Biomedical subjects

J T Salonen

Publications and source records attributed to J T Salonen.

At least 37 records · Page 2Linked to original sources

PubMed2002

Abdominal obesity is associated with increased risk of acute coronary events in men.

AIMS: The purpose of the study was to investigate the associations of abdominal obesity and overall obesity with the risk of acute coronary events. METHODS AND RESULTS: Body mass index indicating overall obesity and waist-to-hip ratio and waist circumference indicating abdominal obesity were measured for 1346 Finnish men aged 42-60 years who had neither cardiovascular disease nor cancer at baseline. There were 123 acute coronary events during an average follow-up of 10.6 years. In Cox regression analyses adjusted for confounding factors, waist-to-hip ratio (P=0.009), waist circumference (P=0.010) and body mass index (P=0.013) as continuous variables were associated directly with the risk of coronary events. These associations were in part explained by blood pressure, diabetes, fasting serum insulin, serum lipids, plasma fibrinogen, and serum uric acid. Waist-to-hip ratio of > or =0.91 was associated with a nearly threefold risk of coronary events. Waist-to-hip ratio provided additional information beyond body mass index in predicting coronary heart disease, whereas body mass index did not add to the predictive value of waist-to-hip ratio. Abdominal obesity combined with smoking and poor cardiorespiratory fitness increased the risk of coronary events 5.5 and 5.1 times, respectively. CONCLUSIONS: Abdominal obesity is an independent risk factor for coronary heart disease in middle-aged men and even more important than overall obesity. Since the effect of abdominal obesity was strongest in smoking and unfit men, the strategy for lifestyle modification to prevent coronary heart disease should address these issues jointly.

Abdomen↗

PubMed2002

Obesity and weight gain are associated with increased incidence of hyperinsulinemia in non-diabetic men.

We investigated the temporal relationships between obesity, weight change and hyperinsulinemia in a population-based 4-year follow-up study of 695 middle-aged, non-diabetic, and normoinsulinemic men. Thirty-eight men developed hyperinsulinemia during the follow-up (fasting serum insulin > or = 12.0 mU/l). In logistic regression analysis adjusting for other risk factors, men with body mass index of > or = 26.7 kg/m2 (highest third) had a 6.6-fold (p = 0.001) risk of developing hyperinsulinemia, compared with men with body mass index of < 24.4 kg/m2 (lowest third). Correspondingly, men with waist-to-hip ratio of > or = 0.95 (highest third) had a 3.5-fold (p = 0.028) incidence of hyperinsulinemia compared with men with waist-to-hip ratio of < 0.90 (lowest third). Weight gain in middle age and weight gain from the age of 20 years to middle age were also associated with increased risk of hyperinsulinemia. Hyperinsulinemia at baseline was not associated with weight gain during the follow-up. This prospective population-based study emphasizes the importance of avoiding obesity and weight gain during adulthood in preventing hyperinsulinemia.

Adult↗

PubMed2002

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.

Adult↗

PubMed2002

Level of fibrinogen and risk of fatal and non-fatal stroke. EUROSTROKE: a collaborative study among research centres in Europe.

BACKGROUND: It is well established that raised levels of fibrinogen increase the risk of coronary heart disease. For stroke, however, data are much more limited and restricted to overall stroke. This study investigated the association between fibrinogen and fatal, non-fatal, haemorrhagic and ischaemic stroke in three European cohorts participating in EUROSTROKE. METHODS: EUROSTROKE is a collaborative project among ongoing European cohort studies on incidence and risk factors of stroke. EUROSTROKE is designed as a nested case-control study. For each stroke case, two controls were sampled. Strokes were classified according to MONICA criteria or reviewed by a panel of four neurologists. Recently, data on stroke and fibrinogen became available from cohorts in Cardiff (79 cases/194 controls), Kuopio (74/124), and Rotterdam (62/203). Results were adjusted for age, sex, smoking, and systolic blood pressure. RESULTS: The risk of stroke gradually increased with increasing fibrinogen levels: the odds ratios per quartile increase were 1.08 (95% CI 0.63 to 1.84), 1.91 (1.12 to 3.26) and 2.78 (1.64 to 4.72), respectively. This association was similar for ischaemic (n=138) and haemorrhagic stroke (n=25). Associations between fibrinogen and stroke were similar across strata of smoking, diabetes mellitus, previous myocardial infarction, and HDL cholesterol. The odds ratio, however, tended to increase with increasing systolic blood pressure: from 1.21 among those with a systolic pressure <120 mm Hg to 1.99 among subjects with a systolic pressure of 160 mm Hg or above. CONCLUSION: This analysis of the EUROSTROKE project indicates that fibrinogen is a powerful predictor of stroke. Results did not disclose a differential in this relation of fibrinogen and fatal or non-fatal stroke, or with type of stroke (ischaemic or haemorrhagic).

