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Biomedical subjects

K Kervinen

Publications and source records attributed to K Kervinen.

At least 37 records · Page 2Linked to original sources

Apolipoprotein E phenotype and diet-induced alteration in blood pressure.

The purpose of the study was to answer the following two questions. First, are the diet-induced changes in the plasma cholesterol concentration associated with a change in blood pressure? Second, is the possible diet-induced change in blood pressure related to the apolipoprotein E (apo E) phenotype? Two hundred employees of our hospital volunteered and among those, 23 subjects with the apo E3 (E3,3) and 21 with the apo E4 phenotype (E4,3 or 4,4) were selected. The apo E groups were age- and sex-matched. Study subjects were healthy, had normal body weights, and their mean (+/-SD) age was 37.9 +/- 7.7 y. The total energy derived from dietary fat was 37%, 26%, and 38% during the baseline, low-fat, and high-fat diet periods, respectively. The two intervention diets were consumed by the study subjects for 4 wk at a time. During the trial blood pressure was measured once a week with an automatic device under standardized conditions. Systolic, diastolic, and mean arterial pressures were significantly reduced during the low-fat diet period compared with baseline, but not compared with the high-fat diet period among the apo E4 subjects only (-6%, -4.5%, and -6%, respectively). The high-fat diet was associated with elevation of blood pressure among 70% of study subjects. A slight but significant positive correlation was noted between the plasma total cholesterol concentration and blood pressure, more so among the apo E4 subjects. Furthermore, age was correlated with blood pressure response in apo E4 subjects. In conclusion, both the systolic and diastolic blood pressures were significantly altered during the different diet periods. The dietary response of blood pressure seemed to differ between subjects with the apo E4 and those with the apo E3 phenotype.

Adult↗

Effect of apolipoprotein E phenotype on plasma lipids and lipoproteins in alcohol abusers.

The effect of apolipoprotein (apo) E phenotype on the concentration and chemical composition of plasma lipoproteins was studied in 73 male alcohol abusers and 50 male controls. The apo E phenotype was confirmed by genotyping to avoid possible effects of posttranslational modifications by alcohol or its metabolites. The lipid and protein concentrations of both intermediate density lipoprotein and low density lipoprotein were lower among the alcohol abusers than among the controls, those with E4 having the highest low density lipoprotein masses in both groups. In the alcohol abusers with E4 only the high density lipoprotein (HDL)-2 lipid and protein concentrations were higher than in the controls with respective phenotype group, whereas both HDL2 and HDL3 were higher in alcohol abusers with other apo E phenotypes, suggesting that apo E modulates the alcohol-effect on HDL subfractions. This effect was not explained by cholesteryl ester transfer protein activity, which was lower in the alcohol abusers (25 to 34%, p < 0.01), but without significant difference between the apo E groups. In conclusion, alcohol abuse does not cause major changes in the electric charge of apo E in humans. Heavy alcohol intake seems to have a beneficial effect on plasma lipids and lipoproteins, regardless of the apo E phenotype, but the modulation of the alcohol-induced increase in HDL by apo E phenotype should be taken into consideration in future studies.

Adult↗

Association of lipoprotein cholesterol and triglycerides with the severity of coronary artery disease in men and women.

The differences between the lipid profiles of male and female patients and the effect of plasma lipids on the extent of coronary artery disease were evaluated in 122 angiographically assessed coronary artery disease patients (95 males and 27 females) and 60 controls. Both male and female patients had lower HDL-cholesterol and higher total cholesterol, LDL-cholesterol, triglyceride, VLDL-cholesterol and VLDL-triglyceride concentrations than the controls. The VLDL lipid values did not differ significantly between the male patients with different extent of CAD, whereas the VLDL lipid values of female patients tended to increase with an increasing severity of CAD. High Lp(a) (> or = 35 mg/dl) values were more prevalent in patients with > 50% coronary stenosis compared to patients with < 50% stenosis and the controls (29%, 17% and 12%, respectively). The apolipoprotein E phenotypes and epsilon allele frequencies were similar in the patients and the controls. Low HDL-cholesterol and high LDL-cholesterol are CAD risk factors for both sexes. For women, elevated VLDL-triglycerides seem to be an additional risk factor for CAD.

Adult↗

Memory functions in human subjects with different apolipoprotein E phenotypes during a 3-year population-based follow-up study.

