Three-year outcomes related to coronary stenting; a registry-based real-life population study.

Objectives. Developments in medication and coronary interventions have improved coronary artery disease (CAD) treatment. We studied long-term outcomes in an observational, real-life population of CAD patients undergoing percutaneous coronary intervention (PCI) depending on the presentation and the stent type used. Design and results. Register included 789 consecutive patients undergoing PCI. Follow up period was three years with primary composite outcome (MACE) of all cause -mortality, myocardial infarction and target lesion revascularization. Mean age was 65 ± 11 and 69% were male. New-generation drug-eluting stents (DES-2) were associated with lower adjusted rates of MACE (HR 0.47; 95% CI 0.29-0.77) but not mortality (HR 0.50; 95% CI 0.22-1.14) in comparison to bare-metal stents. Patients with STEMI (14.4%) or NSTEMI (13.7%) had higher crude mortality rates than those with unstable (4.5%) or stable CAD (3.1%; p < .001). The association diminished after adjustments in NSTEMI (HR 2.01; 95% CI 0.88-4.58). Among smokers 45% quitted and 36% achieved recommended cholesterol levels. Conclusions. The overall prognosis was good. Irrespective of comorbidities, NSTEMI was not associated with worse outcome than stable CAD. DES-2 was associated with lower rates of MACE than BMS without affecting mortality rate. Patients succeeded better in smoking cessation than reaching recommended cholesterol levels.

Outcome of ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome treated with titanium-nitride-oxide-coated versus everolimus-eluting stents: insights from the BASE-ACS trial.

AIM: The BASE-ACS trial demonstrated an outcome of titanium-nitride-oxide-coated bioactive stents (BAS) that was statistically non-inferior to that of everolimus-eluting stents (EES) at 12-month follow-up, in patients presenting with acute coronary syndrome (ACS) who underwent early percutaneous coronary intervention (PCI). We explored a post-hoc analysis of the 12-month outcome of the BASE-ACS trial in the subgroup of patients with ST-elevation myocardial infarction (STEMI) versus non-ST-elevation ACS (non-STEACS). METHODS: A total of 827 patients with ACS (321 STEMI) were randomly assigned to receive either BAS or EES. The primary endpoint was a composite of cardiac death, non-fatal myocardial infarction (MI) and ischemia-driven target lesion revascularization (TLR) at 12-month follow-up. RESULTS: The 12-month cumulative incidence of the primary endpoint was similar between the two subgroups (9% versus 9.5%, in STEMI versus non-STEACS patients respectively, P=0.90). The 12-month rate of cardiac death was significantly higher in the STEMI subgroup as compared with the non-STEACS subgroup (2.8 versus 0.6%, respectively, P=0.01). However, the rates of non-fatal MI, ischemia-driven TLR, definite stent thrombosis, and non-cardiac death were all statistically matched between the two subgroups (P>0.05 for all). CONCLUSION: In the current post-hoc analysis of the BASE-ACS trial based on the infarction type, the 12-month outcome of patients who underwent early PCI for ACS was slightly worse in the setting of STEMI as compared with non-STEACS, as reflected by a significantly higher rate of cardiac death.

Risk of dementia associated with the ApoE epsilon4 allele and falls causing head injury without explicit traumatic brain injury.

OBJECTIVES: Severe head injury (HI) and the apolipoprotein E (ApoE) epsilon4 allele are risk factors for dementia. The corresponding effect of falls causing HI without explicit traumatic brain injury (TBI) in association with the ApoE epsilon4 is not known. MATERIALS AND METHODS: Altogether 134 persons aged 70 years or older constituted a retrospective population sample, who scored > or =26 in the MiniMental State Examination (MMSE) test at baseline and were clinically examined for dementia 9 years afterward. Fall-related HI causing superficial laceration or bruises or wounds that require suturing were prospectively recorded during the 9-year follow-up. We used Cox regression with age at the diagnosis of dementia as a dependent variable. RESULTS: Twenty-eight (21%) subjects had falls causing HI without explicit TBI, the ApoE epsilon4 allele was seen in 44 (33%), and clinical dementia was diagnosed in 25 (19%). Adjusted for the baseline MMSE score, sex and educational status, the hazard ratio for subsequent dementia in subjects having falls with HI without explicit TBI and the ApoE epsilon4 allele as compared with those who do not possess these characteristics was 2.70 (95% confidence interval, 1.02-7.16). CONCLUSIONS: According to the results of this small retrospective study, falls with HI without explicit TBI in connection with the ApoE epsilon4 allele is associated with subsequent dementia among older adults.

