Elevated plasma fibrinogen caused by inadequate alpha-linolenic acid intake can be reduced by replacing fat with canola-type rapeseed oil.

The effects of canola-type rapeseed oil (RSO) on serum lipids, plasma fibrinogen, lipid oxidation and fatty acids were studied in three groups of subjects, two of which had not been consuming fish in their habitual diets. Forty-two volunteers (35 women, 7 men, 16-62 years) replaced fat with RSO for 6 weeks in a parallel design. The average cholesterol and fibrinogen concentrations were 5.0 mmol/l and 2.6 g/l, respectively. The intake of alpha-linolenic acid (alpha-LLA) was doubled. Efficient competitive inhibition by alpha-LLA was seen as a decrease in long-chain (LC) n-6 PUFA at 3 weeks. Elevated fibrinogen (2.6-3.9 g/l) decreased by 0.95 g/l at 6 weeks. Docosahexaenoic acid (22:6n-3) in plasma phospholipids increased at low fibrinogen levels only. The associations and changes in plasma C18 and LC PUFA followed the competitive and metabolic principles of the body, and especially in the case of n-3 PUFA according to the recycling pathway.

Effects of vitamin E on the toxicity of oxidized LDL on endothelial cells in vitro in smokers vs nonsmokers on diets rich in fish.

OBJECTIVE: To clarify whether supplementation of vitamin E can alter the low density lipoprotein (LDL) oxidation properties and thereby affect endothelial cell function and prostacyclin production in smokers compared to nonsmokers on diets rich in fish in a pilot study. DESIGN: The LDL of six smokers and six nonsmokers on habitual high fish diet was isolated before and after an 8-week supplementation of vitamin E (800 IU/day). LDL was oxidized by incubation with CuSO4. Cytotoxicity of LDL oxidized to different degrees on endothelial cells was investigated in vitro in these two groups. SETTING: Helsinki University Central Hospital; Institute of Biomedicine, Pharmacology, University of Helsinki. RESULTS: At baseline, the rate of oxidation was higher in nonsmokers than in smokers. The lag phase increased significantly after the supplementation of vitamin E both in smokers and nonsmokers. Native LDL dose dependently tended to reduce the viability of endothelial cells in vitro more markedly when isolated from smokers than from nonsmokers. Vitamin E supplementation had no beneficial effect on the cytotoxicity of oxidized LDLs in endothelial cell culture. On the other hand, simultaneous administration of Trolox, the water-soluble analogue of vitamin E, attenuated the LDL cytotoxicity on endothelial cells. The vitamin E supplementation to LDL donors attenuated the increase in prostacyclin production both in smokers and nonsmokers. CONCLUSION: Supplementation of LDL donors (healthy male volunteers on habitual fish diet) with vitamin E increased the lag phase of LDL oxidation, but, on the other hand, did not influence in vitro cytotoxicity of LDL, or prostacyclin production.

Birth outcome in relation to licorice consumption during pregnancy.

A role for glucocorticoids is suspected in the etiology of low birth weight. The authors tested whether maternal consumption of glycyrrhizin (an inhibitor of cortisol metabolism) in licorice affects birth weight in humans. A sample of 1,049 Finnish women and their healthy singleton infants was studied in 1998. Glycyrrhizin intake was calculated from detailed questionnaires on licorice consumption. Glycyrrhizin exposure was grouped into three levels: low (<250 mg/week; n = 751), moderate (250-499 mg/week; n = 145), and heavy (> or =500 mg/week; n = 110). Birth weight and gestational age (from ultrasound measurements) were obtained from hospital records. Babies with heavy exposure to glycyrrhizin were not significantly lighter at birth, but they were significantly more likely to be born earlier: The odds ratio for being born before 38 weeks' gestation was 2.5 (95% confidence interval: 1.1, 5.5; p = 0.03). Although the effect of heavy glycyrrhizin intake on mean duration of gestation was small (2.52 days) when expressed as an effect on the mean, this shift to the left of the distribution of duration of gestation was sufficient to double the risk of being born before 38 weeks. The association remained in multivariate analyses. In conclusion, heavy glycyrrhizin exposure during pregnancy did not significantly affect birth weight or maternal blood pressure, but it was significantly associated with lower gestational age.