The apolipoprotein E epsilon4 allele is the most common risk factor for Alzheimer's disease (AD). The epsilon2 allele may play a protective role in AD. Our previous cross-sectional study showed that in non-demented elderly subjects the epsilon2 allele is associated with better learning ability than other alleles. We wished to investigate the influence of different apolipoprotein E (apoE) phenotypes on cognitive functions in a 3-year follow-up study starting with a random sample of 917 non demented elderly subjects. Episodic memory was examined with the List Learning Test (Buschke's selective reminding method), as well as with immediate and delayed recall of figures. Retrieval from semantic memory was assessed with the Category and Verbal Fluency tests. Constructional abilities were examined by copying figures. Attention functions were examined with the Trail Making A and B tests. A total of 632 subjects completed the 3-year follow-up study. The subjects with apoE phenotypes E2/2 or E2/3 were able to maintain their verbal learning performance, while the learning ability of the subjects with other apoE phenotypes deteriorated. We suggest that successful mental aging may be at least in part associated with genetic factors.

Aged↗

Is the development of adenoma and carcinoma in proximal colon related to apolipoprotein E phenotype?

BACKGROUND & AIMS: Alterations in plasma lipoprotein levels and bile acid metabolism observed in patients with colorectal adenoma and carcinoma may reflect a genetic background predisposing to altered lipid metabolism and tumors. This study was designed to determine whether the polymorphism of apolipoprotein E, one of the key regulatory proteins in cholesterol metabolism, is associated with proximal or distal colonic neoplasia. METHODS: Apolipoprotein E phenotype was determined in 135 patients with colorectal adenoma, 122 patients with colorectal carcinoma, and 199 randomly selected control subjects. RESULTS: The frequency of the epsilon 4 allele of apolipoprotein E was low (0.075 and 0.073) in patients with proximal adenoma and those with carcinoma, respectively, compared with the control subjects (0.181) (P < 0.05). In patients with distal tumors, there was no alteration in epsilon 4 frequency. In all subjects with the epsilon 4 allele compared with subjects without epsilon 4, the odds ratio for proximal adenoma was 0.36 (95% confidence interval, 0.14-0.89), and the odds ratio for proximal carcinoma was 0.35 (95% confidence interval, 0.14-0.86). CONCLUSIONS: The data suggest that the epsilon 4 allele of apolipoprotein E provides protection from the development of adenoma and carcinoma of the proximal colon. These results support the theory that there are common susceptibility genes modulating the susceptibility to external carcinogenic factors.

Adenoma↗

Apolipoprotein E phenotype modifies metabolic and hemodynamic abnormalities related to central obesity in women.

Apolipoprotein E (apo E) is a normal constituent of very-low-density lipoproteins and it participates in the metabolism of both low-density lipoproteins (LDL) and apo E-containing lipoproteins. In the present study, the aim was to examine to what extent apo E phenotypes modify central obesity-induced changes in serum lipids, insulin, and blood pressure in obese women. Altogether, 143 middle-aged obese women with a body mass index (in kg/m2) of 28.0-43.0 were examined. Twelve had apo E 3,2 phenotype, 93 had apo E 3,3 phenotype, and 38 had either apo E 4,3 or 4,4 (4,3 + 4,4 group) phenotype. Serum total and LDL cholesterol were lower in the apo E 3,2 group than in other groups, but no significant differences were observed in other lipid variables in this regard. Both systolic and diastolic blood pressure measures tended to be lowest in subjects with apo E 3,2 phenotype and highest in those with apo E 4,3 or 4,4 phenotype (P = 0.08-0.15 for trend). When serum lipids, blood pressure, and insulin were analyzed by waist circumference and apo E phenotype group, it became evident that women who had central obesity and the apo E 4 allele had the highest blood pressures, insulin-glucose ratios, and insulin concentrations. These results suggest that apo E phenotype significantly modifies the central obesity-induced changes in metabolic and hemodynamic variables characteristic of insulin resistance.

Adult↗

The effects of monounsaturated-fat enriched diet and polyunsaturated-fat enriched diet on lipid and glucose metabolism in subjects with impaired glucose tolerance.