Association of metabolic syndrome with Alzheimer disease: a population-based study.

OBJECTIVE: To assess the association of metabolic syndrome (MetS) with Alzheimer disease (AD). METHODS: The authors derived subjects from a population-based study of 980 randomly selected elderly subjects. After exclusion of all non-Alzheimer dementia cases, the final study population included 959 subjects (337 men and 622 women) aged 69 to 78 years. The presence of MetS was defined according to the National Cholesterol Education Program (Adult Treatment Panel III) criteria, and the diagnosis of AD was based on the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. RESULTS: Of the study subjects, 418 (43.6%) had MetS. Probable or possible AD was diagnosed in 45 subjects (4.7%). AD was more frequently detected in subjects with MetS than in subjects without MetS (7.2 vs 2.8%; p < 0.001). The prevalence of AD was higher in women with MetS vs women without the syndrome (8.3 vs 1.9%; p < 0.001), but in men with MetS, the prevalence of AD was not increased (3.8 vs 3.9%; p = 0.994). In univariate logistic regression analysis, MetS was significantly associated with AD (odds ratio [OR] 2.71; 95% CI 1.44 to 5.10). In multivariate logistic regression analysis including also apolipoprotein E4 phenotype, education, age, and total cholesterol, MetS was significantly associated with AD (OR 2.46; 95% CI 1.27 to 4.78). If only nondiabetic subjects were included in the multivariate analysis, MetS was still significantly associated with AD (OR 3.26; 95% CI 1.45 to 7.27). CONCLUSION: Metabolic syndrome is associated with Alzheimer disease in elderly subjects.

Fall-related brain injuries and the risk of dementia in elderly people: a population-based study.

Severe head injury in early adulthood may increase the risk of dementia in older age, but it is not known whether head injury in later life also increases the risk of dementia. A representative sample (82%) of persons aged 70 years or older with a Mini-Mental State Examination (MMSE) test score of > or =26 (n = 325) were followed-up for 9 years to record all their fall-related head injuries resulting in traumatic brain injury (TBI). At the end of the follow-up period, 152 persons (81% of the surviving population) were examined for clinical dementia, according to DSM-IV criteria. Eight persons sustained a TBI and 34 developed dementia. Brain injury was associated with younger age at detection of dementia even when adjusted for sex and educational status (low educational status significantly associated with dementia); age-specific hazard ratio (95% confidence interval) 2.80 (1.35-5.81). In a population scoring > or =28 points in the baseline MMSE an apolipoprotein E (ApoE) epsilon4 phenotype was also associated with younger age at the time of detecting dementia; 3.56 (1.35-9.34), and the effect of brain injury and ApoE epsilon4 phenotype was synergistic; 7.68 (2.32-25.3). We conclude that fall-related TBI predicts earlier onset of dementia and the effect is especially high amongst subjects who carry the ApoE epsilon4 allele.

Risk factors for cryptogenic ischaemic stroke.

This case-control study was designed to identify risk factors for cryptogenic brain infarction. We assessed the frequency of prothrombotic states, homocysteine, lipoprotein (a) [Lp(a)] and other lipids and the apolipoprotein E phenotype together with conventional risk factors in 46 patients (19 women and 27 men) with cryptogenic brain infarction aged from 15 to 60 years and in 104 community-based controls. Multivariate odds ratios (ORs) for risk factors and 95% CIs were calculated by logistic regression. Hypertension (OR 4.5; 95% CI, 1.5-13.2; P = 0.006), current smoking (OR 2.9; 95% CI, 1.2-6.8; P = 0.012), low HDL cholesterol (HDL-C) (OR 5.4; 95% CI, 1.1-25.5; P = 0.035) and high clotting factor VIII activity (OR 3.6; 95% CI, 1.1-12.2; P = 0.041) were variables associated with cryptogenic brain infarction. These risk factors were not equally frequent in women and men. Low HDL-C and high factor VIII activity in the women, and hypertension, current smoking and a low level of plasma folate in the men were risk factors for cryptogenic stroke. Several of the observed risk factors for cryptogenic brain infarction were lifestyle-associated, which emphasizes the role of health education in addition to pharmacological treatment in the prevention of stroke.