Adult↗

PubMed2002

Total and HDL cholesterol and risk of stroke. EUROSTROKE: a collaborative study among research centres in Europe.

BACKGROUND: Controversy remains on the relation between serum lipids levels and stroke risk. This paper investigated the association of total and HDL cholesterol level to fatal and non-fatal, and haemorrhagic and ischaemic stroke in four European cohorts participating in EUROSTROKE. METHODS: EUROSTROKE is a collaborative project among ongoing European cohort studies on incidence and risk factors of stroke. EUROSTROKE is designed as a nested case-control study. For each stroke case, two controls were sampled. Strokes were classified according to MONICA criteria or reviewed by a panel of four neurologists. At present, data on stroke and risk factors were available from cohorts in Cardiff (84 cases), Kuopio (74 cases), Rotterdam (157 cases), and Novosibirsk (79 cases). RESULTS: Pooled analyses showed no significant association between total cholesterol and risk of stroke (odds ratio for increase of 1 mmol/l in cholesterol of 0.98 (95% CI 0.88 to 1.09)). Analyses for haemorrhagic stroke and cerebral infarction revealed odds ratios of 0.80 (95% CI 0.61 to 1.05) and 1.06 (95% CI 0.94 to 1.19), respectively. The association of HDL cholesterol to stroke was different in men compared with women. In men, there was a general trend towards a lower risk of stroke with an increase in HDL (odds ratio per 1 mmol/l increase in HDL cholesterol 0.68 (95% CI 0.40 to 1.16)). In women, however, an increase in HDL was associated with a significant increased risk of non-fatal stroke and of cerebral infarction (odds ratios of 2.46 (95% 0.1.20 to 5.04) and 2.52 (95% CI 1.15 to 5.50), respectively. The difference between men and women in the association of HDL with stroke seemed to differ mainly in smokers and never smokers, but not among ex smokers. CONCLUSION: This analysis of the EUROSTROKE project could not disclose an association of total cholesterol with fatal, non-fatal, haemorrhagic or ischaemic stroke. HDL cholesterol however, seemed to be related to stroke differently in men than in women.

Adult↗

PubMed2002

The EUROSTROKE cohorts: a short description and data analytical approach.

This paper describes the design and methodology of the participating cohorts in the EUROSTROKE project. Information is given about the cohort sampling, its size, the follow up procedures and event classification. Information is also given about the measurement of the cardiovascular and cerebrovascular risk factors in each of the cohorts separately. The cohorts described are the Caerphilly study in Cardiff, United Kingdom; the Kuopio Ischaemic Heart disease study in Kuopio, Finland; the Portugal study in Coimbra, Portugal; the EPIC cohort in Athens, Greece; the Ilsa study from Firenze, Italy; the Rotterdam Study in Rotterdam, the Netherlands, and the Novosibirsk cohort in Novosibirsk, Russia.

Adult↗

PubMed2002

Gamma-glutamyltransferase and risk of stroke: the EUROSTROKE project.

