Education as a moderator of genetic risk for higher body mass index: prospective cohort study from childhood to adulthood.

OBJECTIVES: The life-course development of body mass index (BMI) may be driven by interactions between genes and obesity-inducing social environments. We examined whether lower parental or own education accentuates the genetic risk for higher BMI over the life course, and whether diet and physical activity account for the educational differences in genetic associations with BMI. SUBJECTS/METHODS: The study comprised 2441 participants (1319 women, 3-18 years at baseline) from the prospective, population-based Cardiovascular Risk in Young Finns Study. BMI (kg/m2) trajectories were calculated from 18 to 49 years, using data from six time points spanning 31 years. A polygenic risk score for BMI was calculated as a weighted sum of risk alleles in 97 single-nucleotide polymorphisms. Education was assessed via self-reports, measured prospectively from participants in adulthood and from parents when participants were children. Diet and physical activity were self-reported in adulthood. RESULTS: Mean BMI increased from 22.6 to 26.6 kg/m2 during the follow-up. In growth curve analyses, the genetic risk score was associated with faster BMI increase over time (b=0.02, (95% CI, 0.01-0.02, P<0.001)). The association between the genetic risk score and BMI was more pronounced among those with lower educational level in adulthood (b=-0.12 (95% CI, -0.23-0.01); P=0.036)). No interaction effect was observed between the genetic risk score and parental education (b=0.05 (95% CI, -0.09-0.18; P=0.51)). Diet and physical activity explained little of the interaction effect between the genetic risk score and adulthood education. CONCLUSIONS: In this prospective study, the association of a risk score of 97 genetic variants with BMI was stronger among those with low compared with high education. This suggests lower education in adulthood accentuates the risk of higher BMI in people at genetic risk.

Mobility and muscle strength in male former elite endurance and power athletes aged 66-91 years.

The aim of this cross-sectional study was to compare mobility and muscle strength in male former elite endurance and power athletes aged 66-91 years (n = 150; 50 men in both former elite athlete groups and in their control group). Agility, dynamic balance, walking speed, chair stand, self-rated balance confidence (ABC-scale), jumping height, and handgrip strength were assessed. Former elite power athletes had better agility performance time than the controls (age- and body mass index, BMI-adjusted mean difference -3.6 s; 95% CI -6.3, -0.8). Adjustment for current leisure time physical activity (LTPA) and prevalence of diseases made this difference non-significant (P = 0.214). The subjects in the power sports group jumped higher than the men in the control group (age- and BMI-adjusted mean differences for vertical squat jump, VSJ 4.4 cm; 95% CI 2.0, 6.8; for countermovement jump, CMJ 4.0 cm; 95% CI 1.7, 6.4). Taking current LTPA and chronic diseases for adjusting process did not improve explorative power of the model. No significant differences between the groups were found in the performances evaluating dynamic balance, walking speed, chair stand, ABC-scale, or handgrip strength. In conclusion, power athletes among the aged former elite sportsmen had greater explosive force production in their lower extremities than the men in the control group.

Cardiovascular health in former elite male athletes.

To increase our knowledge on the effects of previous and current physical activity on cardiovascular health, we studied a group of Finnish male former elite athletes (endurance, n = 49; power, n = 50) and their 49 age and area-matched controls, aged 64-89 years. Body mass index (BMI), fasting serum glucose, lipids, blood pressure, and ultrasonography of cardiac and carotid artery structure and function were measured. Former endurance athletes smoked less, had lower prevalence of hypertension, and had higher intensity and volume of leisure time physical activity (LTPA) than the controls. No difference was detected in cardiac or carotid artery structure and function between these groups. Former athletes performing high-intensity LTPA were slightly younger (possible selection bias), had lower BMI and waist circumference, lower use of antihypertensives, lower prevalence of diabetes, lower pulse wave velocity, and higher carotid artery elasticity than former athletes not performing high-intensity LTPA. In conclusion, former athletes had a higher intensity and volume of LTPA than the controls. Athletes performing vigorous LTPA had more elastic arteries than athletes performing moderately or no LTPA. Vigorous LTPA through the whole lifetime associates with good cardiovascular health, although the previous medical history may play an important role.