Endothelial nitric oxide synthase gene Glu298Asp polymorphism and blood pressure, left ventricular mass and carotid artery atherosclerosis in a population-based cohort.

OBJECTIVE: Decreased production of endothelial nitric oxide (NO) is associated with different cardiovascular pathology. We studied the association between the Glu298Asp polymorphism of the NO producing gene, endothelial nitric oxide synthase (eNOS), and hypertension, left ventricular mass (LVM) and carotid artery intima-media thickness (IMT) in a population-based cohort of hypertensive and control subjects. DESIGN: Cross-sectional case-control study. SETTING: District around Oulu University Hospital, Northern Finland. SUBJECTS AND METHODS: The study population consisted of 600 middle-aged hypertensive subjects (300 men and 300 women) and 600 controls (300 men and 300 women) living in the City of Oulu. The hypertensive subjects were randomly selected by age stratification from the Social Insurance Institute register for reimbursement of antihypertensive medication. For each hypertensive subject, an age- and sex-matched control was randomly selected from the national health register. The overall participation rate was 87.8%. In the present study a total of 1024 subjects were screened. Echocardiographic examinations were performed by a trained cardiologist and carotid ultrasonographic examinations by a trained radiologist. RESULTS: The genotype distributions and allele frequencies between the hypertensive and control subjects and the relationship between the Glu298Asp variant and blood pressure, LVM and carotid artery IMT were determined. No differences in genotype distribution or allele frequencies were found between the hypertensive and control groups (the frequency of the Asp allele 0.299 vs. 0.288, respectively). Also, we could not find any association between the eNOS genotype and the measured cardiovascular complications. CONCLUSIONS: The Glu298Asp variant of the eNOS gene does not seem to be a major risk factor for cardiovascular alterations in the general population.

APOE-epsilon4 is associated with weight loss in women with AD: a population-based study.

OBJECTIVE: To investigate whether the APOE-epsilon4 allele is associated with weight loss in patients with AD or in nondemented elderly subjects. BACKGROUND: Weight loss has been considered a typical feature of AD. APOE-epsilon4 is a risk factor for AD and was recently proposed to be associated with weight loss in elderly women. It is not known whether APOE-epsilon4 is associated with weight loss in patients with AD or in the general population. METHODS: Weight and BMI measurements at an average interval of 3.5 years and APOE phenotype determination were performed in an elderly population (n = 980), including 46 patients with AD and 911 control subjects at the end of the follow-up. RESULTS: On average, patients with AD with the epsilon4 allele lost 1.9 +/- 4.0 kg (BMI 0.8 +/- 1.8 kg/m2) whereas epsilon4 noncarriers gained 1.2 +/- 3.8 kg (BMI 0.4 +/- 1.5 kg/m2) (both p < 0.05), after controlling for diabetes and exercise. However, when men and women were analyzed separately, weight loss was observed only in those women with AD with the epsilon4 allele. Clinically significant weight loss, defined as loss of > or = 5% of body weight, occurred more frequently in both patients with AD (30% versus 6%; p < 0.05) and control subjects (28% versus 18%; p < 0.001) carrying the epsilon4 allele. CONCLUSIONS: The APOE-epsilon4 allele may contribute to the unexplained weight loss in AD, especially in women.

Apolipoprotein E phenotype alone does not influence survival in Alzheimer's disease: a population-based longitudinal study.

