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Biomedical subjects

Veikko Salomaa

Publications and source records attributed to Veikko Salomaa.

At least 19 recordsLinked to original sources
PubMed2007

Trends in lifestyle factors affecting blood pressure in hypertensive and normotensive Finns during 1982-2002.

OBJECTIVE: To assess the trends in blood pressure (BP) affecting lifestyle factors in hypertensive and normotensive Finns from 1982 to 2002. DESIGN AND SETTING: Five independent cross-sectional population surveys conducted in 1982, 1987, 1992, 1997 and 2002 in the provinces of North Karelia and Kuopio in eastern Finland and the region of Turku-Loimaa in southwestern Finland. PARTICIPANTS: Stratified random samples of men and women aged 25-64 years were drawn from the national population register. The participants (n = 28 235) were classified into four groups according to their BP level and treatment status: normotensive, unaware hypertensive, aware but untreated hypertensive, and treated hypertensive subjects. MAIN OUTCOME MEASURES: Alcohol intake, body mass index (BMI), 24-h urinary sodium and potassium excretion (a subsample of 5849 subjects) and the proportion of subjects with leisure-time physical activity (LTPA) at least three times a week. RESULTS: Mean BMI increased significantly in all groups except in untreated hypertensive women. Alcohol intake increased in all men but especially in hypertensive women (P < 0.001). The 24-h urinary sodium excretion decreased significantly in all BP groups. The proportion of subjects with a recommended level of LTPA increased significantly and similarly in all BP groups (P < 0.001). CONCLUSIONS: The unfavourable trends observed in mean BMI and alcohol intake in the entire population should be reversed in order to decrease the frequency of hypertension in Finland. The health behaviours of hypertensive subjects should be carefully monitored and modified in a more systematic and efficient way than at present.

Adult↗
PubMed2006

The effect of correcting for troponins on trends in coronary heart disease events in Finland during 1993-2002: the FINAMI study.

AIMS: The object of this study is to analyse the trends in coronary events in Finland during 1993-2002, correcting for the effect of troponins. METHODS AND RESULTS: A population-based myocardial infarction register recorded all coronary events (n=14 782) in four geographical areas of Finland during 1993-2002. Correction coefficients for the effect of troponins were calculated on the basis of 4359 coronary events, with simultaneous determination of troponins and the 'old' enzymatic markers of myocardial injury. Coronary mortality declined steeply, except in women aged > or = 75 years. The incidence of first coronary events declined 2.0% (95% confidence interval -3.0, -0.9%) per year among men and 1.0% (-2.7, 0.6%) per year among women aged 35-74 years. After correcting for the effect of troponins, also the decline among women became statistically significant: 2.7% (-4.5, -0.8%) per year. The effect of troponins tended to be stronger in women and older individuals than in men and younger individuals. The 28-day case fatality declined among men, but not among women. The effect of troponins on case fatality trends was weak. CONCLUSION: Declining trends in the incidence of coronary events in Finland during 1993-2002 were partly hidden by the effect of troponins. Both incidence and case fatality declines have contributed to the decline in mortality.

Adult↗
PubMed2006

A two-base deletion -439delGC in the melanocortin-4 receptor promoter associated with early-onset obesity.

BACKGROUND/AIMS: Mutations in melanocortin-4 receptor (MC4R) are the most common genetic cause of human obesity. Mutations in MC4R promoter could also underlie obesity, but have so far not been reported. Transcription factor nescient helix-loop-helix 2 (Nhlh2) is a novel obesity candidate gene. We searched for mutations in MC4R promoter and Nhlh2 gene in 152 children with severe early-onset obesity. Lean subjects (n = 447) served as controls. METHODS: MC4R promoter and Nhlh2 gene were investigated by sequencing. Gel shifts and reporter gene assays were used to investigate a deletion in MC4R promoter. Mutation carriers were carefully characterised. Weight charts from index patients and relatives were analysed. RESULTS: We identified a deletion, -439delGC, in MC4R promoter in 2 severely obese, unrelated children and their family members, but not in controls. Index patients and mutation-carrying relatives were affected by early-onset obesity, while non-carriers had normal childhood weight development. The deletion is located at a potential Nhlh2-binding site and gel shift assays showed that Nhlh2 binds to this site. No significant differences in mutant compared to wild-type MC4R promoter activities were detected. No mutations were identified in Nhlh2 gene. CONCLUSION: We report an MC4R promoter mutation, -439delGC, associated with early-onset obesity and show that transcription factor Nhlh2 recognises this site in vitro. Nhlh2 mutations unlikely underlie severe human obesity.