Former male elite athletes have better metabolic health in late life than their controls.

Elite-class athletes have longer life expectancy and lower risk for chronic noncommunicable diseases possibly because of physically active and healthier lifestyle. In this study, we assessed former male Finnish elite-class athletes' (n = 392) and their matched controls' (n = 207) body composition, and risk for the metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD) in later life. Compared with the controls, the former athletes had lower body fat percentage (24.8% vs 26.0%, P = 0.021), lower risk for MS [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.40-0.81], and NAFLD (OR 0.61, 95% CI 0.42-0.88). High volume of current leisure-time physical activity (LTPA) was associated with lower body fat percentage (P for trend < 0.001). When current volume of LTPA increased 1 MET h/week, the risk of MS and NAFLD decreased (OR 0.99, 95% CI 0.98-0.99 and OR 0.97, 95% CI 0.96-0.98, respectively). Although a career as an elite-class athlete during young adulthood may help to protect from developing metabolic syndrome, present exercise levels and volume of LTPA seem equally important as well.

Fall-related risk factors and heel quantitative ultrasound in the assessment of hip fracture risk: a 10-year follow-up of a nationally representative adult population sample.

UNLABELLED: Maximal walking speed and quantitative ultrasound index (QUI) were significant and independent predictors of hip fracture among subjects aged ≥ 55 years. A model including readily available variables along with simple fall-related factors may be clinically useful in the assessment of hip fracture risk even without a QUI measurement. INTRODUCTION: This study assessed fall-related risk factors along with heel bone quantitative ultrasound (QUS) measurements for the prediction of hip fracture during a mean follow-up of 9.8 years in a nationally representative population sample. METHODS: The study population consisted of 2,300 subjects (1,331 women and 969 men) aged 55 years or over, who had participated in a comprehensive health survey in 2000-2001. Information on the subjects' health and fall-related risk factors was obtained with interviews, questionnaires and tests carried out by specially trained professionals. QUS measurements were made by means of the Hologic Sahara device. First emerging cases of hip fracture were identified from the National Hospital Discharge Register. RESULTS: During the follow-up, 96 subjects sustained a hip fracture. Slow maximal walking speed, low quantitative ultrasound index (QUI), high age, tallness, short waist circumference, Parkinson's disease and the number of central nervous system active medication were significant and independent predictors of hip fracture. The model including all of these risk factors explained 68 % of the variation in hip fracture risk. Excluding QUI from this model reduced the percentage to 66%. CONCLUSIONS: Maximal walking speed and QUI were significant and independent predictors of hip fracture. A model including readily available variables such as age, gender, height and waist circumference along with simple fall-related factors may be of clinical use in the assessment of hip fracture risk even without a QUS measurement.

Quantitative ultrasound measurements and vitamin D status in the assessment of hip fracture risk in a nationally representative population sample.

