Serum Concentrations of 25-Hydroxyvitamin D and Depression in a General Middle-Aged to Elderly Population in Finland.

OBJECTIVES: Low concentrations of serum 25-hydroxyvitamin D [25(OH)D] have been postulated to associate with an increased prevalence of depression. As there are a limited number of publications on this issue, we examined the association between serum 25(OH)D and depression in a general middle-aged or older population. DESIGN: A population-based cross-sectional study. SETTING AND PARTICIPANTS: A total of 1602 men and women from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in Eastern Finland, aged 53-73 y in 1998-2001, were analysed. MEASUREMENTS: Depressive symptoms were assessed with the DSM-III depression scale, and those individuals who had scores over 4 (range 0-12) or had reported undergoing current antidepressant therapy, were considered as suffering from depression. Associations were estimated in serum 25(OH)D tertiles using logistic regression. RESULTS: Among the participants, 183 subjects (11.4%) were considered to have depression. The mean age of the subjects was 62.6 years (SD 6.4, range 53.4-73.8 years). The mean serum 25(OH)D concentration was 43.8 nmol/L (SD 17.7, range 8.5-112.8 nmol/L), concentrations <50 nmol/L were observed in 65.0% of the subjects, and only 5.0% displayed concentrations ≥75 nmol/L. After multivariable adjustments, the odds ratios for having depression in the tertiles (from highest to the lowest) of serum 25(OH)D were 1, 1.35 (95 % CI: 0.87, 2.09) and 1.64 (95 % CI: 1.03, 2.59), P for trend=0.036. CONCLUSION: These findings indicate that a lower concentration of serum 25(OH)D is associated with a higher prevalence of depression in an elderly general population.

The joint impact of prediagnostic inflammatory markers and cardiorespiratory fitness on the risk of cancer mortality.

Independently, cardiorespiratory fitness (CRF), C-reactive protein (CRP), and leukocyte count have been shown to predict cancer death. Little is known about the joint impact of CRF and prediagnostic markers of inflammation, particularly leukocyte count and CRP, and their prognostic value with cancer death. The aim of this study was to explore the association between prediagnostic inflammatory markers and CRF with cancer mortality. A population-based cohort of 2270 men from Eastern Finland with no cancer history at baseline participated in the study. CRP, leukocyte count, and CRF data were among the measures collected at baseline. Blood leukocyte count was measured with a cell counter, and serum CRP concentrations were measured using an immunometric assay. The highest value or plateau of directly measured oxygen consumption by a respiratory gas analyzer during an incremental exercise test to exhaustion was used to describe CRF. Over an average follow-up of 22 years, 272 cases of cancer mortality occurred. In a multivariate model, the joint impact of high leukocyte count (>5.40 × 109 /L) and low CRF (VO2 max < 30.08 mL kg-1  min-1 ) had a 1.85-fold (95% CI 1.30-2.63, P < .01) increased risk for cancer death compared to men with low leukocyte count (<5.40 × 109 /L) and high CRF (VO2 max > 30.08 mL kg-1  min-1 ). The joint impact of CRP and CRF shared no association with cancer mortality in a multivariate model. The joint impact of high leukocyte count and low CRF increases risk for cancer death, suggesting it is a better predictor of cancer death compared to the joint impact of CRP and CRF.

Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase activities and incident metabolic syndrome.

BACKGROUND: The associations of n-6 polyunsaturated fatty acids (PUFA) with metabolic syndrome have been poorly explored. We investigated the associations of the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism, delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident metabolic syndrome. We also investigated whether zinc, a cofactor for these enzymes, modifies these associations. METHODS: A prospective follow-up study was conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and who were re-examined in 1998-2001. RESULTS: Men in the highest versus the lowest serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.18-0.51, Ptrend < 0.001]. Inverse associations were also observed for linoleic acid, arachidonic acid and D5D activity. By contrast, men in the highest tertile of D6D activity had an 84% higher risk (OR = 1.84; 95% CI = 1.15-2.94, Ptrend = 0.008). Similar associations were observed with many of the metabolic syndrome components at the re-examinations. Most associations were attenuated after adjustment for body mass index. Finally, the associations of D6D and LA were stronger among those with a higher serum zinc concentration. CONCLUSIONS: Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations and D5D activity were associated with a lower risk of developing metabolic syndrome and higher D6D activity was associated with a higher risk. The role of zinc also needs to be investigated in other populations.