Adolescent↗
PubMed2006

Risk alleles of USF1 gene predict cardiovascular disease of women in two prospective studies.

Upstream transcription factor 1 (USF1) is a ubiquitously expressed transcription factor controlling several critical genes in lipid and glucose metabolism. Of some 40 genes regulated by USF1, several are involved in the molecular pathogenesis of cardiovascular disease (CVD). Although the USF1 gene has been shown to have a critical role in the etiology of familial combined hyperlipidemia, which predisposes to early CVD, the gene's potential role as a risk factor for CVD events at the population level has not been established. Here we report the results from a prospective genetic-epidemiological study of the association between the USF1 variants, CVD, and mortality in two large Finnish cohorts. Haplotype-tagging single nucleotide polymorphisms exposing all common allelic variants of USF1 were genotyped in a prospective case-cohort design with two distinct cohorts followed up during 1992-2001 and 1997-2003. The total number of follow-up years was 112,435 in 14,140 individuals, of which 2,225 were selected for genotyping based on the case-cohort study strategy. After adjustment for conventional risk factors, we observed an association of USF1 with CVD and mortality among females. In combined analysis of the two cohorts, female carriers of a USF1 risk haplotype had a 2-fold risk of a CVD event (hazard ratio [HR] 2.02; 95% confidence interval [CI] 1.16-3.53; p = 0.01) and an increased risk of all-cause mortality (HR 2.52; 95% CI 1.46-4.35; p = 0.0009). A putative protective haplotype of USF1 was also identified. Our study shows how a gene identified in exceptional families proves to be important also at the population level, implying that allelic variants of USF1 significantly influence the prospective risk of CVD and even all-cause mortality in females.

Adult↗
PubMed2006

Modifiable risk factors have an impact on socio-economic differences in coronary heart disease events.

OBJECTIVES: To investigate the association of socio-economic status, defined by occupational class, income and education, with coronary heart disease (CHD) morbidity and mortality, and further to analyse to which extent modifiable risk factors may explain socio-economic differences in CHD risk. DESIGN: A population-based prospective cohort study including 9,061 men and 10,211 women aged 35-64 at baseline who participated in a cardiovascular risk factor survey in 1982, 1987, 1992 or 1997 in Finland. The subjects were followed for CHD events up till the end of 2001. Cox's proportional hazards model was used in the analysis. RESULTS: Male manual workers had a double risk of CHD death compared with upper-level employees (HR=2.00, 95% CI 1.35-2.97). This excess risk was reduced by 31% when adjusted for traditional cardiovascular risk factors and most of this reduction was due to smoking. CONCLUSIONS: Modifiable risk factors explained about a third of the excess CHD mortality between manual workers and upper-level employees in men. Among women the differences between socio-economic groups were not statistically significant.

Adult↗
PubMed2006

C-reactive protein, interleukin-6 and tumor necrosis factor alpha as predictors of incident coronary and cardiovascular events and total mortality. A population-based, prospective study.

Previous studies have shown an association between serum C-reactive protein (CRP) and cardiovascular disease (CVD) risk. The roles of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) are less well established. The aim of the present study was to analyze the associations of CRP, IL-6 and TNFalpha with incident coronary heart disease (CHD) events, CVD events, and total mortality. A random population sample, including men and women aged 25-64 years was examined in Finland in 1992. The sample size was 7,927 and 6,051 (76%) participated. The cohort was followed up until the end of 2001. During the follow-up, 151 incident CHD events, 205 CVD events and 183 deaths from any cause were observed. A stratified random subsample (n=313) was used as the comparison group. After adjustment for conventional CVD risk factors, CRP showed a significant association with CHD risk in men (HR=2.39, 1.08-5.28, comparing fourth quartile to the first quartile). This association remained significant after further adjustment for TNFalpha. TNFalpha also was a significant predictor of CHD among men, but the association was nonlinear (HR=2.21, 1.18-4.14 comparing the three upper quartiles to the first quartile). Further adjustment for CRP did not change this association substantially. Both CRP and TNFalpha predicted also all CVD events and total mortality among men. Among women the findings were nonsignificant. In conclusion, CRP and TNFalpha were significant, independent predictors of CHD and CVD events and total mortality among men. These findings provide further support to the important role of inflammation in the pathogenesis of CVD.