BACKGROUND: Alcohol consumption has been implicated in the aetiology of stroke. As data on alcohol consumption obtained by questionnaire are susceptible to misclassification, this study evaluated the association between gamma-glutamyltransferase (gamma-GT), as a marker for alcohol consumption, and fatal, non-fatal, haemorrhagic and ischaemic stroke in three European cohort studies, participating in EUROSTROKE. METHODS: EUROSTROKE is a collaborative project among ongoing European cohort studies on incidence and risk factors of stroke. EUROSTROKE is designed as a nested case-control study. For each stroke case, two controls were sampled. Strokes were classified according to MONICA criteria or reviewed by a panel of four neurologists. At present, data on stroke and gamma-GT were available from cohorts in Cardiff (57 cases), Kuopio (66 cases), and Rotterdam (108 cases). RESULTS: An increase in gamma-GT of one standard deviation (28.7 IU/ml) was associated with an age and sex adjusted 26% (95% CI 5 to 53) increase in risk of stroke. Adjustment for confounding variables such as drug use, history of myocardial infarction, total cholesterol, and diabetes mellitus did not materially attenuate the association. The risk of haemorrhagic stroke increased linearly with increase in gamma-GT. The association for cerebral infarction was not graded: the risk increased beyond the first quartile, and remained increased. The association of gamma-GT with stroke was significantly stronger among subjects without diabetes mellitus compared with subjects with diabetes mellitus (no association observed). CONCLUSION: This EUROSTROKE analysis showed that an increased gamma-GT, as a marker of alcohol consumption, is associated with increased risk of stroke, in particular haemorrhagic stroke.

Adult↗

PubMed2002

Prediction of stroke in the general population in Europe (EUROSTROKE): Is there a role for fibrinogen and electrocardiography?

BACKGROUND: To decide whether a person with certain characteristics should be given any kind of intervention to prevent a cardiovascular event, it would be helpful to classify subjects in low, medium and high risk categories. The study evaluated which well known cerebrovascular and cardiovascular correlates, in particular fibrinogen level and ECG characteristics, are able to predict the occurrence of stroke in men of the general population using data from three European cohorts participating in EUROSTROKE. METHODS: EUROSTROKE is a collaborative project among ongoing European population based cohort studies and designed as a prospective nested case-control study. For each stroke case two controls were sampled. Strokes were classified according to MONICA criteria or reviewed by a panel of four neurologists. Complete data were available of 698 men (219 stroke events) from cohorts in Cardiff (84 cases/200 controls), Kuopio (74/148) and Rotterdam (61/131). Multivariable logistic regression modeling was used to evaluate which information from history, physical examination (for example, blood pressure), blood lipids, and fibrinogen and ECG measurements independently contributed to the prediction of stroke. The area under receiver operating characteristic curve (ROC area) was used to estimate the predictive ability of models. RESULTS: Independent predictors from medical history and physical examination were age, stroke history, medically treated hypertension, smoking, diabetes mellitus and diastolic blood pressure. The ROC area of this model was 0.69. After validating and transforming this model to an easy applicable rule, 40% of all future stroke cases could be predicted. Adding pulse rate, body mass index, blood lipids, fibrinogen level and ECG parameters did not improve the classification of subjects in low, medium and high risk. Results were similar when fibrinogen was dichotomised at the upper tertile or quintile. CONCLUSION: In the general male population the future occurrence of stroke may be predicted using easy obtainable information from medical history and physical examination. Measurement of pulse rate, body mass index, blood lipids, fibrinogen level and ECG characteristics do not contribute to the risk stratification of stroke and have no value in the screening for stroke in the general male population.

Adult↗

PubMed2002

Left ventricular hypertrophy and risk of fatal and non-fatal stroke. EUROSTROKE: a collaborative study among research centres in Europe.