SUMMARY: Adjusted for age, gender, height and weight, calcaneal quantitative ultrasound (QUS) and serum 25-hydroxyvitamin D (S-25(OH)D) proved to be significant predictors of hip fracture among subjects aged ≥50 years. Even if their contribution to the predictive power was modest, they may be useful in the assessment of hip fracture risk in the elderly. INTRODUCTION: This study assessed calcaneal QUS measurements, S-25(OH)D and several other factors for the prediction of hip fracture risk in a nationally representative population sample. METHODS: The study population consisted of 3,305 subjects (1,872 women), aged 50 years or over, who had participated in a comprehensive health survey. QUS measurements were made by means of the Hologic Sahara device. S-25(OH)D was measured by radioimmunoassay. Emerging cases of hip fracture were identified from the National Hospital Discharge Register. RESULTS: During a mean follow-up of 8.4 years, 95 subjects sustained a hip fracture. After adjusting for age, gender, height, weight and each other, a 1 standard deviation increment in the quantitative ultrasound index (QUI) (21.7) and in S-25(OH)D (17.5 nmol/L) reduced the risk of hip fracture by 40 % (hazard ratio [HR] = 0.60, 95 % confidence interval [CI] = 0.42-0.86) and by 31 % (HR = 0.69, 95 % CI = 0.55-0.87), respectively. The predictive power of a model including age, gender, height and weight was improved by about 8 % after the addition of QUI and S-25(OH)D. Among subjects aged 75 years or over, the corresponding improvement was about 130 %. CONCLUSIONS: QUI and S-25(OH)D were significant and independent predictors of hip fracture. However, their ability to increase the predictive power of a statistical model including readily available simple variables such as age, gender, height and weight was rather modest. Still, our findings suggest that QUI and S-25(OH)D may be of clinical use in the assessment of hip fracture risk particularly in the elderly.

Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis.

BACKGROUND: Fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are shown to protect from cardiovascular diseases (CVD). However, most fish contain environmental contaminants such as dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and methylmercury (MeHg) that may have adverse effects on cardiovascular health. OBJECTIVE: Our aim was to elucidate the associations of fish consumption, omega-3 PUFAs, environmental contaminants with low-grade inflammation, early atherosclerosis, and traditional CVD risk factors. METHODS: The Health 2000 survey participants (n=1173) represented the general Finnish population and the Fishermen study participants (n=255) represented a population with high fish consumption and high exposure to environmental contaminants. Model-adjusted geometric means and tests for linear trend were calculated for CVD risk factors by tertiles of fish consumption and serum omega-3 PUFAs, and additionally in the Fishermen study only, by tertiles of serum PCDD/F+PCB, and blood MeHg. RESULTS: Serum triglyceride decreased across omega-3 PUFA tertiles in both sexes and studies. Insulin resistance, C-reactive protein, tumour necrosis factor α, and interleukin 6 decreased across omega-3 PUFA tertiles among the Health 2000 survey participants. Among the Fishermen study men, insulin resistance and arterial stiffness indicated by ß-stiffness index tended to increase and the RR estimate for carotid artery plaque tended to decrease across tertiles of PCDD/F+PCB and MeHg. CONCLUSION: Previously established hypotriglyceridemic and anti-inflammatory effects of omega-3 PUFAs were seen also in this study. The hypothesised favourable effect on insulin sensitivity and arterial elasticity was suggested to be counteracted by high exposure to environmental contaminants but the effect on plaque prevalence appeared not to be harmful.

Hyperfiltration in type 1 diabetes: does it exist and does it matter for nephropathy?

AIMS/HYPOTHESIS: Hyperfiltration is widely regarded as a contributing factor to the development of microalbuminuria and progressive nephropathy in type 1 diabetes. However, recent studies have questioned this conclusion. METHODS: To address this conflicting evidence, we examined the association between hyperfiltration and progression to microalbuminuria in 2,318 adults with type 1 diabetes. We also compared the estimated GFR in our diabetic patients with rates observed in 6,247 adults from the Finnish general population, using age- and sex-specific z scores. RESULTS: The distribution of estimated GFR in adults with type 1 diabetes and normoalbuminuria was not significantly different from that expected in the general population (p = 0.51, Mann-Whitney test). Type 1 diabetic patients with a higher estimated GFR were also no more likely to develop microalbuminuria over a median of 5.2 years of follow-up than those with normal estimated GFR. This was the case regardless of whether hyperfiltration was defined by an absolute threshold, deciles of estimated GFR or a z score, using creatinine- or cystatin-based clearance formulas in men or in women. CONCLUSIONS/INTERPRETATION: Together with other studies, these data suggest that creatinine- or cystatin-based estimates of GFR do not predict the development of microalbuminuria in patients with type 1 diabetes. Moreover, in the absence of incipient or overt nephropathy, conventionally determined renal function in patients with type 1 diabetes appears no different from that in the general population. This is hardly surprising, given that these individuals, by all definitions, do not have kidney disease.

Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes.

OBJECTIVES: To examine whether interleukin-1 receptor antagonist (IL-1Ra) is a predictor for clinically incident diabetes in subjects with metabolic syndrome (MetS) and whether its predictive power is independent of C-reactive protein (CRP), an established marker of inflammation. We further examined whether genetic variants at the interleukin-1 (IL-1) locus would predict clinically incident diabetes. DESIGN: Two observational prospective cohort studies. SETTING: Two separate cohorts, Health 2000 and FINRISK 1997, followed up for an average of 7.1 and 10.8 years, respectively. SUBJECTS: Random population samples consisting of 5511 subjects aged 30-74 years in Health 2000 and 7374 subjects aged 25-74 years in FINRISK 1997. RESULTS: During follow-up, 141 cases of clinically incident diabetes were observed amongst subjects with MetS at baseline in Health 2000 and 248 cases in FINRISK 97. After adjustment for multiple traditional risk factors of diabetes, including age and body mass index, IL-1Ra was a significant (P < 0.01) predictor of incident diabetes amongst men in both cohorts and amongst women in FINRISK 1997. Further adjustment for CRP reduced the hazard ratios only slightly. Genetic analyses produced nominally significant associations for three single-nucleotide polymorphisms: rs3213448 in IL-1 receptor antagonist (IL1RN), rs1143634 in IL-1 beta (IL1B) and rs1800587 in IL-1 alpha (IL1A). The two latter variants had an interaction with gender (P = 0.023 and 0.002, respectively) suggesting the presence of gender-specific associations with the risk of clinically incident diabetes. CONCLUSIONS: IL-1Ra predicted the progression of MetS to clinically incident diabetes independently of CRP and other risk factors. Genetic variation in the IL-1 locus may have gender-specific associations with the risk of type 2 diabetes.

Pentraxin 3 (PTX3) is associated with cardiovascular risk factors: the Health 2000 Survey.

Pentraxin 3 (PTX3) is a novel candidate immunoinflammatory marker that has been reported to be associated with cardiometabolic risk factors and to predict adverse outcomes in individuals with cardiovascular disease (CVD). Despite being a member of the same pentraxin protein family as C-reactive protein (CRP), PTX3 probably reflects different aspects of CVD pathogenesis. In this study, we assessed plasma PTX3 correlates and determinants in the Health 2000 Survey population, which comprised n = 403 insulin-resistant subjects, n = 845 hypercholesterolaemic subjects and n = 311 hypertensive subjects, all aged between 46 and 76 years. In insulin-resistant subjects the PTX3 concentration was found to correlate directly with age, pulse pressure and indoleamine 2,3-dioxygenase (IDO) enzyme activity and inversely with total and low-density lipoprotein (LDL) cholesterol. In hypercholesterolaemic subjects, the PTX3 concentration correlated directly with HDL cholesterol, systolic blood pressure and pulse pressure, whereas in hypertensive subjects, the PTX3 concentration correlated directly with systolic blood pressure, pulse pressure and IDO activity. No correlation was observed between the concentrations of PTX3 and CRP, adiposity indicators or indicators of subclinical atherosclerosis in any of the subject groups. PTX3 concentration variations were attributed to variations in LDL cholesterol and IDO activity in insulin-resistant subjects and to pulse pressure in hypercholesterolaemic and hypertensive subjects. These results indicate that, in individuals at high risk of CVD, the PTX3 concentration is associated with cardiovascular risk factors but not with subclinical atherosclerosis.

Parity and risk of hip fracture in postmenopausal women.