Major human plasma lipid classes determined by quantitative high-performance liquid chromatography, their variation and associations with phospholipid fatty acids.

An HPLC method with evaporative light-scattering detection (ELSD) was optimized and validated for the simultaneous quantitation of cholesteryl esters (CEs), triacylglycerols (TGs), free cholesterol (FC) and phosphatidylcholine (PC) in human plasma. The separation of CEs from TGs, the most variable plasma lipid class, was improved by speeding up the gradient steps and by increasing the re-equilibration time between runs. The calibrations were made at levels of 0.14-14 microg lipid/injection. The intra- and inter-day precision values of the method ranged between 1.9 and 4.5 and 2.3-7.2% (RSD, n=6), respectively, including determinations at two concentration levels. In comparison to other lipid classes, quantitation of PC proved to be equally repeatable despite its lowest detector response. The relative recoveries varied from 97.0 to 110.3%, showing good accuracy of the method. The methodological variation of the lipid classes covered 0.6-3.1% of their total variation in the study population (n=48). The CE/FC ratio showed an even closer relationship with phospholipid linoleic acid (18:2n-6; r=0.65, P<0.001) than with serum cholesterol levels, while eicosapentaenoic acid (20:5n-3) was significantly associated with PC (r=0.41, P<0.01). The CE/FC ratio increased (P<0.01) during soyabean oil substitution and the level of PC increased (P<0.01) during cold-pressed rapeseed oil substitution.

Blood pressure and mortality during an up to 32-year follow-up.

BACKGROUND: Elevated blood pressure is an established risk factor of cardiovascular diseases, but there is a constant debate whether the association is continuous or with a threshold. METHODS: During the 1960s (1964 onwards), 3,267 initially healthy male business executives (born 1919-1934) participated in voluntary health check-ups with measurements of cardiovascular disease risk factors. At baseline none of the men were on antihypertensive medication. Mortality follow-up was performed using national registers up to 31 December, 1995. Follow-up total and cardiovascular mortality was related to systolic (by 10 mmHg) and diastolic (by 5 mmHg, Korotkoff's 4th phase) blood pressure at baseline. Analyses were adjusted for age, body mass index, smoking and serum cholesterol. RESULTS: During an up to 32-year follow-up, there were 701 deaths, 234 (33.4%) of them due to coronary heart disease, 49 (7.0%) to stroke, 42 (6.0%) to other cardiovascular diseases and 204 (29.1%) to cancer. Total mortality curves of the whole cohort (all age groups) were flat until 131-140 mmHg (systolic) and 81-85 (diastolic) and increased thereafter. Among men who smoked and had baseline serum cholesterol > 6.5 mmol/l (n = 986), the risk of death increased progressively with systolic blood pressure, whereas among non-smoking normocholesterolaemic men (n = 504) the association was J-shaped, i.e. higher mortality at < or = 110 mmHg than between 111-150 mmHg and a more consistent rise from 151-160 mmHg. The curves were essentially similar for cardiovascular mortality. The results were supported by analyses where major cardiovascular risk factors were controlled. CONCLUSION: During a truly long-term follow-up, the relationship between systolic blood pressure and mortality was initially flat up to 131-140 mmHg although a linear relationship is suggested in men with other cardiovascular risk factors.

Associations between change in C-reactive protein and serum lipids during statin treatment.