Hepatitis C and risk of coronary atherosclerosis - A systematic review.

BACKGROUND: Observational studies on the association of chronic hepatitis C with coronary atherosclerosis have shown varying results and previous related reviews have been inconclusive. By careful outcome classification and further data syntheses, we aimed to clarify current evidence on the association between hepatitis C infection and coronary atherosclerosis. METHODS: Through systematic searches of PubMed and Scopus, related published observational studies were identified. These were narrowed by review of abstract, full review and quality assessment to yield eligible studies. These were used in qualitative and quantitative syntheses. RESULTS: The initial search identified 274 unique publications, which were narrowed to 15 by means of preliminary reviews, and narrowed further to 10 by quality assessment. The endpoints assessed varied, representing different attributes of the disease. The 10 studies were used in the subsequent meta-analyses. The risk of a person with chronic hepatitis C developing coronary atherosclerosis is about triple the risk in uninfected persons (OR = 3.06, 95% CI = 1.99-4.72). Coronary atherosclerosis in persons with chronic hepatitis C is also more severe. The pooled risk of coronary atherosclerosis-related events in persons with chronic hepatitis C was null (OR = 1.10 95% CI = 0.80-1.52). CONCLUSION: The current evidence indicates that hepatitis C virus or factors associated with HCV infection are apparently associated with increased risk of occurrence of coronary atherosclerosis and probably, increased severity of coronary atherosclerosis. Evidence of association with coronary atherosclerosis-related events is yet indeterminate.

Association between serum long-chain omega-3 polyunsaturated fatty acids and cognitive performance in elderly men and women: The Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND/OBJECTIVES: Fish intake and the long-chain omega-3 polyunsaturated fatty acids (PUFAs) in fish have been suggested to lower the risk of cognitive decline. We assessed whether serum long-chain omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are associated with performance on neuropsychological tests in an older population and whether exposure to methylmercury, mainly from fish, or apolipoprotein-E4 (Apo-E4) phenotype can modify the associations. SUBJECTS/METHODS: A total of 768 participants from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study were included. Cognitive function was measured using five neuropsychological tests: the Trail Making Test, the Verbal Fluency Test, the Selective Reminding Test, the Visual Reproduction Test and the Mini Mental State Exam. Multivariate-adjusted analysis of covariance and linear regression were used to analyze the cross-sectional associations. RESULTS: We found statistically significant associations between serum EPA+DPA+DHA and better performance in the Trail Making Test and the Verbal Fluency Test. The individual associations with EPA and DHA were similar with the findings with EPA+DPA+DHA, although the associations with DHA were stronger. No associations were observed with serum DPA. Pubic hair mercury content was associated only with a worse performance in the Trail Making Test, and mercury had only little impact on the associations between the serum PUFAs and cognitive performance. Apo-E4 phenotype did not modify the associations with PUFAs or mercury. CONCLUSIONS: Higher serum long-chain omega-3 PUFA concentrations were associated with better performance on neuropsychological tests of frontal lobe functioning in older men and women. Mercury exposure or Apo-E4 phenotype had little impact on cognitive performance.

Associations of serum n-3 and n-6 polyunsaturated fatty acids with plasma natriuretic peptides.

BACKGROUND/OBJECTIVES: The n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been associated with lower risk of cardiovascular disease (CVD), but little is known about their association with natriuretic peptides (NPs), a marker for CVD risk. The aim of this study was to investigate the association of serum n-3 and n-6 PUFAs with NPs. SUBJECTS/METHODS: A cross-sectional analysis of the association between serum n-3 and n-6 PUFAs with plasma N-terminal atrial (NT-proANP) and brain (NT-proBNP) NPs in a population-based sample of 985 men aged 46-65 years from Eastern Finland. RESULTS: After adjustment for age and examination year, only serum n-6 PUFA arachidonic acid (ARA) was inversely associated with NT-proANP (P-trend across quartiles=0.02), but further adjustments for conventional risk factors (body mass index, smoking, alcohol intake, systolic blood pressure, low-density lipoprotein cholesterol and history of CVD) attenuated the association (P-trend=0.10). The associations with the other PUFAs were not statistically significant. Among the PUFAs, only serum n-3 PUFA docosapentaenoic acid (DPA; P-trend=0.03) and ARA (P-trend=0.02) had inverse associations with NT-proBNP after adjustment for age and examination years. The associations were again attenuated after further adjustments but remained statistically significant for DPA (P-trend=0.05). Our results also suggested that the inverse associations may be more evident among those using beta-blockers. CONCLUSIONS: Our study suggests little overall impact of serum n-3 or n-6 PUFAs on plasma NPs.