Adult↗
PubMed2006

Evaluation of lipid-lowering therapy and cholesterol goal attainment in Finland: the National FINRISK Study.

BACKGROUND: European and US study findings show that patients in primary care and specialty care are not adequately treated for cholesterol reduction. OBJECTIVE: To evaluate lipid-lowering treatment in Finland, estimate the proportions of subjects who are achieving cholesterol goals, and assess the influence of determinants on goal attainment. METHODS: Subgroup analysis of the FINRISK study, a national study of cardiovascular disease risk factors in Finland. Study participants, the subgroup of patients on lipid-lowering therapy from FINRISK, completed a postal self-administered questionnaire on health/health behavioral factors. Serum total cholesterol (TC) and other clinical variables were measured using a standardized protocol. Ten-year coronary risk was computed using Framingham risk equations. The influence of certain factors on goal attainment was determined by logistic regression analysis. The main outcome measure was the proportion of subjects who were receiving lipid-lowering therapy and achieved a TC goal of <5 mmol/L (<194 mg/dL). RESULTS: Among 9581 respondents, 622 subjects were on lipid-lowering therapy. Of these, 68 subjects were excluded because of missing data on TC and/or the type/dose of therapy. Among the 554 subjects included, 210 (38%) were secondary-prevention patients and 51% had 10-year coronary risk >/=20%. Approximately two-thirds of subjects were prescribed simvastatin (42%) or atorvastatin (26%), and about half (51%) were prescribed low-equipotency HMG-CoA reductase inhibitors (statins). There was no difference in equipotent doses of statins prescribed for primary and secondary prevention. About half (54%) of subjects did not attain their cholesterol goal (TC <5.0 mmol/L [194 mg/dL]). Subjects with coronary heart disease (odds ratio [OR] 3.00; 95% CI 2.07, 4.35) and patients prescribed medium-to-high equipotent statins (OR 1.93; 95% CI 1.35, 2.76) were more likely to achieve cholesterol goals, whereas postmenopausal women (OR 0.61; 95% CI 0.42, 0.88) were less likely than men to achieve cholesterol goals. CONCLUSION: Most (92%) patients receiving lipid-lowering therapy in a Finnish population were managed on statin monotherapy and approximately half of the patients did not achieve their recommended cholesterol goals. More effective and safe therapies are needed to enhance cholesterol goal attainment. These treatments might include regimens that act on two or more pharmacologic pathways.

Aged↗
PubMed2005

Cross-species analyses implicate Lipin 1 involvement in human glucose metabolism.

Recent studies in the mouse have demonstrated that variations in lipin expression levels in adipose tissue have marked effects on adipose tissue mass and insulin sensitivity. In the mouse, lipin deficiency prevents normal adipose tissue development, resulting in lipodystrophy and insulin resistance, whereas excess lipin levels promote fat accumulation and insulin sensitivity. Here, we investigated the effects of genetic variation in lipin levels on glucose homeostasis across species by analyzing lipin transcript levels in human and mouse adipose tissues. A strong negative correlation was observed between lipin mRNA levels and fasting glucose and insulin levels, as well as an indicator of insulin resistance (HOMA-IR), in both mice and humans. We subsequently analyzed the allelic diversity of the LPIN1 gene in dyslipidemic Finnish families, as well as in a case-control sample of obese (n = 477) and lean (n = 821) individuals. Alleles were defined by genotyping seven single nucleotide polymorphisms (SNPs) of the critical DNA region over the LPIN1 gene. Intragenic SNPs and corresponding allelic haplotypes exhibited associations with serum insulin levels and body mass index (P = 0.002-0.04). Both the expression levels in adipose tissue across species and genetic data in human study samples highlight the importance of lipin in glucose homeostasis and imply that allelic variants of this gene have significance in human metabolic traits.

Adipose Tissue↗
PubMed2005

Contribution of regulatory and structural variations in APOE to predicting dyslipidemia.