UNLABELLED: Hip fracture risk was assessed according to parity among postmenopausal women. Compared with nulliparous women, the fracture risk was lower in women with three or more births. INTRODUCTION: Parity was assessed for long-term prediction of hip fracture in postmenopausal women. METHODS: Postmenopausal women (n= 2,028) aged 45 or over with no history of hip fracture were studied. From 1978 to 1980, all of them had participated in a comprehensive health survey based on a nationally representative population sample. Emerging cases of hip fracture were identified from the National Hospital Discharge Register during a follow-up period extending up to 17 years. RESULTS: The risk of hip fracture was lower among parous women compared with nulliparous women. The model adjusted for age showed a significant inverse association between parity as a continuous variable and the risk of hip fracture [RR = 0.74; 95% confidence interval (CI), 0.61-0.90] per an increment of one standard deviation (2.4 births). Adjusted for age, menopausal age, level of education, body mass index, vitamin D status, alcohol consumption, smoking history, leisure time physical activity, and self-rated health, the relative risk was 0.50 (95% CI, 0.32-0.79) for women with three or more births and 0.85 (95% CI, 0.55-1.32) for women with one to two births as compared with nulliparous women. CONCLUSION: Parity, three or more births in particular, predicts a lowered risk of hip fracture in the long run.

Follow-ups of the Cardiovascular Risk in Young Finns Study in 2001 and 2007: levels and 6-year changes in risk factors.

OBJECTIVES: To examine cardiovascular risk factor levels in 2007 and their 6-year changes between 2001 and 2007 using the data collected in the follow-ups of the Cardiovascular Risk in Young Finns Study. DESIGN: Population-based follow-up study. SUBJECTS: A total of 2204 healthy Finnish adults aged 30-45 years (1210 women; 994 men). MAIN OUTCOME MEASURES: Levels in 2007 and changes between 2001 and 2007 of lipids, insulin, glucose, blood pressure, smoking, body mass index, alcohol consumption, waist and hip circumferences. RESULTS: The mean serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations in 30- to 45-year-old adults were 5.05, 3.09, 1.34 and 1.40 mmol L(-1), respectively. Significant changes (P < 0.05) between 2001 and 2007 in 30- to 39-year-old subjects included a decrease in total cholesterol (-6.6% in men, -5.8% in women), LDL-cholesterol (-10.2% and -11.6%) and an increase in diastolic blood pressure (3.5% and 3.9%). Waist circumference (1.8% and 5.5%) and systolic blood pressure increased in 36-39 year olds (2.3% and 2.3%). HDL-cholesterol increased in 30- to 33-year-old women (5.8%) Glucose levels increased in 30- to 39-year-old women (3.7%) and 36- to 39-year-old men (3.6%). Smoking prevalence decreased in 36- to 39-year-old men from 29.8% to 22.2%. CONCLUSIONS: The 6-year changes in total cholesterol, LDL-cholesterol and HDL-cholesterol in young Finns were favourable between 2001 and 2007. However, waist circumference, glucose and blood pressure levels increased. Therefore, continuous efforts are still needed in fighting against cardiovascular risk factors.

Serum amyloid A is independently associated with metabolic risk factors but not with early atherosclerosis: the Cardiovascular Risk in Young Finns Study.