Ca(2+) -activated K(+) current is essential for maintaining excitability and gene transcription in early embryonic cardiomyocytes.

AIM: Activity of early embryonic cardiomyocytes relies on spontaneous Ca(2+) oscillations that are induced by interplay between sarcoplasmic reticulum (SR) - Ca(2+) release and ion currents of the plasma membrane. In a variety of cell types, Ca(2+) -activated K(+) current (IK(Ca) ) serves as a link between Ca(2+) signals and membrane voltage. This study aimed to determine the role of IK (Ca) in developing cardiomyocytes. METHODS: Ion currents and membrane voltage of embryonic (E9-11) mouse cardiomyocytes were measured by patch clamp; [Ca(2+) ]i signals by confocal microscopy. Transcription of specific genes was measured with RT-qPCR and Ca(2+) -dependent transcriptional activity using NFAT-luciferase assay. Myocyte structure was assessed with antibody labelling and confocal microscopy. RESULTS: E9-11 cardiomyocytes express small conductance (SK) channel subunits SK2 and SK3 and have a functional apamin-sensitive K(+) current, which is also sensitive to changes in cytosolic [Ca(2+) ]i . In spontaneously active cardiomyocytes, inhibition of IK (Ca) changed action and resting potentials, reduced SR Ca(2+) load and suppressed the amplitude and the frequency of spontaneously evoked Ca(2+) oscillations. Apamin caused dose-dependent suppression of NFAT-luciferase reporter activity, induced downregulation of a pattern of genes vital for cardiomyocyte development and triggered changes in the myocyte morphology. CONCLUSION: The results show that apamin-sensitive IK (Ca) is required for maintaining excitability and activity of the developing cardiomyocytes as well as having a fundamental role in promoting Ca(2+) - dependent gene expression.

Serum long-chain omega-3 polyunsaturated Fatty acids and future blood pressure in an ageing population.

OBJECTIVES: To investigate the associations of serum long-chain omega-3 polyunsaturated fatty acids (PUFA) and hair mercury with future blood pressure in an ageing population. DESIGN: Prospective study with baseline measurements in 1998-2001 and follow-up measurements in 2005-2008. The linear relationships (ß) of baseline serum fatty acids and hair mercury with future systolic and diastolic blood pressure and pulse pressure were analyzed with multiple linear regression models, using log-transformed values. PARTICIPANTS: 181 men and 200 women aged 53-73 y from the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) population in Eastern Finland, who were free of cardiovascular disease, diabetes or hypertension at baseline. MEASUREMENTS: Total serum esterified and nonesterified fatty acids and pubic hair mercury were used as markers for exposure. Anthropometric and other lifestyle and health-related data were collected. RESULTS: The mean serum concentrations were 1.67% (SD 0.92) for eicosapentaenoic acid (EPA), 0.79% (SD 0.16) for docosapentaenoic acid (DPA) and 2.78 (SD 0.92) for docosahexaenoic acid (DHA), of all serum fatty acids. The mean hair mercury concentration was 1.5 µg/g (SD 1.6). We did not find statistically significant associations between the baseline serum long-chain omega-3 PUFA concentrations or hair mercury content and future blood pressure. Hair mercury did not modify the associations with the long-chain omega-3 PUFAs, either. CONCLUSIONS: Higher serum long-chain omega-3 PUFA concentration, a biomarker of fish or fish oil consumption, may not have an impact on future blood pressure in an ageing population.

Association of serum n-3 polyunsaturated fatty acids with C-reactive protein in men.