OBJECTIVE AND SUBJECTS: The effects of a high-fat, monounsaturated-fat enriched (Mono) diet and a reduced-fat, polyunsaturated-fat enriched (Poly) diet on lipid and glucose metabolism were compared in 31 subjects with impaired glucose tolerance. DESIGN AND INTERVENTIONS: After 3 weeks on a Run-in diet (37; 18:11:5, indicating energy percentages from total fat; saturated:monounsaturated:polyunsaturated fatty acids in the actual diets) subjects were randomized into a Poly-diet (34; 11:10:10) or a Mono-diet (40; 11:19:8) for 8 weeks. RESULTS: In the Mono group fasting plasma glucose (mean +/- SD) was lower after the test diet than after the run-in period (6.4 +/- 1.3 vs 6.0 +/- 0.8 mmol/L, 0 vs 8 weeks, P = 0.008), but remained unchanged in the Poly group (6.2 +/- 0.6 vs 6.1 +/- 0.7 mmol/L). Glucose effectiveness (SG), insulin sensitivity index and the first phase insulin response in an intravenous glucose tolerance test did not change significantly during either of the diets, but at the end of the study SG was higher in the Mono group than in the Poly group (P = 0.013). Serum total cholesterol, LDL cholesterol, and apolipoprotein B decreased in the Mono group, while in the Poly group only serum total cholesterol decreased significantly. However, the mean changes in serum lipids and lipoproteins did not differ significantly between the groups. CONCLUSIONS: In free-living subjects with impaired glucose tolerance both the Mono-diet and the Poly-diet consumed after a saturated-fat enriched Run-in diet improved serum lipid profile and the Mono-diet seemed to improve glucose metabolism as well.

Body Mass Index↗

The association of apolipoprotein E polymorphism with memory: a population based study.

Several studies have shown an association between the apolipoprotein epsilon 4 allele and Alzheimer's disease (AD). The allele epsilon 2 has been associated with survival and longevity. We wanted to examine whether the relationship between cognitive efficiency and apolipoprotein E polymorphism (APOE) exists in a random sample of 916 non-demented elderly subjects. Episodic memory was examined with the list learning test, and with immediate and delayed recall of the figures. Semantic memory was examined with the Category and Verbal Fluency Tests. Constructional abilities were examined by copying the figures. Attention functions were examined with Trail Making A and B tests. We found that subjects with APOE E2/2 and 2/3 phenotypes showed better learning ability than those subjects with the APOE E2/4, 3/4 or 4/4 phenotypes. Impaired memory was not related to the excess of cardiovascular diseases in the subjects with APOE E2/4, 3/4, 4/4 phenotypes. Thus they may be associated, at least partly, with genetic factors.

Aged↗

Apolipoprotein E4 phenotype is not an important risk factor for coronary heart disease or stroke in elderly subjects.

The allele e4 (apo e4) of apolipoprotein E (apo E) has been associated with an increased risk for coronary heart disease (CHD) in cross-sectional studies in middle-aged subjects. We investigated the risk of CHD and stroke with respect to the number of apo e4 alleles in a prospective study of a Finnish nondiabetic cohort including 1067 subjects 65 to 74 years old at baseline. During the 3.5-year follow-up, CHD mortality was 2.8%, total CHD incidence 6.9%, and the cumulative occurrence of CHD (prevalence at baseline and the 3.5-year incidence combined) 17.0%. The incidence of stroke was 3.4%, and the cumulative occurrence of stroke was 6.0%. The CHD mortality was 3.4% in subjects with no apo e4 allele (n = 734), 1.7% in those with one apo e4 allele (n = 296), and 0% in subjects with two apo e4 alleles (n = 37) (P = NS between the three groups). The incidence of CHD according to the number of apo e4 alleles was 6.9% (no apo e4 alleles), 7.4% (one apo e4 allele), and 2.7% (two apo e4 alleles), and the cumulative occurrence of CHD was 16.5%, 18.6%, and 13.5%, respectively (P = NS). The incidence of stroke was 3.8% in subjects with no apo e4 allele, 2.7% in those with one apo e4 allele, and 0% in those with two apo e4 alleles (P = NS). The cumulative occurrence of stroke was 6.0%, 6.4%, and 2.7%, respectively (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Association of apolipoprotein E phenotypes with late onset Alzheimer's disease: population based study.