BACKGROUND: Serum amyloid A (SAA) is a sensitive marker of inflammation and its elevation has been implicated in obesity and in cardiovascular disease, yet data on its regulation in young adults or on its role in early atherosclerosis is scarce. We investigated which factors explain the variation in SAA and analysed whether SAA could be associated with preclinical atherosclerosis. METHODS: Serum amyloid A levels were measured in participants of the Cardiovascular Risk in Young Finns Study (n = 2280, n = 1254 women, n = 1026 men). Correlates and determinants of SAA were analysed and the effect of SAA on subclinical atherosclerosis, measured as intima-media thickness (IMT) and carotid artery compliance, was evaluated with risk-factor adjusted models. RESULTS: Serum amyloid A correlated directly and independently of BMI with C-reactive protein (CRP), waist circumference and leptin in both sexes, with total cholesterol, LDL cholesterol and ApolipoproteinA1 (ApoA1) in women and with triglycerides, insulin levels and insulin resistance in men. Use of combined oral contraceptives and intrauterine device was also associated with SAA levels. Determinants for SAA included CRP, leptin and ApoA1 in women, and CRP, leptin and HDL cholesterol in men. SAA levels correlated with carotid compliance in both sexes and with IMT in men, yet SAA had no independent effect on IMT or carotid compliance in multivariable analysis. CONCLUSIONS: Serum amyloid A was associated with several metabolic risk factors but was not an independent predictor of IMT or carotid artery compliance. Further longitudinal studies will show whether SAA holds a prognostic value as a risk marker, analogously to CRP.

Common candidate gene variants are associated with QT interval duration in the general population.

OBJECTIVES: QT interval prolongation is associated with increased risk of sudden cardiac death at the population level. As 30-40% of the QT-interval variability is heritable, we tested the association of common LQTS and NOS1AP gene variants with QT interval in a Finnish population-based sample. METHODS: We genotyped 12 common LQTS and NOS1AP genetic variants in Health 2000, an epidemiological sample of 5043 Finnish individuals, using Sequenom MALDI-TOF mass spectrometry. ECG parameters were measured from digital 12-lead ECGs and QT intervals were adjusted for age, gender and heart rate with a nomogram (Nc) method derived from the present study population. RESULTS: The KCNE1 D85N minor allele (frequency 1.4%) was associated with a 10.5 ms (SE 1.6) or 0.57 SD prolongation of the adjusted QT(Nc) interval (P=3.6 x 10(-11)) in gender-pooled analysis. In agreement with previous studies, we replicated the association with QT(Nc) interval with minor alleles of KCNH2 intronic SNP rs3807375 [1.6 ms (SE 0.4) or 0.08 SD, P=4.7 x 10(-5)], KCNH2 K897T [-2.6 ms (SE 0.5) or -0.14 SD, P=2.1 x 10(-7)] and NOSA1P variants including rs2880058 [4.0 ms (SE 0.4) or 0.22 SD, P=3.2 x 10(-24)] under additive models. CONCLUSIONS: We demonstrate that each additional copy of the KCNE1 D85N minor allele is associated with a considerable 10.5 ms prolongation of the age-, gender- and heart rate-adjusted QT interval and could thus modulate repolarization-related arrhythmia susceptibility at the population level. In addition, we robustly confirm the previous findings that three independent KCNH2 and NOSA1P variants are associated with adjusted QT interval.

Obesity, adipokines and asthma.

BACKGROUND: The prevalence of asthma and obesity is increasing concomitantly, but many aspects of this link are unclear. Our objective was to examine whether obesity is associated with asthma in three time points of life, and whether immunomodulatory adipokines, leptin and adiponectin are linked to overweight-associated asthma. METHODS: We studied the association between obesity and asthma at ages 3-18 years [mean (SD), 10 years (5), n = 3582, year 1980], 9-24 years [16 years (5), n = 2764, 1986] and 24-39 years [32 years (5), n = 2620, 2001] in a prospective cohort study and further tested for associations with serum leptin and adiponectin concentrations. Data on allergy status, smoking and other laboratory values (serum insulin, plasma C-reactive protein and serum lipid values) were also analyzed. RESULTS: Allergy and parental asthma were significantly associated with asthma at all ages. At ages 24-39 years, but not earlier, body mass index (BMI) (odds ratio, OR 1.05; P = 0.019) and female gender (OR 1.56; P = 0.031) were independently associated with asthma. Increase in BMI was also associated with incident asthma during adulthood (OR 1.08; P = 0.030). Levels of leptin, adiponectin or any other obesity-related biomarker were not independently associated with asthma. CONCLUSIONS: Asthma is linked with obesity in adults, but our results do not support a significant role for leptin, adiponectin or any other obesity-related biomarker studied in this association. Other factors should be sought for better understanding the connection between obesity and asthma.