BACKGROUND: This study investigated the association between electrocardiographically assessed left ventricular hypertrophy (LVH) and fatal, non-fatal, haemorrhagic and ischaemic stroke in four European cohorts participating in EUROSTROKE. METHODS: EUROSTROKE is a collaborative project among ongoing European cohort studies to investigate differences in incidence of, and risk factors for, stroke between countries. EUROSTROKE is designed as a nested case-control study. For each stroke case, two controls were sampled. Strokes were classified according to MONICA criteria or reviewed by a panel of four neurologists. LVH was assessed according to the Minnesota code or the automated diagnostic MEANS classification system. For this analysis, data on LVH and stroke were available from cohorts in Cardiff (84 cases/200 controls), Kuopio (60/116), Rotterdam (114/334), and Novosibirsk (62/168). Results are adjusted for age and sex. RESULTS: LVH was associated with a twofold increased risk of stroke (odds ratio 2.1 (95% CI 1.3 to 3.5). The risk was particularly pronounced for fatal stroke (4.0 (95% CI 2.1 to 7.9)), whereas the risk was non-significantly increased for non-fatal stroke (1.5 (95% CI 0.8 to 2.7)). The increased risk was more pronounced in smokers: for total stroke 3.5 (95% CI 1.5 to 8.1) versus 1.6 (95% CI 0.8 to 3.1) in non-smokers. Adjustment for systolic blood pressure and body mass index attenuated the associations. LVH was not preferentially associated with a particular type of stroke, although the association with cerebral infarction was stronger. CONCLUSION: This analysis of the EUROSTROKE project indicates that LVH assessed by electrocardiogram is a predictor of stroke. The association seems to be stronger for fatal stroke than for non-fatal stroke and is more pronounced in smokers.

Adult↗

PubMed2002

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.

Adult↗

PubMed2001

Low dietary folate intake is associated with an excess incidence of acute coronary events: The Kuopio Ischemic Heart Disease Risk Factor Study.

BACKGROUND: Although several prospective studies have shown that low folate intake and low circulating folate are associated with increased risk of coronary heart disease (CHD), the findings are inconsistent. METHODS AND RESULTS: We studied the associations of dietary intake of folate, vitamin B(6), and vitamin B(12) with the risk of acute coronary events in a prospective cohort study of 1980 Finnish men 42 to 60 years old examined in 1984 to 1989 in the Kuopio Ischemic Heart Disease Risk Factor Study. Nutrient intakes were assessed by 4-day food record. During an average follow-up time of 10 years, 199 acute coronary events occurred. In a Cox proportional hazards model adjusted for 21 conventional and nutritional CHD risk factors, men in the highest fifth of folate intake had a relative risk of acute coronary events of 0.45 (95% CI 0.25 to 0.81, P=0.008) compared with men in the lowest fifth. This association was stronger in nonsmokers and light alcohol users than in smokers and alcohol users. A high dietary intake of vitamin B(6) had no significant association and that of vitamin B(12) a weak association with a reduced risk of acute coronary events. CONCLUSIONS: The present work in CHD-free middle-aged men is the first prospective cohort study to observe a significant inverse association between quantitatively assessed moderate-to-high folate intakes and incidence of acute coronary events in men. Our findings provide further support in favor of a role of folate in the promotion of good cardiovascular health.

Acute Disease↗

PubMed2001

Cardiovascular fitness as a predictor of mortality in men.

OBJECTIVE: To examine the relations of cardiorespiratory fitness, as measured by maximal oxygen uptake and exercise test duration at the initiation of the study, with overall, cardiovascular disease (CVD)-related, and non-CVD-related mortality. METHODS: A population-based cohort study of 1294 men with no CVD, pulmonary disease, or cancer at baseline in Kuopio and surrounding communities in eastern Finland. During an average follow-up of 10.7 years, there were 124 overall, 42 CVD-related, and 82 non-CVD-related deaths. RESULTS: The relative risk of overall death in unfit men (maximal oxygen uptake <27.6 mL/kg per minute) was 2.76 (95% confidence interval, 1.43-5.33) (P =.002), and the relative risk of CVD-related death was 3.09 (95% confidence interval, 1.10-9.56) (P =.05), compared with fit men (maximal oxygen uptake >37.1 mL/kg per minute) after adjusting for age, examination years, smoking, and alcohol consumption. The relative risk of non-CVD-related death in unfit men was almost the same magnitude as for overall death. Furthermore, adjustment for serum lipid levels, blood pressure, plasma fibrinogen level, diabetes, and fasting serum insulin level did not weaken these associations significantly. Exercise test duration also had a strong inverse relation to overall, CVD-related, and non-CVD-related mortality. Poor cardiorespiratory fitness was comparable with elevated systolic blood pressure, smoking, obesity, and diabetes in importance as a risk factor for mortality. CONCLUSIONS: Cardiorespiratory fitness had a strong, graded, inverse association with overall, CVD-related, and non-CVD-related mortality. Maximal oxygen uptake and exercise test duration represent the strongest predictors of mortality.