OBJECTIVE: To determine the association between the e4 allele of apolipoprotein E and Alzheimer's disease in a randomly selected population sample. DESIGN: Cross sectional population based study. SUBJECTS: 980 people aged 69 to 78 (349 men, 631 women). SETTING: Population of Kuopio, eastern Finland. MAIN OUTCOME MEASURES: Presence of e4 allele and diagnosis of Alzheimer's disease by detailed neurological and neurophysiological evaluation. RESULTS: 46 (4.7%) subjects were classified as having probable or possible Alzheimer's disease. The frequency of the apolipoprotein E e4 allele was 0.359 in patients with Alzheimer's disease and 0.165 subjects without dementia (P < 0.0001). The prevalence of Alzheimer's disease was 2.9% in subjects with no e4 alleles, 7.6% in subjects with one e4 allele, and 21.4% in subjects with two e4 alleles of apolipoprotein E. CONCLUSIONS: Allele e4 of apolipoprotein is associated with Alzheimer's disease in a dose-response fashion in a randomly selected elderly population.

Aged↗

Long-term effects of three fat-modified diets in hypercholesterolemic subjects.

Altogether 160 free living subjects (aged 30-60 years) most of whom had moderate hypercholesterolemia were randomised into the following diet groups to find out long-term effects of different fat-modified diets: (1) control diet 35/14:10:4 (energy percents from fat/saturated:monounsaturated:polyunsaturated fatty acids in actual diets); (2) AHA type diet 32/10:8:8; (3) monoene-enriched diet 34/11:11:5; (4) reduced-fat diet 30/12:8:3. LDL cholesterol fell equally with the AHA type diet (4.54 +/- 0.97 vs. 4.21 +/- 0.89 mmol/l (mean +/- S.D., 0 vs. 6 months), P = 0.001) and with the monoene-enriched diet (4.55 +/- 0.95 vs. 4.25 +/- 0.95 mmol/l, P = 0.004) during the 6-month study. Moderate amounts of polyenes or monoenes as part of natural diets did not decrease HDL cholesterol level in the long term. Serum lipid values remained unchanged with the reduced-fat diet. Analysis by apolipoprotein E phenotypes showed a decrease in LDL cholesterol only in subjects with phenotype 3/3 in the monoene-enriched group (-8.6 +/- 8.7 vs. +1.3 +/- 15.4, percent change in LDL cholesterol E 3/3 vs. E 4/3 + 4/4), but in the AHA type group LDL cholesterol decreased similarly in phenotypes E 3/3 and E 4/3 + 4/4 (-6.9 +/- 10.1 vs -6.9 +/- 16.5).

Adult↗

Apolipoprotein E and B polymorphisms--longevity factors assessed in nonagenarians.

To test if the prevalence of genetic risk factors for coronary heart disease (CHD) is low in individuals who have reached an extremely old age, the allele frequencies of apolipoprotein E (apo E) and B (apo B) polymorphisms and plasma lipoprotein(a) levels were investigated in nonagenarians and in younger control groups. The frequency of the epsilon 4 allele of apo E was significantly lower in the nonagenarians than in the middle-aged and young adults (P < 0.05). Also, the frequency of EcoRI allele R- of apo B was low in the nonagenarians, whereas the allele frequency for the XbaI polymorphism of apo B and plasma lipoprotein(a) concentrations did not differ between the nonagenarians and the younger groups. These findings strongly suggest that the presence of these potential genetic risk factors for CHD, namely the epsilon 4 allele of apo E and the R- allele of apo B, decreases the probability of an individual reaching an extremely old age.

Adult↗

Decreased clearance of uraemic and mildly carbamylated low-density lipoprotein.

Low-density lipoprotein (LDL) was in vitro carbamylated with potassium cyanate and the clearance was studied in man. A minor carbamylation of LDL decreased the clearance of LDL by 41% (94% of amino groups free) and by 18% (90% of amino groups free). When LDL was extensively carbamylated its clearance was substantially accelerated. Moreover, the clearance of LDL isolated from 14 haemodialysis patients (uremic-LDL) was studied in rabbits. Uraemic-LDL, injected into rabbits simultaneously with the LDL of a healthy control subject, was cleared more slowly than the control-LDL (difference in fractional catabolic rate -6.5%, P = 0.02). We also examined the lipid peroxidation of the carbamylated LDL by measuring the amount of thiobarbituric-acid reactive substances (TBARS) and formation of conjugated dienes during exposure of carbamylated LDL to 5 microM Cu2+. The carbamylated and native LDL had similar lipid peroxidation and propensity for oxidation. In summary, both the uraemic-LDL and minimally carbamylated LDL had a decreased clearance in vivo, which may contribute to the accelerated atherosclerosis in uraemic patients.

