antithrombin III complex, and D-dimer were measured. The severity of atherosclerosis was associated with both fibrinogen (both functional and immunological) and D-dimer (r = .57, P < .0002, and r = .57, P < .0001, respectively). Fibrinogen and D-dimer showed a significant positive correlation (r = .50, P < .001). Generation of thrombin was detected in 24 patients (60%) by fibrinopeptide A and levels of thrombin-antithrombin III complex. As a sign of coagulation activation and fibrinolysis, we found that thrombin-antithrombin III complex and the degradation of cross-linked fibrin were progressively associated with the extent of vascular disease. The plasmin-mediated fibrin breakdown contributed to increased levels of circulating fibrinogen, an established risk factor for thrombotic complications. The significant correlations between fibrinogen/D-dimer and the severity of atherosclerosis support previous pathological studies and imply that local degradation of cross-linked fibrin is involved in the progression of atherosclerosis.

Adult↗

PubMed1993

Efficacy of gemfibrozil in dyslipidaemic subjects with suspected heart disease. An ancillary study in the Helsinki Heart Study frame population.

During screening in the Helsinki Heart Study (HHS), a 5-year coronary primary prevention trial with gemfibrozil, some 600 dyslipidaemic individuals were detected who exhibited symptoms and signs of possible coronary heart disease (CHD). These subjects were excluded from the primary study. To secure successful conduct in the HSS, an ancillary protocol was developed for the treatment of these individuals. Three-hundred and eleven subjects were randomized to receive gemfibrozil 600 mg twice daily and 317 subjects to receive a matching placebo over 5 years in a double-blind fashion. The end-point rate, consisting of fatal and non-fatal myocardial infarction and cardiac death, did not differ significantly between the placebo and gemfibrozil groups. The same was true for total mortality. Missing key prognostic factors, e.g. true prevalence of CHD, extent of coronary artery obstructions, degree of left ventricular dysfunction, and their distribution in the groups render the results less reliable and hence the data cannot be used to refute the thesis that treatment of dyslipidaemia in manifest CHD in successful.

Adult↗

PubMed1992

Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study.

OBJECTIVE: To investigate in the prospective Helsinki Heart Study, whether chronic Chlamydia pneumoniae infection, indicated by elevated antibody titers against the pathogen, chlamydial lipopolysaccharide-containing immune complexes, or both, is a risk factor for coronary heart disease. DESIGN AND SETTING: The Helsinki Heart Study was a randomized, double-blind, 5-year clinical trial to test the efficacy of gemfibrozil in reducing the risk for coronary heart disease. Participants were randomized to receive either gemfibrozil (2046 patients) or placebo (2035 patients). Fatal and nonfatal myocardial infarction and sudden cardiac death were the main study end points. Serum samples were collected at 3-month intervals from all patients. PATIENTS: One hundred forty cardiac events occurred during the follow-up period. Serum samples from 103 case patients obtained 3 to 6 months before a cardiac end point were matched with those from controls for time point, locality, and treatment. Samples were tested for markers of chronic chlamydial infection. MEASUREMENTS: Immunoglobulin A (IgA) and G (IgG) antibodies to C. pneumoniae were measured using the microimmunofluorescence method. Lipopolysaccharide-containing immune complexes were measured using two antigen-specific enzyme immunoassays, the lipopolysaccharide-capture and immunoglobulin M (IgM)-capture methods. MAIN RESULTS: Using a conditional logistic regression model, odds ratios for the development of coronary heart disease were 2.7 (95% CI, 1.1 to 6.5) for elevated IgA titers, 2.1 (CI, 1.1 to 3.9) for the presence of immune complexes, and 2.9 (CI, 1.5 to 5.4) for the presence of both factors. If we adjusted for other coronary heart disease risk factors such as age, hypertension, and smoking, the corresponding values would be 2.3 (CI, 0.9 to 6.2), 1.8 (CI, 0.9 to 3.6), and 2.6 (CI, 1.3 to 5.2), respectively. CONCLUSION: The results suggest that chronic C. pneumoniae infection may be a significant risk factor for the development of coronary heart disease.

Adult↗

PubMed1992

A novel polymorphism of apolipoprotein A-IV is the result of an asparagine to serine substitution at residue 127.

We have identified a hitherto unknown genetic polymorphism of apolipoprotein A-IV (apoA-IV). The molecular basis for this polymorphism is an A to G substitution at nucleotide 1687 resulting in an Asn to Ser change of amino acid 127. The frequencies of the two apoA-IV alleles (designated apoA-IV127Asn and apoA-IV127Ser), determined by Hin c II restriction analysis of PCR amplified exon three of the apoA-IV gene, were 0.788 and 0.212, respectively, in a Finnish population sample. Allele frequencies of another polymorphism due to a Thr to Ser substitution at amino acid 347 were determined using Hinf I restriction analysis. The allele frequencies were 0.823 for apoA-IV347Thr and 0.177 for apoA-IV347Ser. None of the apoA-IV polymorphisms (apoA-IV127:Asn----Ser, apoA-IV347:Thr----Ser and apoA-IV360:Gln----His) had any effect on plasma lipid and lipoprotein concentrations in cohorts of dyslipidemic men and in a population sample of normolipidemic controls. There was also no association between the history of previous myocardial infarction and any of the apoA-IV alleles.