The objective of this study was to evaluate 1) whether non single nucleotide polymorphisms-coding (non-cSNP) in the apolipoprotein E gene (APOE) identified by resequencing studies contribute to statistically explaining dyslipidemia if variations in the two cSNPs in exon 4 that define the 2, 3, and 4 alleles are ignored, and 2) whether the contribution of these additional SNPs persists when variations in the cSNPs are considered. We used an ecological, multiple-population, data-mining strategy to identify single-SNP and two-SNP genotypes that distinguish between high and low levels of plasma lipids in three training samples, European-Americans from Rochester, MN, African-Americans from Jackson, MS, and Europeans from North Karelia, Finland. We found that a pair of SNPs located in the 5' region define genotypes A560T832/A560T832, A560T832/A560G832, and A560T832/T560T832, which distinguish between high and low levels of HDL-cholesterol (HDL-C), triglycerides (TG), and/or total cholesterol (T-C). The A560T832/- genotypes predicted high TG and high T-C in both genders in a large independent test sample from Copenhagen, Denmark. Prediction of high T-C in the Danish females was dependent on genotypes defined by the cSNPs. Our study suggests that both regulatory and structural variations should be considered when evaluating the utility of APOE for predicting dyslipidemia in the population at large.

Black or African American↗
PubMed2005

Coronary heart disease: from a disease of middle-aged men in the late 1970s to a disease of elderly women in the 2000s.

AIMS: To analyse secular changes in the prevalence of coronary heart disease (CHD) and to assess changes in the burden of CHD at population level. METHODS AND RESULTS: Data were used from two large cross-sectional health examination surveys representing the entire Finnish adult population in 1980 and 2000. In the 1978-80 survey, the sample covered 5101 individuals aged > or =45, of whom 88% participated. The 2000-2001 survey comprised 5310 individuals in the same age range. Participation rate in the health examination was 87%. Prevalence of CHD decreased in men and women under the age of 65 and increased among those aged > or =75. Prevalence of large Q-waves indicating previous myocardial infarction decreased in all male age groups and in women aged 65-74. The total estimated number of persons with CHD increased by 18% (95% CI=6-30) during the past 20 years in Finland. In 1980, the most dominant CHD group was men aged 45-64, whereas in 2000, women aged > or =75 comprised the largest CHD group. CONCLUSION: Although the prevalence of CHD has decreased among middle-aged persons, the number of CHD cases has increased during the past 20 years in Finland.

Age Distribution↗
PubMed2005

Explaining the decline in coronary heart disease mortality in Finland between 1982 and 1997.

In Finland since the 1980s, coronary heart disease mortality has declined more than might be predicted by risk factor reductions alone. The aim of this study was to assess how much of the decline could be attributed to improved treatments and risk factor reductions. The authors used the cell-based IMPACT mortality model to synthesize effectiveness of treatments and risk factor reductions with data on treatments administered to patients and trends in cardiovascular risk factors in the population. Cardiovascular risk factors were measured in random samples of patients in 1982 (n=8,501) and 1997 (n=4,500). Mortality and treatment data were obtained from the National Causes of Death Register, Hospital Discharge Register, social insurance data, and medical records. Estimated and observed changes in coronary heart disease mortality were used as main outcome measures. Between 1982 and 1997, coronary heart disease mortality rates declined by 63%, with 373 fewer deaths in 1997 than expected from baseline mortality rates in 1982. Improved treatments explained approximately 23% of the mortality reduction, and risk factors explained some 53-72% of the reduction. These findings highlight the value of a comprehensive strategy that promotes primary prevention programs and actively supports secondary prevention. It also emphasizes the importance of maximizing population coverage of effective treatments.

Adult↗
PubMed2005

Associations of leisure time physical activity, self-rated physical fitness, and estimated aerobic fitness with serum C-reactive protein among 3,803 adults.