Apolipoprotein E4 (ApoE4) phenotype is a known risk factor for development of Alzheimer's disease (AD). Contradictory results exist concerning the role of ApoE4 in the rate of decline and mortality in AD. Conflicting findings have also been reported about ApoE and gender interactions with respect to survival. We examined the survival of subjects with AD and non-AD controls with respect to ApoE phenotype and gender in a population-based longitudinal study. Cognitive evaluation was performed for a total of 980 subjects (then aged 69-78 years), and 48 cases with AD were identified. ApoE4 phenotype was more frequently present among subjects with AD. In the whole study population, survival was not related to the presence of AD or ApoE4 phenotype. Risk of death was increased for men compared to women, independently of the ApoE4 phenotype (HR 0.5, 95% confidence interval 0.44-0.69). In subjects with AD, the presence of ApoE4 alone did not influence survival. However, in the AD group, ApoE4-negative men had significantly increased risk of mortality compared to the risk in ApoE4-negative women (p < 0.01). We conclude that the presence of ApoE4 phenotype or AD did not influence mortality in the aged population. Once AD had become manifest, ApoE4 alone did not relate to survival. However, in subjects with AD not carrying ApoE4, men had reduced survival compared to women.

The apolipoprotein epsilon4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction : a substudy of the Scandinavian simvastatin survival study.

BACKGROUND: Carriers of the epsilon4 allele of the apolipoprotein E gene are at a higher risk of coronary heart disease than individuals with other genotypes. We examined whether the risk of death or a major coronary event in survivors of myocardial infarction depended on apolipoprotein E genotype and whether the benefits of treatment with simvastatin differed between genotypes. METHODS AND RESULTS: Cox proportional hazards models were used to analyze 5.5 years of follow-up data from 966 Danish and Finnish myocardial infarction survivors enrolled in the Scandinavian Simvastatin Survival Study. A total of 16% of the 166 epsilon4 carriers in the placebo group died compared with 9% of the 312 patients without the allele, which corresponds to a mortality risk ratio of 1.8 (95% confidence interval, 1.1 to 3.1). The risk ratio was unaffected by considerations of sex, age, concurrent angina, diabetes, smoking, and serum lipids in multivariate analyses. Simvastatin treatment reduced the mortality risk to 0.33 (95% confidence interval, 0.16 to 0.69) in epsilon4 carriers and to 0.66 (95% confidence interval, 0. 35 to 1.24) in other patients (P=0.23 for treatment by genotype interaction). Apolipoprotein E genotype did not predict the risk of a major coronary event. Baseline serum levels of lipoprotein(a) also predicted mortality risk and could be combined with epsilon4-carrier status to define 3 groups of patients with different prognoses and benefits from treatment. CONCLUSIONS: Myocardial infarction survivors with the epsilon4 allele have a nearly 2-fold increased risk of dying compared with other patients, and the excess mortality can be abolished by treatment with simvastatin.

Insulin-like growth factor binding protein-1 (IGFBP-1) and IGF-I during oral and transdermal estrogen replacement therapy: relation to lipoprotein(a) levels.

Low levels of insulin-like growth factor binding protein-1 (IGFBP-1) have recently been associated with several risk factors for cardiovascular disease. The effects of estrogen replacement therapy (ERT) on plasma IGFBP-1 levels are, however, unclear. A double-blind, placebo-controlled study for 6 months was conducted in 73 hysterectomized postmenopausal women randomized into two groups: oral estradiol (E2) valerate, 2 mg/day (n = 35) and transdermal E2 gel, 1 mg/day (n=38). Plasma IGFBP-1, insulin-like growth factor-I (IGF-I) and lipoprotein(a) (Lp(a)) were determined at baseline, 3 and 6 months. The groups were similar for age and BMI. The baseline levels of estrone (E1), E2, IGFBP-1, IGF-I and Lp(a) did not differ between the groups. During treatment, serum estradiol concentrations increased in both groups. During oral ERT, IGFBP-1 levels increased by 104% (P<0.001), whereas IGF-I levels decreased by 13% (mean, P<0.05). IGF-I and IGFBP-1 levels remained unchanged in the transdermal group. Lp(a) levels decreased by 23% (median, P<0.001) in the oral group, but were unaffected by transdermal therapy. The change in IGFBP-1 concentrations during oral ERT showed an inverse correlation to that in Lp(a) (r = -0.40, P<0.05, Spearman correlation). In conclusion, oral ERT seems to enhance plasma levels of IGFBP-1, which may be one reason for the reduced Lp(a) levels.