BACKGROUND/OBJECTIVES: N-3 polyunsaturated fatty acids (PUFAs) have been associated with reduced inflammation. We tested the hypothesis that high serum concentrations of the n-3 PUFAs are associated with lower serum C-reactive protein (CRP) concentrations in healthy middle-aged Finnish men. We also examined whether exposure to mercury, an environmental contaminant in fish, which is also a major source of long-chain n-3 PUFA, was associated with CRP. SUBJECTS/METHODS: Data from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study were analyzed cross-sectionally to determine the associations between serum n-3 PUFAs, hair mercury and serum CRP in 1395 healthy men, aged 42-60 years. Linear regression analyses were performed to analyze the associations. RESULTS: In the multivariate models, the mean serum CRP in quartiles of serum total n-3 PUFA concentration was 1.23, 1.27, 1.18 and 1.08 mg/l, P for trend = 0.01. Statistically significant inverse associations were also observed with the total serum long-chain n-3 PUFA concentration and with the individual long-chain n-3 PUFAs docosapentaenoic acid and docosahexaenoic acid, but not with eicosapentaenoic acid or with the intermediate-chain n-3 PUFA alpha-linolenic acid. Hair methylmercury content was not associated with serum CRP levels and it did not modify the associations between serum n-3 PUFAs and CRP either. CONCLUSIONS: Serum n-3 PUFAs and especially the long-chain n-3 PUFA concentration, a marker of fish or fish oil consumption, were inversely associated with serum CRP in men. Exposure to mercury was not associated with serum CRP.

Two-minute heart rate recovery after cycle ergometer exercise and all-cause mortality in middle-aged men.

BACKGROUND: A slow heart rate recovery (HRR) after an exercise test is associated with an increased risk of all-cause mortality in asymptomatic individuals, but the data regarding additional prognostic information provided by HRR beyond other exercise test variables are inconsistent. We investigated the prognostic significance of HRR for premature death, particularly in relation to other exercise test variables. METHODS: The study subjects were a representative population-based sample of 1102 men (42-61 years of age) without cardiovascular disease, cancer or diabetes. HRR was defined as the difference between maximal HR and HR 2 min after a maximal symptom-limited exercise test using a cycle ergometer. The association between HRR and premature mortality was examined with Cox regression models. RESULTS: During an average follow-up of 18 years, 238 deaths occurred. HRR was an independent predictor of death [for a decrease of 12 beats min(-1) , relative risk (RR) 1.16, 95% CI 1.02-1.33, P = 0.02] after adjustment for age and established risk factors. When added in a Cox model with chronotropic response (decrease of 12 beats min(-1) , RR 1.09, 95% CI 0.93-1.27, P = 0.26) or cardiorespiratory fitness (decrease of 12 beats min(-1) , RR 1.12, 95% CI 0.98-1.30, P = 0.08), the association between a slow HRR and an increased risk of death was clearly weaker. CONCLUSION: A slow 2-min HRR after a cycle ergometer exercise test was an independent predictor of death in healthy middle-aged men after accounting for demographic and clinical characteristics. However, it was no longer predictive after accounting for chronotropic response and exercise capacity.

Glycemic index, glycemic load, and the risk of acute myocardial infarction in Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND AND AIM: The role of dietary glycemic index (GI) and glycemic load (GL) in coronary heart disease (CHD) is unclear. Our aim was to study the association between the dietary GI and GL and the risk of acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 1981 Finnish men from the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study, aged 42-60 years and free of CHD at baseline. During an average follow-up time of 16.1 years, 376 new AMI events occurred. In multivariable-adjusted Cox proportional hazards models, the relative risk (RR) for AMI in the highest quartile of GI was 1.25 (95% CI: 0.92-1.69; P for trend=0.08) and for GL 1.11 (95% CI: 0.79-1.57; P for trend=0.21) when compared with the lowest quartile. For overweight (BMI ≥ 27.5 kg/m²) men, the multivariable-adjusted RR for AMI in the highest compared to the lowest tertile of GI and GL were 1.58 (95% CI: 1.03-2.43; P for trend=0.04, P for interaction=0.01) and 2.05 (95% CI: 1.30-3.23; P for trend=0.002, P for interaction=0.002), respectively. For physically less active men; energy expenditure for leisure-time physical activity < 50 kcal/d, the RR for AMI was 1.72 (95% CI: 1.07-2.76; P for trend=0.04, P for interaction 0.80) with higher GL. CONCLUSIONS: Our results suggest that both high dietary GI and GL are associated with increased risk of AMI among overweight and GL possibly among less physically active men.