OBJECTIVE: Serum C-reactive protein (CRP), a marker of systemic inflammation, is a risk factor for cardiovascular disease. Obesity and physical activity are associated with CRP, though population studies are sparse. METHODS AND RESULTS: We assessed the cross-sectional relationship of physical activity, self-rated fitness and estimated aerobic fitness with serum CRP among a population-based random sample of 3,803 Finnish adults aged 25-74 years. Conditioning, commuting and non-conditioning physical activity was measured by a recall and self-rated physical fitness by a questionnaire. A non-exercise test was used to estimate aerobic fitness. The combined association of aerobic fitness and waist-to-hip ratio (WHR) on CRP was also assessed. Self-rated fitness and aerobic fitness had inverse associations with CRP (adjusted for age, WHR, smoking, anti-hypertensive drugs, aspirin, diabetes, hypercholesterolemia, hormone replacement therapy and menopausal status) in both sexes (p < 0.001). An inverse age-adjusted association of conditioning and non-conditioning physical activity with CRP was found in both sexes. After further adjustments, associations remained significant in women for conditioning and non-conditioning activity (p < 0.001 and p = 0.010, respectively) and borderline significant in men (p = 0.074 and p = 0.070, respectively). Commuting physical activity was inversely associated with CRP among women only (p = 0.012). CONCLUSIONS: Physical activity and fitness may have an anti-inflammatory effect, which is independent of obesity.

Adult↗
PubMed2005

A new definition for myocardial infarction: what difference does it make?

AIMS: As a response to changing diagnostic tools of myocardial infarction (MI), new case definitions for acute coronary events were published in 2003 as the American Heart Association Scientific Statement. We assessed the new definition in hospitalized patients in a large population-based MI register study. METHODS AND RESULTS: We identified all suspected acute coronary syndromes with data either on troponin T or on troponin I and at least one of the enzymatic markers of myocardial injury (n=6104). The 2003 definition with the use of troponins identified 83% more definite MIs than the WHO MONICA definition using cardiac enzymes. The additional patients were older, had more often diabetes, and received less often thrombolysis and revascularization than those having MI by both definitions. Adjusting for age, sex, study area, and study year, the additional patients with their first MI aged 25-74 had a higher risk of cardiovascular death within 1 year than patients having definite MI by both definitions (hazard ratio 1.6, 95% CI 1.1-2.2). CONCLUSION: The changing diagnostic criteria present a considerable challenge for the assessment of long-term trends in MI events in the community as well as for longitudinal studies of the natural history of MI. The 2003 definition, when applied using troponins, identified a sizable new group of MI patients, among persons with suspected acute coronary syndrome, at high risk of a recurrent event.

Adult↗
PubMed2005

Diabetes worsens the outcome of acute ischemic stroke.

OBJECTIVE: To characterize acute stroke events in diabetic patients in a population-based stroke register and to determine the influence of diabetes on the outcome of acute stroke. METHODS: Four thousand three hundred and ninety patients were recorded in the FINMONICA and FINSTROKE registers after their first ischemic stroke from 1990 to 1998. We followed mortality and stroke outcome for up to 4 weeks after the onset of acute stroke. RESULTS: Of the 4390 patients who had had an ischemic stroke, 43.6% were male and 25.1% (1103) had diabetes. Their mean age was 72.4 (S.D. 12.0) years and this was similar in patients with and without diabetes (72.9 years versus 72.3 years, p=0.18). Subjects with diabetes were more likely to be hypertensive (55% versus 38%, p<0.001) and have a history of myocardial infarction (20% versus 16%, p<0.001) than the non-diabetic stroke patients. Mortality at 4 weeks from the onset was higher in diabetic than in non-diabetic patients (20.0% versus 16.9% p=0.020). At day 28 after the stroke attack, diabetic patients were more likely to be disabled when compared with non-diabetic subjects (43.3% versus 33.5%, p<0.001). Using logistic regression analysis, adjusted for age-group, sex, previous medical history (MI, AF or TIA), diabetes was found to be a significant predictor of disability after stroke (OR=1.51, 95% CI 1.27-1.81). CONCLUSIONS: Diabetes, which affected one-fourth of the ischemic stroke patients on our register, was associated with a higher risk of death and disability after the onset of stroke. Preventing diabetes in the elderly population improves the short-term prognosis of acute ischemic stroke.

Acute Disease↗
PubMed2005

Trends in fatal and nonfatal strokes among persons aged 35 to > or =85 years during 1991-2002 in Finland.