The effect of the apolipoprotein E phenotype on cholesteryl ester transfer protein activity, plasma lipids and apolipoprotein A I levels in hypercholesterolaemic patients on colestipol and lovastatin treatment.

BACKGROUND: Apolipoprotein E (apo E) allele E 4 is associated with high atherogenic lipid levels and coronary heart disease. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from (high density lipoprotein) HDL to other lipoproteins. CETP gene expression is enhanced in hypercholesterolaemia and correlates with plasma apo E concentration. OBJECTIVE: The effect of the apo E phenotype on plasma CETP activity and the hypolipidaemic efficacy of colestipol and lovastatin was studied in patients with type II a or II b hypercholesterolaemia. RESULTS: The baseline mean plasma total, low density lipoprotein (LDL) and HDL cholesterol, triglyceride, apolipoprotein A I (apo A I) concentrations and CETP activity were 8.89 mmol x l(-1), 6.78 mmol x l(-1), 1.39 mmol x l(-1), 1.59 mmol x l(-1), 1.49 g x l(-1) and 114 nmol x h(-1) x ml(-1), respectively. The colestipol-induced changes were -26%, -36%, +5%, + 12%, -1% and -17%, and the lovastatin-induced changes -34%, -44%, +6%, -18%, +1% and -19%. The lipid and apo A I concentrations or the CETP activity did not differ statistically significantly according to the apo E phenotype, although the HDL cholesterol and apo A I levels were lowered in patients with apo E 4/4 but elevated in patients with the other phenotypes. The CETP activity correlated with the LDL cholesterol concentration (r = 0.52, P = 0.01) and the change in the LDL cholesterol during colestipol (r = 0.51, P = 0.02) and lovastatin (r = 0.65, P = 0.001) treatment, but only in patients without the apo E 4 allele. CONCLUSION: Colestipol and lovastatin reduced CETP activity to the same amount, regardless of the apo E phenotype. The apo E phenotype seems to modify the interaction between CETP activity and LDL cholesterol in hypercholesterolaemia and during pharmacological lowering of cholesterol.

Glucose metabolism, insulin-like growth factor-I, and insulin-like growth factor-binding protein-1 after alcohol withdrawal.

Alcohol abusers often present with deteriorated glucose metabolism and insulin resistance. Changes in other glucoregulators, such as insulin-like growth factor-I (IGF-I) and IGF-binding protein-1 (IGFBP-1) may also be related to alcohol abuse. We studied the effects of alcohol withdrawal on blood glucose, serum insulin and C-peptide, and plasma IGF-I and IGFBP-1 levels in 27 noncirrhotic male alcoholics aged 43 +/- 9.0 (mean +/- SD) years on four consecutive days immediately after withdrawal. A 4-day monitoring period was conducted in four healthy nonalcoholic control men. The groups were similar in age and body mass index. Glucose, insulin, IGF-I, and IGFBP-1 did not differ significantly between the groups at the baseline, but C-peptide was higher in alcoholics (p < 0.01). After alcohol withdrawal, serum insulin and C-peptide levels increased in close correlation with each other (r = 0.82, p < 0.001). During the 4-day observation period in alcoholics, IGFBP-1 levels declined by 59%, whereas IGF-I increased by 41% (p < 0.001 for both comparisons). The change in insulin correlated inversely with the change in IGFBP-1 levels (r = -0.39, p < 0.05). In the control group, glucose, insulin, IGF-I, and IGFBP-1 remained unchanged during the 4-day monitoring period, whereas some reduction was observed in C-peptide. In conclusion, alcohol withdrawal enhances insulin production, as seen in increased C-peptide levels. An inverse correlation between the changes in insulin and that in IGFBP-1 might suggest that inhibition of IGFBP-1 by insulin remains largely unchanged during the acute phase of alcohol withdrawal.

The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects.