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohorts

Cardiac power during exercise and the risk of stroke in men.

BACKGROUND AND PURPOSE: Low maximal oxygen uptake (VO2max) has been shown to predict the risk of stroke. However, VO2max does not take into account the differences in cardiac afterload between subjects. The aim of this study was to examine the relationship of exercise cardiac power (ECP), defined as a ratio of VO2max with peak systolic blood pressure (SBP) during exercise, with the risk for stroke. METHODS: Population-based cohort study with an average follow-up of 12 years from eastern Finland. A total of 1761 men with no history of stroke or coronary heart disease at baseline participated. Among these men, 91 strokes occurred, of which 69 were attributable to ischemic causes. RESULTS: The relative risk of any stroke in men with low ECP (<10.3 mL/mm Hg) was 2.7 (95% CI, 1.2 to 6.0; P=0.01; P=0.02 for the trend across the quartiles), and the relative risk for ischemic stroke was 2.7 (95% CI, 1.1 to 7.0; P=0.03; P=0.04 for trend across the quartiles) compared with men having high ECP (>14.3 mL/mm Hg) during exercise after adjusting for age, examination year, cigarette smoking, alcohol consumption, body mass index, diabetes, serum total cholesterol level, energy expenditure of physical activity, exercise-induced myocardial ischemia, and the use of antihypertensive medication. After further adjustment for resting SBP, results were statistically nonsignificant. CONCLUSIONS: Low ECP provides noninvasive and easily available measure for stroke risk. One of the most potential explanations for the association between ECP and the increased risk of stroke is an elevated afterload and peripheral resistance indicated by elevated SBP.

C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men.

AIMS/HYPOTHESIS: Low-grade inflammation has been implicated in the development of Type 2 diabetes and cardiovascular disease, but its role in the pathogenesis of the metabolic syndrome is unclear. We investigated the association between C-reactive protein (CRP) levels and the development of the metabolic syndrome and diabetes in men. METHODS: Serum CRP concentrations and factors related to insulin resistance were determined in middle-aged Finnish men who participated in a population-based cohort study and were free of diabetes at baseline. RESULTS: At the 11-year follow-up, 143 of 680 men had developed the metabolic syndrome as defined by the National Cholesterol Education Program (NCEP) and 103 of 598 men had developed the metabolic syndrome as defined by the World Health Organization (WHO). Our analyses excluded men with the metabolic syndrome by the respective definition at baseline. In all, 78 of 762 men developed diabetes over the same period. Men with CRP concentrations > or =3 mg/l had a several-fold higher age-adjusted risk of developing the metabolic syndrome (NCEP definition: odds ratio [OR]=3.2, 95% CI 1.9-5.5; WHO definition: OR=3.4, 95% CI 2.0-6.1) or diabetes (OR=4.1, 95% CI 2.1-8.0) than men whose CRP levels were <1.0 mg/l. Even after further adjustment for potentially confounding lifestyle factors and factors related to insulin resistance, the risk of diabetes (OR=2.3, 95% CI 1.0-5.1) was still increased in men with CRP concentrations > or =3 mg/l, but the association with the metabolic syndrome was no longer significant. CONCLUSIONS/INTERPRETATION: Low-grade inflammation may increase the risk of the metabolic syndrome and diabetes in middle-aged men, but some of the risk is mediated through obesity and factors related to insulin resistance.

C18 hydroxy fatty acids as markers of lipid peroxidation ex vivo and in vivo.