Metabolic syndrome and short-term heart rate variability in young adults. The cardiovascular risk in young Finns study.

AIMS: Heart rate variability (HRV) can be used to estimate autonomic nervous control of the cardiovascular system. In middle-aged subjects, the metabolic syndrome (MetS) is associated with lower HRV. We hypothesized that alterations in autonomic balance are already present in young adults with the MetS, and analysed the association of short-term HRV with the MetS (using the National Cholesterol Education Program definition), in 1889 subjects aged 24-39 years. METHODS: Short-term (3 min) HRV analysis included high-frequency (HF), low-frequency (LF) and total (TP) spectral components of HRV and LF/HF ratio. RESULTS: The presence of the MetS was associated with lower HF, LF and TP in men and women, and with higher LF/HF ratio in women. In men, waist circumference was the strongest individual MetS component that associated with HRV. After adjustments for age and heart rate, MetS was associated with lower HF and higher LF/HF ratio in women, but only with a lower TP in men (all P < 0.05). CONCLUSIONS: MetS is associated with lower HRV in young adults. The individual components of MetS are differentially associated with HRV in men and in women. Our results are consistent with lower vagal activity and a possible increase in sympathetic predominance in women with the MetS. This sex difference in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in women than in men.

Pre-eclampsia is a risk factor of carotid artery atherosclerosis.

BACKGROUND: A history of pre-eclampsia has been shown to be associated with an increased risk of subsequent coronary artery disease. The intima-media thickness of carotid arteries and the detection of plaques are useful measures as regards preclinical atherosclerosis. The aim of this study was to examine whether women with a history of pre-eclampsia more often show signs of atherosclerosis compared with 2 control groups. METHODS: We used data from a large Finnish cross-sectional health examination survey. We had women with previous pre-eclampsia (n = 35) or pregnancy-induced hypertension (n = 61) and 2 control groups. Laboratory tests and physical examination were performed. Information on reproductive and medical history was obtained at the home interview. Carotid atherosclerosis was assessed by ultrasonography. RESULTS: The women with previous pre-eclampsia had significantly (p = 0.008) more atherosclerotic plaques than the healthy parous controls. The intima-media thickness in the women with previous pre-eclampsia also tended to be higher than in the other groups, although the differences did not reach statistical significance. In logistic regression analysis, advanced age (OR: 1.08; 95% CI: 1.04-1.13; p < 0.001) and pre-eclampsia (OR: 3.63; 95% CI: 1.50-8.79; p = 0.004) were independent risk factors as regards plaque, and in linear regression analysis advanced age (estimate: 0.012; 95% CI: 0.010-0.014; p < 0.001), HDL cholesterol (estimate: -0.049; 95% CI: -0.088 to -0.010; p = 0.013), systolic blood pressure, BMI (estimate: 0.005; 95% CI: 0.000-0.009; p = 0.043) and high-sensitivity C-reactive protein (estimate: -0.003; 95% CI: -0.007 to -0.000; p = 0.048) were independent risk factors with respect to intima-media thickness. CONCLUSIONS: Our data suggest that pre-eclampsia is an independent risk factor as regards developing plaque later in life.

Indoleamine 2,3-dioxygenase activity associates with cardiovascular risk factors: the Health 2000 study.