BACKGROUND: The polymorphism of apolipoprotein E has been suggested to be associated with the cholesterol content of gallstones, the crystallisation rate of gall bladder bile, and the prevalence of gallstone disease (GSD). AIMS: To investigate whether apolipoprotein E polymorphism modulates the susceptibility to GSD at the population level and to study the possible associations between impaired glucose tolerance, diabetes, and GSD. METHODS: Apolipoprotein E phenotypes were determined in a middle aged cohort of 261 randomly selected hypertensive men, 259 control men, 257 hypertensive women, and 267 control women. All subjects without a documented history of diabetes were submitted to a two hour oral glucose tolerance test (OGTT). GSD was verified by ultrasonography. RESULTS: In women with apolipoprotein E2 (phenotypes E2/2, 2/3, and 2/4) compared with women without E2 (E3/3, 4/3, and 4/4), the odds ratio for GSD was 0. 28 (95% confidence interval 0.08-0.92). There was no protective effect in men. The relative risk for GSD was 1.2 (0.8-1.7) for hypertensive women and 1.8 (1.0-2.7) for hypertensive men. In a stepwise multiple logistic regression model, E2 protected against GSD in women, whereas two hour blood glucose in the OGTT, serum insulin, and plasma triglycerides were risk factors. Elevated blood glucose during the OGTT was also a significant risk factor for GSD in men. CONCLUSIONS: The data suggest that apolipoprotein E2 is a genetic factor providing protection against GSD in women. In contrast, impaired glucose tolerance and frank diabetes are associated with the risk of GSD.

Apolipoprotein E phenotype determines the effect of alcohol on blood pressure in middle-aged men.

Apolipoprotein E (apoE) has an essential role in lipoprotein metabolism, but recent studies have also revealed other functions associated with it, eg, neurologic and malignant diseases. We studied the association between apoE phenotypes E2/3, E3/3, and E4/3 and blood pressure after adjustment for covariates, as well as the association between phenotypes and adjusted plasma glucose and insulin levels in the standard oral glucose tolerance test in a random middle-aged population-based cohort of 259 men and 267 women. Systolic blood pressure was associated with apoE phenotype in the men with moderate or heavy alcohol consumption (>115 g/week), the mean systolic blood pressure value being 16 mm Hg higher in the E2/3 and 11 mm Hg higher in the E3/3 phenotypes than in the E4/3 phenotype, P = .04. No association was seen in occasional drinkers or teetotalers (lowest tertile <24 g/week), whereas in the middle tertile the association was intermediate. The same association was seen with diastolic blood pressure. In men, there was a significant correlation between systolic blood pressure and alcohol consumption in the E2/3 phenotype (rs = 0.71, P < .01) and in the E3/3 phenotype (rs = 0.25, P < .01), but not in the E4/3 phenotype (rs = 0.03, NS). No association between apoE phenotypes and insulin resistance was observed. In conclusion, in middle-aged men, apoE phenotype significantly influences the blood-pressure-increasing effect of alcohol consumption. This gene environment interaction may have marked implications for the prevention and treatment of hypertension.

Serum lipids and apolipoprotein E phenotypes in identical twins reared apart.

Lipid and lipoprotein metabolism is controlled by genes, the environment and the gene environment interaction. We studied monozygotic twin pairs reared apart (MZA) and an age sex matched group of twins reared together (MZT) to evaluate the effects of the genotype and the rearing environment on lipids. The intraclass correlations for low density lipoprotein (LDL) cholesterol were 0.21 and 0.50 for the MZA and MZT groups, respectively, suggesting that the rearing environment possibly had an impact on the variability in LDL cholesterol later in life. The intraclass correlations for total cholesterol (0.26 and 0.47 for the MZA and MZT groups, respectively) reflected those for LDL cholesterol. The intraclass correlations for high density lipoprotein (HDL) cholesterol did not show any difference between the twin groups, suggesting that the rearing environment does not have major long-term effects on the variability of HDL levels. The intrapair differences for LDL cholesterol were smallest in the twins heterozygous for the apolipoprotein E allele epsilon2 (E2/3 and E2/4 phenotypes), intermediate in the pairs with the common E3/3 phenotype and enhanced in the pairs with E4/3 phenotype. To conclude, these data suggest that the rearing environment may play a role in the variability of LDL cholesterol levels, although variance difference between MZAs and MZTs, and the small number of available monozygotic twins reared apart limits the generalizability of the results.