Different C18 monohydroxy fatty acids (OHFAs) were evaluated for their usefulness as markers of plasma lipid peroxidation (unsaturated fatty acid oxidation) ex vivo and in vivo. First, plasma samples (n = 5) were exposed for 3 h to different radical fluxes ex vivo. The formation of OHFAs was assessed by using varying concentrations of Cu2+ ions and AAPH (2,2'-azobis(2-amidinopropane) hydrochloride) as radical flux initiators. Secondly, a cross-sectional study was carried out in 47 middle-aged men. In this study, plasma concentrations of different in vivo OHFAs were compared with other indices of lipid peroxidation. Under mild oxidation conditions (heparin plasma containing 4.2 or 8.3 mM AAPH), concentrations of all the measured OHFAs (8, 9, 10, 11, 12, 13, 15 and 16-OH acids) increased in an identical manner, but under highly oxidative conditions (heparin plasma containing 83 mM AAPH or 4.2 to 8.3 mM CuSO4) mainly 9 and 13-OHFAs were formed. In the cross-sectional study, plasma 11 and 13-OHFA levels were associated statistically significantly with plasma free F2alpha-isoprostanes, recognized index of in vivo lipid peroxidation (r = 0.305, p = 0.037 and r = 0.308, p = 0.035, respectively). In addition, 16-OHFA levels correlated with the ratio of electronegatively charged LDL to total LDL (r = 0.335, p = 0.021). With respect to the other OHFAs, 15-OHFA had no correlation with either other OHFAs or the reference substances used. In addition, occasionally there were contamination problems in the assessment of 12-OHFA. It is concluded that all of the measured C18 OHFAs can be used as indicators of plasma lipid peroxidation under mild oxidation conditions, though the 12 and 15-OHFAs may need to be used with some caution. Under high oxidation conditions, 9-and 13-OHFAs seem to be the most useful indices because of their high formation capacity.

Association of exercise-induced, silent ST-segment depression with the risk of stroke and cardiovascular diseases in men.

BACKGROUND AND PURPOSE: There are few if any data on the prognostic importance of silent myocardial ischemia during exercise with regard to the risk of stroke and cardiovascular diseases (CVDs) among asymptomatic men. In this prospective study, we investigated the relation of silent myocardial ischemia and the risk of stroke and CVD death in men with and without conventional risk factors. METHODS: The study sample included 1726 middle-aged men with no history of stroke, coronary heart disease, or atrial fibrillation at baseline. Silent myocardial ischemia was defined as a horizontal or downsloping ST-segment depression (>or=1 mm) during exercise electrocardiography. A total of 86 CVD-related deaths and 78 strokes occurred during an average follow-up of 10 years. RESULTS: Men with silent ischemia during exercise had a 3.5-fold increased risk of CVD death and a 2.2-fold increased risk of stroke compared with men without silent ischemia, after adjusting for conventional risk factors. Silent ischemia during exercise was associated with a 3.8-fold (95% confidence interval [CI], 1.5 to 9.5) increased risk for CVD in smokers, a 3.9-fold (95% CI, 2.1 to 7.3) increased risk in hypercholesterolemic subjects, a 3.6-fold (95% CI, 1.9 to 6.8) increased risk in the hypertensives, and 3.8-fold (95% CI, 2.0 to 7.1) increased risk in overweight men. The respective relative risks for stroke were 3.8 (95% CI, 1.1 to 12.5), 3.5 (95% CI, 1.7 to 7.4), 3.4 (95% CI, 1.6 to 7.1), and 2.9 (95% CI, 1.4 to 6.1). CONCLUSIONS: Exercise-induced silent myocardial ischemia is an important indicator of increased risk of stroke and CVD in men with other risk factors, such as smoking, hypercholesterolemia, hypertension, and being overweight.

Plasma vitamin C modifies the association between hypertension and risk of stroke.

BACKGROUND AND PURPOSE: There are no prospective studies to determine whether plasma vitamin C modifies the risk of stroke among hypertensive and overweight individuals. We sought to examine whether plasma vitamin C modifies the association between overweight and hypertension and the risk of stroke in middle-aged men from eastern Finland. METHODS: We conducted a 10.4-year prospective population-based cohort study of 2419 randomly selected middle-aged men (42 to 60 years) with no history of stroke at baseline examination. A total of 120 men developed a stroke, of which 96 were ischemic and 24 hemorrhagic strokes. RESULTS: Men with the lowest levels of plasma vitamin C (<28.4 micromol/L, lowest quarter) had a 2.4-fold (95% CI, 1.4 to 4.3; P=0.002) risk of any stroke compared with men with highest levels of plasma vitamin C (>64.96 micromol/L, highest quarter) after adjustment for age and examination months. An additional adjustment for body mass index, systolic blood pressure, smoking, alcohol consumption, serum total cholesterol, diabetes, and exercise-induced myocardial ischemia attenuated the association marginally (relative risk, 2.1; 95% CI, 1.2 to 3.8; P=0.01). Adjustment for prevalent coronary heart disease and atrial fibrillation did not attenuate the association any further. Furthermore, hypertensive men with the lowest vitamin C levels (<28.4 micromol/L) had a 2.6-fold risk (95% CI, 1.52 to 4.48; P<0.001), and overweight men (> or =25 kg/m2) with low plasma vitamin C had a 2.7-fold risk (95% CI, 1.48 to 4.90; P=0.001) for any stroke after adjustment for age, examination months, and other risk factors. CONCLUSIONS: Low plasma vitamin C was associated with increased risk of stroke, especially among hypertensive and overweight men.