Alleles↗

PubMed1992

Anion-dependent transport of thallous ions through human erythrocyte membrane.

Undirectional fluxes of 204Tl+ through the human red blood cell membrane were measured. The inward rate coefficient measured in a K(+)-free saline was 15.6 +/- 0.6 hr-1. The influx of Tl+ could be partially inhibited with 0.1 mM ouabain (by 28%), 0.1 mM DIDS (by 50%) or 1 mM furosemide (by 51%). The inhibitory effects of ouabain and DIDS or furosemide were additive. Half-maximal responses were seen at 0.72 microM and 0.22 mM concentrations of DIDS and furosemide, respectively. A similar action of these blockers on Tl+ influx was observed in the erythrocytes incubated in MgCl2-sucrose media. The outward rate coefficient of 204Tl was also inhibited by DIDS and furosemide (by 65 and 52%, respectively). Rate coefficients of 204Tl influx and efflux decreased significantly in the red cells exposed to Cl(-)-free media (NaNO3 or Mg(NO3)2-sucrose). Under these conditions addition of DIDS and furosemide led to only a small inhibition of Tl+ fluxes. There was a linear increase in Tl+ influx with rising of external Cl- concentration within 80-155 mM or HCO3- concentration from 20 to 40 mM when the sum of anions was kept constant (155 mM) with NO3-. The HCO3(-)-stimulated Tl+ influx was completely blocked by 0.05 mM DIDS but only 67% by 1 mM furosemide. The present study provides direct evidence for the occurrence of Cl- (HCO3-)-dependent, DIDS-sensitive movement of Tl+ across the human erythrocyte membrane in both directions. Under physiological conditions, about half of net Tl+ fluxes occurs due to an anion exchange mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1992

Compliance with medication in the Helsinki Heart Study.

Compliance with medication has a decisive influence on the findings in clinical intervention studies, so the reliable estimation of compliance is vital to the success of such research. This report describes the main findings about compliance in the Helsinki Heart Study, a five-year, double-blind, primary prevention trial of gemfibrozil as a lipid-lowering agent compared with placebo, in 4,081 dyslipidaemic middle-aged men. Three estimation methods were employed: capsule counting at every three-month follow-up visit, urine gemfibrozil analysis at six-month intervals, and, a novel technique, a digoxin marker added to both gemfibrozil and placebo capsules at the end of the third and fifth study years. The estimates of compliance for the study population as a whole generated by these three methods are discussed here. The mean daily capsule count showed that 36% of patients on gemfibrozil men and 39% of those on placebo took more than 90% of their capsules, while only 5% of both groups consumed half or less of the prescribed treatment. According to urinary gemfibrozil analysis, 30% of gemfibrozil subjects had more than 90% positive results and 28% had half or fewer positive. Among study completers, there were 42% gemfibrozil subjects and 50% placebo subjects who on both occasions had the good result in the digoxin marker analysis, while 14% of the gemfibrozil men and 12% of the placebo men scored 'poor' in both marker analyses. Capsule counting revealed a slight deterioration in compliance over the trial period, which was confirmed by the other two methods; for example, the proportion of positive results in the semiannual urine gemfibrozil analyses decreased from 76% to 65%. Medication compliance was slightly better in the placebo group according to capsule counting and digoxin marker methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Capsules↗

PubMed1992

Leukocytes as a coronary risk factor in a dyslipidemic male population.

The role of an elevated serum leukocyte count (WBC) as a coronary risk factor was investigated using a nested case-control design in dyslipidemic middle-aged men (n = 420) participating in the Helsinki Heart Study, a coronary primary prevention trial. Baseline WBC was significantly higher, 6.93 (2.11) x 10(9)/L in subjects with cardiac events, than in controls, 6.26 (1.88) x 10(9)/L; p less than 0.002. This association was time-dependent, however, since the difference was not significant for events occurring during the second half of the 5-year study. Using nonsmokers in the lowest WBC tertile as the reference sample, the relative risks in the highest WBC tertile were 1.86 (95% confidence intervals [CI] 0.81 to 4.28) for nonsmokers and 3.07 (95% CI 2.23 to 8.19) for smokers. Logistic regression analysis including smoking in the model disclosed an independent contribution of elevated WBC to coronary heart disease. We conclude that elevated leukocyte count was a coronary risk factor even in this dyslipidemic population.

Case-Control Studies↗