Hypolipidaemic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) treatment reduces cardiovascular risk and is also associated with the reduction of C-reactive protein (CRP) concentrations. However, there is scant data concerning the relationship between CRP and lipid changes during statin treatment. We studied 60 hypercholesterolaemic coronary patients who participated in the Treat to Target (3T) study comparing atorvastatin and simvastatin. Serum lipids and CRP (with a sensitive method) were measured before treatment at baseline and after 12 months of statin treatment. Low-density lipoprotein (LDL) cholesterol was substantially decreased and high-density lipoprotein (HDL) cholesterol increased during statin treatment. CRP decreased significantly (sign test P = 0.03) during treatment, and the changes of CRP were significantly associated with changes in HDL cholesterol (r = -0.45; P < 0.001) and apolipoprotein A1 (r = -0.40; P < 0.001) but not with changes in LDL cholesterol or triglycerides. The change in HDL cholesterol explained 20% of the change in CRP during statin treatment. The results are in line with previous suggestions that HDL has anti-inflammatory properties.

Dietary fatty acid composition influences the degree of human LDL oxidation, but has only minor effects on vascular tone in a bioassay system.

BACKGROUND AND AIM: Oxidized LDL has been detected in atherosclerotic vessels and presumed to be one of the major risk factors in atherosclerosis and cardiovascular diseases. The aims of the present study were to clarify whether the oxidation degree of LDL influences arterial tone and whether different long-lasting dietary habits have effects on biological variables. METHODS AND RESULTS: The lag phase of LDL oxidation was shorter (117 +/- 6 min) in the fish diet group than in the vegetarian (153 +/- 5 min) or the control diet group (152 +/- 10 min). The rat mesenteric arterial rings, which were preincubated with LDL oxidized to 1-30%, from the vegetarian and the fish diet groups showed (p < 0.05) decreased NA-induced maximal contraction forces when compared to the control diet. The LDL oxidation degrees of 31-60% and 61-90% had no effect on NA- and KCl-induced maximal contraction forces when compared to native LDL, nor were there differences between the diet groups. Endothelium-dependent and independent relaxation responses behaved similarly in all groups and were independent of the degree of oxidation. CONCLUSIONS: Dietary habits change the fatty acid composition of LDL, but have only minor effects on the vasoactive properties of oxidized LDL.

Response to antihypertensive therapy in older patients with sustained and nonsustained systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

BACKGROUND: The goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension. METHODS AND RESULTS: Patients who were >/=60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (<140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (>/=160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages (P<0.001) and, during follow-up, a lower incidence of stroke (P<0.05) and of cardiovascular complications (P=0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension (P<0.001). The influence of active treatment on ECG voltages (P<0.05) and on the incidence of stroke (P<0.05) and cardiovascular events (P=0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension. CONCLUSIONS: Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.

Excess mortality associated with increased pulse pressure among middle-aged men and women is explained by high systolic blood pressure.

OBJECTIVE: To assess the risk of death from coronary heart disease, stroke, all cardiovascular diseases and all-cause mortality associated with pulse pressure among the middle-aged population. METHODS AND DESIGN: A prospective 15-year follow-up cohort study was conducted of two independent cross-sectional random samples of the population who participated in baseline surveys in 1972 or 1977. Each survey included a self-administered questionnaire with questions on smoking and antihypertensive drug treatment, measurements of height, weight and blood pressure and the determination of the serum cholesterol concentration. Multivariate analyses were performed by using Cox proportional hazard models. SETTING: The provinces of North Karelia and Kuopio in eastern Finland PARTICIPANTS: Men and women aged 45-64 years with no history of myocardial infarction or stroke at the time of the baseline survey were selected. In total 4333 men and 5270 women took part in this follow-up study. RESULTS: The relative risk of coronary heart disease, stroke, cardiovascular disease and all-cause mortality increased with the increasing pulse pressure in individuals aged 45-64 years independent of the diastolic blood pressure level. Only in women with diastolic blood pressure > or = 95 mmHg was the relative risk of fatal stroke not statistically significant. After adjustment for systolic blood pressure, the positive association between mortality and increasing pulse pressure disappeared. CONCLUSION: Increasing pulse pressure is a predictor of death from coronary heart disease, stroke, cardiovascular disease and all causes in men and women aged 45-64 years, but the increase in risk is entirely associated with the increase in systolic blood pressure.