Indoleamine 2,3-dioxygenase (IDO) is an important immunomodulator suppressing the activation of T lymphocytes, and its level in blood is increased in several autoimmune and inflammatory diseases. We have previously shown that this activity associates with several signs and risk factors of atherosclerosis in 24 to 39-year-old females. Now we repeat this analysis in an older population (n = 921, age range 46-76 years), i.e. in a population with more advanced atherosclerosis. IDO activity had a significant positive correlation in both sexes with carotid artery intima/media thickness (IMT), an early marker of atherosclerosis. In females, a significant negative correlation with HDL cholesterol and a positive correlation with triglycerides levels was observed. The association with IMT did not remain significant after adjustment with classical risk factors of atherosclerosis. It is thus concluded that IDO is a sensitive marker of atherosclerosis--or the inflammatory response associated with it--but does not have an independent role in the pathogenesis of this disease.

Insulin action on heart and skeletal muscle glucose uptake in essential hypertension.

Essential hypertension is characterized by skeletal muscle insulin resistance but it is unknown whether insulin resistance also affects heart glucose uptake. We quantitated whole body (euglycemic insulin clamp) and heart and skeletal muscle (positron emission tomography and 18F-fluoro-2-deoxy-D-glucose) glucose uptake rates in 10 mild essential hypertensive (age 33 +/- 1 yr, body mass index 23.7 +/- 0.8 kg/m2, blood pressure 146 +/- 3/97 +/- 3 mmHg, VO2max 37 +/- 3 ml/kg per min) and 14 normal subjects (29 +/- 2 yr, 22.5 +/- 0.5 kg/m2, 118 +/- 4/69 +/- 3 mmHg, 43 +/- 2 ml/kg per min). Left ventricular mass was similar in the hypertensive (155 +/- 15 g) and the normotensive (164 +/- 13 g) subjects. In the hypertensives, both whole body (28 +/- 3 vs 44 +/- 3 mumol/kg per min, P < 0.01) and femoral (64 +/- 11 vs 94 +/- 8 mumol/kg muscle per min, P < 0.05) glucose uptake rates were decreased compared to the controls. In contrast, heart glucose uptake was 33% increased in the hypertensives (939 +/- 51 vs 707 +/- 46 mumol/kg muscle per min, P < 0.005), and correlated with systolic blood pressure (r = 0.66, P < 0.001) and the minute work index (r = 0.48, P < 0.05). We conclude that insulin-stimulated glucose uptake is decreased in skeletal muscle but increased in proportion to cardiac work in essential hypertension. The increase in heart glucose uptake in mild essential hypertensives with a normal left ventricular mass may reflect increased oxygen consumption and represent an early signal which precedes the development of left ventricular hypertrophy.

Home-measured blood pressure is more strongly associated with electrocardiographic left ventricular hypertrophy than is clinic blood pressure: the Finn-HOME study.

Electrocardiographic evidence of left ventricular hypertrophy (ECG-LVH) has a grave prognostic significance in hypertensive patients. The purpose of our study was to assess whether ECG-LVH is more strongly associated with home-measured blood pressure (BP) than with clinic BP, and whether the correlation between home BP and ECG-LVH increases with the number of home measurements performed. We studied a representative sample of the general adult population (1989 subjects 45-74 years of age) in Finland. Subjects included in the study underwent a clinical interview, electrocardiography and measurement of clinic BP (mean of two clinic measurements) and home BP (mean of 14 duplicate home measurements performed during 1 week). Home BP correlated significantly better than clinic BP with the Sokolow-Lyon voltage (home/clinic systolic: r=0.23/0.22, P=0.60; diastolic: r=0.17/0.12, P=0.009), Cornell voltage (systolic: r=0.30/0.25, P=0.004; diastolic: r=0.21/0.12, P<0.001) and Cornell product (systolic: r=0.30/0.24, P=0.001; diastolic r=0.22/0.14, P<0.001) criteria of ECG-LVH. The correlation between home BP and ECG-LVH increased slightly with the number of home measurements, but even the mean of the initial two home BP measurements correlated equally well (systolic BP), or better (diastolic BP) with ECG-LVH than did clinic BP. In conclusion, home BP measurement allows us to obtain a large number of measurements that have a strong association with ECG-LVH. Our data support the application of home BP measurement in clinical practice.