BACKGROUND AND PURPOSE: Declining trends in the incidence and mortality of stroke have been observed in Finland since the beginning of the 1980s until 1997. In this study we analyzed the trends in fatal and nonfatal strokes in Finland during 1991-2002. METHODS: The Finnish Hospital Discharge Register was linked to the National Causes of Death Register to produce a Cardiovascular Disease Register, which includes data on 410 760 cerebrovascular events (International Statistical Classification of Diseases, 10th Revision [ICD-10] codes I60-I69) in patients aged > or =35 years in 1991-2002. RESULTS: Age-standardized incidence of first-ever stroke (ICD-10 codes I60-I64, excluding I63.6) per 100 000 persons declined during 1991-2002 annually by 2.2% (95% CI, -2.4% to -1.9%) among men and 2.5% (-2.8% to -2.2%) among women aged 35 to 74 years. In patients aged 75 to 84 years, the change in the incidence of first-ever stroke was -2.6% per year (-3.0% to -2.2%) among men and -3.2% per year (-3.5% to -2.9%) among women. A similar trend was observed also in the oldest age group, in patients aged > or =85 years. Among patients aged 35 to 74 years, the 28-day case fatality of first-ever stroke declined annually by 3.2% (-3.9% to -2.5%) among men and by 3.0% (-3.8% to -2.2%) among women. A significant decrease was found in the 28-day case fatalities of all subtypes of stroke in this age group. CONCLUSIONS: The favorable development in stroke incidence, mortality, and case-fatality has continued in Finland during 1991-2002.

Adult↗
PubMed2005

Association of criteria pollutants with plasma hemostatic/inflammatory markers: a population-based study.

To elucidate the health effects of air pollution, the short-term association of criteria pollutants (particles <10 microm in diameter [PM(10)], O(3), CO, NO(2), and SO(2)) with hemostatic and inflammatory markers were examined using a population-based sample of 10,208 middle-age males and females of the biracial cohort of Atherosclerosis Risk in Communities (ARIC) study. For each participant, we calculated the following pollutant exposures 1-3 days prior to the randomly allocated cohort examination date: PM(10), CO, NO(2), and SO(2) as 24-h averages, and O(3) as an 8-h average of the hourly measures. The hemostatic/inflammatory factors included fibrinogen, factor VIII-C, von Willebrand factor (vWF), albumin, and white blood cell count (WBC). Linear regression models were used to adjust for cardiovascular disease (CVD) risk factors, demographic and socioeconomic variables, and relevant meteorological variables. One standard deviation (SD) increment of PM(10) (12.8 microg/m(3)) was significantly (P < 0.05) associated with 3.93% higher of vWF among diabetics and 0.006 g/dl lower of serum albumin among persons with a history of CVD. One SD increment of CO (0.60 p.p.m.) was significantly (P < 0.01) associated with 0.018 g/dl lower of serum albumin. Significant curvilinear associations, indicative of threshold effects, for PM(10) with factor VIII-C, O(3) with fibrinogen and vWF, and SO(2) with factor VIII-C, WBC, and serum albumin were found. This population-based study suggest that the hemostasis/inmflammation markers analyzed, which are linked to higher risk of CHD, are associated adversely with environmentally relevant ambient pollutants, with the strongest associations in the upper range of the pollutant distributions, and in persons with a positive history of diabetes and CHD.

Air Pollutants↗
PubMed2005

Gender differences in the treatment and secondary prevention of CHD at population level.

OBJECTIVES: Treatment and secondary prevention measures, received by persons with coronary heart disease (CHD), are insufficiently known at the moment. The aim of this study was to investigate the state of treatment and secondary prevention of CHD in a population-based sample and to analyze possible gender differences in different age groups. DESIGN: 300 men and 300 women with CHD were identified from a nationally representative health examination survey with 88% participation rate, carried out in Finland in 2000-2001. RESULTS: Revascularization had been performed on 34% (95% confidence interval 29, 40%) of men and 13% (8, 18%) of women. Moreover, 76% (71, 81%) of the men and 63% (57, 69%) of the women used antithrombotic medications. Two thirds of both men and women used beta-blockers and one third lipid-lowering medication. Smoking was more common among men, whereas obesity and high total cholesterol concentration were more common among women. CONCLUSIONS: Secondary prevention of CHD is far from optimal and there are gender differences in the care of CHD.

Adrenergic beta-Antagonists↗