Oxidized LDL from subjects with different dietary habits modifies atherogenic processes in endothelial and smooth muscle cells.

Low-density lipoprotein (LDL) activates a number of processes involved in atherogenesis and vasoconstriction. Evidence suggests that oxidation increases the atherogenicity of LDL. We investigated the effects of oxidized LDL (ox-LDL) on cytotoxicity, prostacyclin (PGI2), and cyclic guanosine-3',5'-monophosphate (cGMP) production in rat vascular smooth muscle cell (VSMC) and rat heart endothelial cell (EC) culture, as well as EC- and VSMC-mediated LDL oxidation. Native LDL (n-LDL) was isolated from subjects on three long-term diets with differing fatty acid content (control diet rich in saturated fat and vegetarian and fish diets). The Cu2+-catalyzed oxidation of n-LDL was monitored using conjugated diene formation and stopped at various time points to achieve 20%, 45%, 70%, and 100% levels of ox-LDL. The lag phase of oxidation by Cu2+ was shortest and thiobarbituric acid-reactive substance (TBARS) formation by VSMC-mediated oxidation was highest with n-LDL obtained from the fish diet group. There were no differences between the ox-LDLs obtained from the different diet groups in their cytotoxicity in EC culture. The degree of oxidation did not influence LDL cytotoxicity. In VSMC culture PGI2 production was increased by ox-LDLs from all diet groups. In EC culture only the extensively oxidized LDLs obtained from the vegetarian diet group were able to induce PGI2 production. The LDLs did not affect basal cGMP production in either EC or VSMC culture.

Frequency of lipid-lowering therapy after a coronary event in Helsinki, Finland.

The results from a survey in Finland suggest an important treatment gap of lipid-lowering medications. Patients whose coronary artery disease was diagnosed before 1995 were less likely to be on lipid therapy than patients with a more recent diagnosis.

Ursodeoxycholic acid and endothelial-dependent, nitric oxide-independent vasodilatation of forearm resistance arteries in patients with coronary heart disease.

AIMS: Ursodeoxycholic acid (UDCA) has cholesterol lowering and anti-inflammatory effects and bile acids are reported to exert vasodilator effects; all of these properties might be considered desirable in a drug used in the treatment of patients with coronary heart disease. We investigated a hypothesis that UDCA may dilate arteries and the mechanism of action. METHODS: We evaluated effects of a 6-week treatment with UDCA in 11 coronary heart disease patients on endothelium-dependent (acetylcholine-induced) and -independent (nitroprusside-induced) vasodilatations in forearm vasculature by strain-gauge plethysmography. Healthy individuals (n=14) served as baseline controls. RESULTS: The percentage increase by acetylcholine in the flow of the infused arm relative to the non-infused arm of coronary heart disease patients during the trial remained unaltered, but vasodilatation to NG-monomethyl-l-arginine+acetylcholine was improved by 161+/-27% with UDCA vs 83+/-22% with placebo (mean difference 91% [95% CI 35%, 147%], P=0.016). CONCLUSIONS: Six weeks' UDCA therapy improved endothelium-dependent nitric oxide-independent vasodilatation, which might maintain arterial flow in coronary heart disease patients under conditions of impaired nitric oxide production.

Metabolic syndrome is associated with changes in D-mannose metabolism.