Adult↗

PubMed2001

Abdominal obesity is associated with accelerated progression of carotid atherosclerosis in men.

Abdominal obesity increases the risk of clinical atherosclerotic diseases, but whether it accelerates the progression of preclinical atherosclerosis is unknown. We studied whether waist-to-hip ratio (WHR) and waist circumference are associated with 4-year increase in indicators of common carotid atherosclerosis, assessed by B-mode ultrasonography, in 774 Finnish men aged 42-60 years without atherosclerotic diseases. Men with WHR of <0.91, 0.91-0.96 and >0.96 (thirds) had increase in maximal intima-media thickness (IMT) of 0.230, 0.255 and 0.281 mm/4 years (P=0.007 for linear trend; P=0.025 for difference) and plaque height of 0.241, 0.254 and 0.291 mm/4 years (P=0.005, P=0.013) adjusting for age, body mass index and technical covariates. Men with waist circumference of <85, 85-93 and >93 cm (thirds) had increase in maximal IMT of 0.227, 0.251 and 0.290 mm/4 years (P=0.011, P=0.035) and plaque height of 0.229, 0.263 and 0.296 mm/4 years (P=0.003, P=0.013). These associations were stronger in men with high (> or =3.8 mmol/l) than lower serum LDL cholesterol (P<0.05 for interaction). This is the first documentation that abdominal obesity is associated with accelerated progression of atherosclerosis, and supports the view that it is an important cardiovascular risk factor. This study emphasizes the role of avoiding abdominal obesity to prevent atherosclerotic diseases.

Abdomen↗

PubMed2001

Cardiorespiratory fitness and the progression of carotid atherosclerosis in middle-aged men.

BACKGROUND: Good cardiorespiratory fitness has been associated with reduced risk for clinical events of atherosclerotic vascular diseases, but whether it is related to slower progression of early atherosclerosis is unclear. OBJECTIVE: To study the association between cardiorespiratory fitness and the progression of early carotid atherosclerosis. DESIGN: 4-year follow-up study. SETTING: Eastem Finland. PARTICIPANTS: Population-based sample of 854 men 42 to 60 years of age. MEASUREMENTS: Maximal oxygen uptake (VO2max [mL/kg per minute]) was measured directly by using respiratory gas exchange in a cycle ergometer exercise test. Carotid atherosclerosis was assessed by using B-mode ultrasonography. RESULTS: After adjustments for age, technical covariates, and cigarette smoking, VO2max had strong, inverse, and graded associations with 4-year increases in maximal intima-media thickness (IMT) (standardized regression coefficient beta = -0.120; P = 0.002), plaque height (beta = -0.140; P < 0.001), surface roughness (beta = -0.147; P < 0.001), and mean IMT (beta = -0.080; P = 0.035). These associations weakened but remained statistically significant after additional adjustment for systolic blood pressure, serum levels of apolipoprotein B, diabetes, and plasma fibrinogen levels. The increases in maximal IMT, surface roughness, and mean IMT (23%, 31%, and 100%, respectively) were larger among men in the lowest quartile of VO2max (<26.1 mL/kg per minute) than among those in the highest quartile (>36.2 mL/kg per minute). CONCLUSIONS: Good cardiorespiratory fitness is associated with slower progression of early atherosclerosis in middle-aged men. These findings are important because they emphasize that middle-aged men can be evaluated for cardiorespiratory fitness to estimate their future risk for atherosclerotic vascular diseases. Additional research is warranted to investigate a possible causal relationship between cardiorespiratory fitness and atherosclerosis.

Adult↗

PubMed2001

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.

Adult↗

PubMed2001

An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a novel genetic risk factor for acute coronary events.