Alcohol withdrawal-induced change in lipoprotein(a): association with the growth hormone/insulin-like growth factor-I (IGF-I)/IGF-binding protein-1 (IGFBP-1) axis.

Lipoprotein(a) [Lp(a)] is an important risk factor for cardiovascular disease. Alcohol is one of the few nongenetic factors that lower Lp(a) levels, but the metabolic mechanisms of this action are unknown. Alcohol inhibits the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. Alcohol might also affect IGF-binding protein-1 (IGFBP-1), which is an acute inhibitor of IGF-I. We studied how alcohol withdrawal affects Lp(a) levels and the GH/IGF-I/IGFBP-1 axis. Male alcohol abusers (n=27; 20 to 64 years old) were monitored immediately after alcohol withdrawal for 4 days. Twenty-six healthy men, mainly moderate drinkers, served as control subjects. Fasting blood samples were drawn to determine Lp(a), IGF-I, and IGFBP-1 (by ELISA, RIA, and immunoenzymometric assay, respectively). Nocturnal (12 hours) urine collection was performed in 9 alcoholics and 11 control subjects for GH analyses (RIA). The groups were similar in age and body mass index. Lp(a), GH, and IGF-I tended to be lower and IGFBP-1 higher in the alcoholics immediately after alcohol withdrawal than in the control subjects. During the 4-day observation in alcoholics, Lp(a) levels increased by 64% and IGF-I levels by 41%, whereas IGFBP-1 levels decreased by 59% (P<.001 after ANOVA for all comparisons). Urinary GH levels tended to decline. The increase in Lp(a) correlated inversely with the changes in IGFBP-1 (r= -.63, P<.001, n=27) and GH (r=-.70, P<.05, n=9), but not with IGF-I. In multiple regression analysis, the main predictors for the increase in Lp(a) were IGFBP-1 and urinary GH. In conclusion, alcohol withdrawal induces interrelated and potentially atherogenic changes in Lp(a) and IGFBP-1 levels.

Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study.

OBJECTIVE: To determine the association between features of the insulin resistance syndrome and Alzheimer's disease. 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 features of the insulin resistance syndrome and diagnosis of Alzheimer's disease by detailed neurological and neuropsychological evaluation. RESULTS: 46 (4.7%) subjects were classified as having probable or possible Alzheimer's disease. In univariate analyses, apolipoprotein E4 phenotype (odds ratio; 95% confidence interval 3.24: 1.77 to 5.92), age (1.16; 1.05 to 1.29), low level of education (0.82; 0.72 to 0.93), low total cholesterol concentration (0.77; 0.59 to 1.00), high systolic blood pressure (1.01; 1.00 to 1.03), high fasting and 2 hour plasma glucose concentrations (1.11; 1.01 to 1.23 and 1.08; 1.03 to 1.13, respectively), high fasting and 2 hour insulin concentrations (1.05; 1.02 to 1.08 and 1.003; 1.00 to 1.01, respectively), and abnormal glucose tolerance (1.86; 1.23 to 2.80) were significantly associated with Alzheimer's disease. In multivariate analysis including apolipoprotein E4 phenotype, age, education, systolic blood pressure, total cholesterol concentration, fasting glucose concentration, and insulin concentration, apolipoprotein E4 phenotype, age, education, total cholesterol, and insulin were significantly associated with Alzheimer's disease. In 532 non-diabetic subjects without the e4 allele hyperinsulinaemia was associated with an increased risk for Alzheimer's disease (prevalence of disease 7.5% v 1.4% in normoinsulinaemic subjects, P = 0.0004). In contrast, in the 228 with the e4 allele hyperinsulinaemia had no effect on the risk of disease (7.0% v 7.1%, respectively). CONCLUSION: Features of the insulin resistance syndrome are associated with Alzheimer's disease independently of apolipoprotein E4 phenotype.