Adult↗

Effects of three treatment modes on plasma lipids and lipoproteins in uraemic patients.

Plasma lipids, chemical composition of various lipoprotein fractions, apolipoprotein B concentrations and apolipoprotein E phenotypes were studied in 12 uraemic patients on conservative treatment (CT), in 16 patients on haemodialysis (HD) and in 18 patients on continuous ambulatory peritoneal dialysis treatment (CAPD). Plasma total cholesterol and triglyceride concentrations were increased in the CAPD patients in comparison to the HD patients and the control subjects. Moreover, the CAPD patients had higher LDL cholesterol concentration than the CT and HD patients. The HDL cholesterol concentration was lower in the HD and CAPD patients than in the control subjects. The chemical composition of lipoproteins in all fractions of the CT and HD patients and in VLDL, IDL and LDL fractions of the CAPD patients differed from those of the control subjects. The main differences were the increased proportion of triglycerides in VLDL and LDL fractions of all the patient groups and in HDL fraction of the CT and HD patients in comparison to the control subjects. Moreover, the proportion of cholesterol was increased in VLDL and IDL fractions of the CT and the CAPD patients and decreased in HDL fraction of the CT and HD patients compared to the control subjects. In conclusion, in addition to the alterations in the lipoprotein concentrations in uraemic patients there are also marked changes in the chemical composition of the lipoprotein particles that may further contribute to the accelerated atherosclerosis among uraemic patients. The abnormalities are particularly prevalent in CAPD patients.

Adult↗

Gallstone cholesterol content is related to apolipoprotein E polymorphism.

BACKGROUND: The genetically determined phenotypes of apolipoprotein E are related to variations in lipoprotein levels and in the enterohepatic metabolism of cholesterol and bile acids. The present study was designed to elucidate the role of apolipoprotein E polymorphism in gallstone formation. METHODS: Apolipoprotein E phenotype was determined in 169 consecutive cholecystectomy patients and in 200 controls. The cholesterol content of the gallstones (n = 169), the presence of cholesterol monohydrate crystals of fresh gallbladder bile (n = 142), and the nucleation time (n = 35) were also analyzed. RESULTS: The median cholesterol content of the gallstones was higher in the apolipoprotein E4 category (phenotypes E4/4 and E4/3, 97%) than in the E3 (E3/3, 78%) and E2 patients (E2/2 and E2/3, 76%, P = 0.0003). In E4 patients, cholesterol crystals were found immediately after surgery in 27 of 40 (68%), whereas in E3 and E2 groups in 36 of 88 (41%), and 4 of 14 (29%) of the patients (P = 0.0001). The median nucleation time in E4 patients (2.5 days) was shorter than in patients with E3 (5.5 days) or E2 (6.0 days) (P = 0.0016). CONCLUSIONS: These data indicate that apolipoprotein E polymorphism affects cholesterol content of cholelithiasis. We suggest that this phenomenon is mediated by the altered formation of cholesterol monohydrate crystals in different apolipoprotein E phenotypes.

Adult↗

Apolipoprotein E phenotype is related to macro- and microangiopathy in patients with non-insulin-dependent diabetes mellitus.

The role of apoliprotein E (apo E) in modulating the susceptibility of individuals with non-insulin-dependent diabetes mellitus (NIDDM) to atherosclerotic vascular disease was studied in 143 male and 128 female patients with NIDDM. The data show that the apolipoprotein phenotype E2 somehow protects from macrovascular complications in NIDDM both in men and women. E2 also tends to protect from microvascular complications. In contrast, apo E phenotypes E4/4 and E4/3 tend to increase the risk for macroangiopathy in NIDDM patients. The lower prevalence of macroangiopathy in the subjects with E2 was associated with lower plasma total and LDL cholesterol concentrations and low plasma lipoprotein(a) levels. Overall, this study demonstrates the role of the apo E phenotype to modulate the risk for diabetic complications in patients with NIDDM. The confirmation of the association of apo E polymorphism with diabetic complications warrants, however, long-term follow-up studies.

Apolipoproteins E↗