Serum mannose concentration increases in diabetic patients and correlates closely with blood glucose. In patients with glomerulonephritis, serum mannose and mannose/glucose ratio positively correlate with dyslipidemia and the extent of urinary protein excretion. We investigated whether changes in serum mannose mark subjects with features of metabolic syndrome, including obesity, hypertension, glucose intolerance, and dyslipidemia. The study comprised 20 patients with mean age of 68 (SD 11) years, body mass index 27.2 (SD 5.1) kg/m2, blood glucose 6.2 (SD 1.6) mmol/L, serum total cholesterol 6.3 (SD 1.2) mmol/L, triglyceride 2.0 (SD 0.08) mmol/L, uric acid 320 (SD 109) micromol/L, mannose 60.0 (SD 17) micromol/L, and mannose/glucose ratio 9.7 (SD 1.8) micromol/mmol. Serum mannose correlated with blood glucose (r=0.758, p=0.012), triglyceride (r=0.478, p=0.023), and HDL-cholesterol (r = approximately 0.427, p=0.022). Mannose/glucose ratio correlated with BMI (r=0.581, p=0.033), mannose (r=0.491, p=0.035), and uric acid (r=0.608, p=0.027). The rate of VLDL lipoprotein turnover may be instrumental in the regulation of serum mannose concentration. We conclude that an altered mannose metabolism is a novel consideration among the metabolic abnormalities in the metabolic syndrome.

Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial.

BACKGROUND: Systolic hypertension increases the risk of dementia in elderly people. The vascular dementia project, set up in the framework of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial, investigated whether antihypertensive drug treatment could reduce the incidence of dementia. METHODS: Eligible patients had no dementia, were at least 60 years old, and had a blood pressure when seated of 160-219 mm Hg systolic and below 95 mm Hg diastolic. Active treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both drugs, titrated or combined to reduce the systolic blood pressure by at least 20 mm Hg to reach a value below 150 mm Hg. Cognitive function was assessed by the mini mental state examination (MMSE). If the MMSE score was 23 or less, diagnostic tests for dementia were done (DSM-III-R criteria). The cause of dementia was established by the modified ischaemic score with brain imaging or the Hachinski score. FINDINGS: Median follow-up by intention to treat was 2.0 years. Compared with placebo (n=1180), active treatment (n=1238) reduced the incidence of dementia by 50% from 7.7 to 3.8 cases per 1000 patient-years (21 vs 11 patients, p=0.05). The median MMSE score at randomisation was 29 in both treatment groups. At the last available assessment, systolic and diastolic blood pressure were, respectively, 8.3 mm Hg and 3.8 mm Hg lower (p<0.001) in the active-treatment group, but on average the MMSE scores did not change in either group. In the control patients, however, the MMSE decreased (p=0.04) with decreasing diastolic blood pressure, whereas in the active-treatment group MMSE scores improved slightly (p=0.01) with greater reduction in diastolic blood pressure (p=0.002 for between-group difference). INTERPRETATION: In elderly people with isolated systolic hypertension, antihypertensive treatment was associated with a lower incidence of dementia. If 1000 hypertensive patients were treated with antihypertensive drugs for 5 years 19 cases of dementia might be prevented.

Quality of life of elderly patients with isolated systolic hypertension: baseline data from the Syst-Eur trial. Syst-Eur Trial Investigators.

OBJECTIVE: To describe measures of quality of life of elderly patients with isolated systolic hypertension at entry to a placebo-controlled randomized trial of antihypertensive treatment and to investigate factors associated with these. DESIGN: Cross-sectional analyses at entry to a randomized controlled trial. SETTING: Patients attending hypertension clinics or general practitioners' surgeries at 30 centres in 10 European countries. PATIENTS: Six hundred and thirty-one patients aged 60 years or more, with a sitting systolic blood pressure during the run-in phase of 160-219 mmHg, a sitting diastolic blood pressure below 95 mmHg and a standing systolic blood pressure of 140 mmHg or more. MAIN OUTCOME MEASURES: Cognitive function tests (Reitan Trail Making A and B), Brief Assessment Index (a measure of depressed mood) and four subscales from the Sickness Impact Profile (Ambulation, Social Interaction, Sleep and Rest and Housework). RESULTS: Poor quality of life was generally associated with increasing age, previous treatment with antihypertensive drugs, presence of cardiovascular complications and, among women, high diastolic blood pressure, higher consumption of alcohol and high body mass index. CONCLUSIONS: At entry to the trial there was considerable heterogeneity of patients in terms of measures of quality of life and cognitive performance. It remains to be determined whether these influence subsequent quality of life during randomized treatment.