Exhaustive exercise increases plasma/serum total oxidation resistance in moderately trained men and women, whereas their VLDL + LDL lipoprotein fraction is more susceptible to oxidation.

The purpose of this study was to evaluate the effects of exhaustive exercise (marathon run) on different lipid peroxidation measurements, including copper-induced serum lipids and VLDL + LDL oxidation susceptibility, and on plasma total antioxidative capacity (TRAP), muscular damage and plasma antioxidants in healthy moderately trained male (n = 21) and female (n = 25) volunteers. Blood samples were taken before and just after the 42-km run. In women, baseline levels of several antioxidative compounds (serum albumin and uric acid, plasma free thiols and blood glutathione) were lower, resulting in 21.5% lower plasma total antioxidative capacity and 70.3% higher serum oxidation susceptibility, compared to men. To compare effects in men and women, the exercise-induced variable changes were adjusted for their baseline levels. After this adjustment, there were no statistically significant differences between the genders in the extent of muscular damage (serum creatine kinase, (CK)), or in the change in serum lipids or VLDL + LDL oxidation susceptibility, or that of plasma antioxidative capacity. A possible beneficial effect of exercise was that serum HDL cholesterol levels increased significantly in both genders, but especially in women. In the group of pooled genders (n=46), the increases in serum CK and in plasma lactate were 190% (95% CI, 133% to 246%) and 109% (95% CI, 65% to 175%), respectively. On the basis of our lipid peroxidation and TRAP measurements, uric acid was observed to be the most important plasma antioxidant. The effect of exercise was to decrease the oxidation susceptibility of serum lipids by 24.8% (95% CI 13.4% to 36.2%) and to elevate plasma TRAP by 14.6% (95% CI, 11.4% to 17.7%). Nonetheless, the oxidation susceptibility of the VLDL + LDL fraction increased by 11.0% (95% CI, 1.9% to 20.2%). Our results suggest that there are no gender-based differences in exhaustive exercise-induced lipid peroxidation or muscular damage. Secondly, even though exhaustive exercise can increase plasma/serum total resistance towards oxidation, the oxidation resistance of the atherogenic lipoprotein fraction might be diminished. On the basis of these results, several in vitro measurements of lipid peroxidation assessing both water and lipid soluble plasma fractions are needed if a true perspective of the plasma redox status is to be obtained.

Leucine7 to proline7 polymorphism in the preproneuropeptide Y is associated with the progression of carotid atherosclerosis, blood pressure and serum lipids in Finnish men.

A rather common leucine7-to-proline7 (Leu7Pro) polymorphism in the preproneuropeptide Y (prepro-NPY) gene signal peptide may be important in blood pressure regulation, cholesterol metabolism and the pathogenesis of atherosclerosis in humans. We examined the associations of the Leu7Pro polymorphism with carotid atherosclerotic progression, blood pressure and serum lipids in a population-based sample of 966 men aged 42-60 years in Finland. The Pro7 substitution (carrier frequency 12.2%) was associated with accelerated four-year increase in the mean (P=0.01) and maximal (P=0.007) common carotid intima-media thickness (IMT) and with slightly increased systolic (P=0.03) and diastolic (P=0.02) blood pressures, adjusted for other major risk factors. Men with Pro7 substitution had 30.6% (95% CI 6.9-54.0%) greater increase in the mean IMT and 20.0% (95% CI 5.3-34.4%) greater increase in the maximal IMT than men with Leu7/Leu7 genotype. The Pro7 substitution was also related to increased serum total cholesterol (P=0.01) and LDL cholesterol (P=0.02) in obese (body mass index (BMI)>30 kg/m(2)) men. This study provides important evidence suggesting that the Pro7 substitution in the prepro-NPY is an important risk factor for accelerated atherosclerotic progression, increased blood pressure and increased serum cholesterol in humans.