OBJECTIVES: Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha2B-adrenoceptor gene is associated with the risk for cardiovascular diseases. BACKGROUND: alpha2-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The alpha2-adrenoceptor subtype B mediates vasoconstriction in mice. A variant of the human alpha2B-adrenoceptor gene that encodes a D of three residues in an intracellular acidic motif has been shown to confer decreased receptor desensitization. This receptor variant could, therefore, be involved in diseases associated with enhanced vasoconstriction. METHODS: This study was part of a prospective population-based study investigating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. Nine hundred twelve men aged 46 to 64 years were followed for an average time of 4.5 years. RESULTS: In this study population, 192 men (21%) had the D/D genotype; 256 (28%) had the I/I genotype, and 464 (51%) had a heterozygous genotype. In a Cox model adjusting for other coronary risk factors, men with the D/D genotype had 2.2 times (95% confidence interval: 1.1 to 4.4, p = 0.02) the risk to experience an acute coronary event (n = 15 for D/D, 10 for I/I and 12 for I/D) compared with men carrying either of the other two genotypes. The alpha2B-adrenoceptor genotype was not associated with hypertension in this study population. CONCLUSIONS: The D/D genotype of the alpha2B-adrenoceptor is a novel genetic risk factor for acute coronary events, but not for hypertension.

Analysis of Variance↗

PubMed2001

Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in middle-aged men.

OBJECTIVES: We investigated the prognostic significance of exercise-induced silent myocardial ischemia in both high and low risk men with no prior coronary heart disease (CHD). BACKGROUND: Silent ischemia predicts future coronary events in patients with CHD, but there is little evidence of its prognostic significance in subjects free of CHD. METHODS: We investigated the association of silent ischemia, as defined by ST depression during and after maximal symptom-limited exercise test, with coronary risk in a population-based sample of men with no prior CHD followed for 10 years on average. RESULTS: Silent ischemia during exercise was associated with a 5.9-fold (95% CI 2.3 to 11.8) CHD mortality in smokers, 3.8-fold (95% CI 1.9 to 7.9) in hypercholesterolemic men and 4.7-fold (95% CI 2.4 to 9.1) in hypertensive men adjusting for other risk factors. The respective relative risks (RRs) of any acute coronary event were 3.0 (95% CI 1.7 to 5.1), 1.9 (95% CI 1.2 to 3.1) and 2.2 (95% CI 1.4 to 3.5). These associations were weaker in men without these risk factors. Furthermore, silent ischemia after exercise was a stronger predictor for the risk of acute coronary events and CHD death in smokers and in hypercholesterolemic and hypertensive men than in men without risk factors. CONCLUSIONS: Exercise-induced silent myocardial ischemia was a strong predictor of CHD in men with any conventional risk factor, emphasizing the importance of exercise testing to identify asymptomatic high risk men who could benefit from risk reduction and preventive measures.

Coronary Disease↗

PubMed2001

Associations between apolipoprotein E phenotype, glucose metabolism and cognitive function in men. An explorative study in a population sample.

AIMS: To investigate the associations of the apolipoprotein E phenotype (apoE) and disturbed glucose metabolism with cognitive function in a random population sample. METHODS: A cross-sectional study was conducted, in which 528 men aged 54 or 60 years were recruited randomly from a larger population-based sample of 1516 men. A subject was defined as having abnormal glucose tolerance (AGT), if he had a clinical diagnosis of diabetes, with either dietary or oral antidiabetic treatment or showed impaired glucose tolerance in an oral glucose tolerance test. The subjects were divided into three groups according to apolipoprotein E phenotypes: (a) E2/4, E3/4 or E4/4 (apoE E4); (b) E 3/3 (apoE E3); and (c) E2/2 or E2/3 (apoE E2). Memory function was examined using a word-list learning with Buschke's selective reminding method and test. Executive functions were assessed with the Trail Making Test A and B. RESULTS: Those subjects with apoE E2 and abnormal glucose metabolism demonstrated the worst cognitive executive control compared to other groups. Simple cognitive speed did not differ between the groups. CONCLUSIONS: The exploratory analyses revealed that subjects with apoE E2 allele and AGT had worse glycaemic control and cognitive executive control compared to other groups. Different apolipoprotein phenotypes together with impaired glucose tolerance may have different cumulative adverse effects on age-related cognitive performance. Some subgroups of subjects may be especially vulnerable to cognitive impairment.

Apolipoprotein E3↗