Risk of venous thromboembolism in relation to high physical activity level in men over 27 year follow up.

Venous thromboembolism (VTE) is the third most common type of cardiovascular disease. An association between high level of physical activity (PA) and the onset of VTE has been found in some, but not all previous studies. We aim to study the association between PA-level and VTE in a cohort of men with updated data on PA levels at four occasions. We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM) study initiated in 1970, a study of men at age 50 years (n = 2,294 at baseline) examined on leisure time PA by questionnaire and traditional cardiovascular risk factors. Examinations were repeated at ages 60, 70, and 77, and follow-up was completed after a median time of 33 years. Cox regression analysis with hazard ratios (HRs) using updated covariates for PA and risk factors was performed on the association of PA levels with incident VTE, with adjustments for established cardiovascular risk factors (systolic blood pressure, LDL- and HDL-cholesterol, BMI, diabetes, and smoking). Totally 186 men experienced a VTE during follow-up of 68,263 person-years at risk. Individuals with the highest PA level had an increased relative risk of VTE, adjusted HR, 2.22 (95% CI 1.05-4.67), when compared to individuals with the lowest level of PA. In this cohort of men with a follow-up of 27 years, the risk of VTE was increased at the highest PA level. Findings indicate that there could be an increased VTE risk with higher PA level including strenuous activities.

Medicines postpartum in Sweden and coverage in Janusmed Breastfeeding.

PURPOSE: The purpose of this article is (1) to investigate which medicines are prescribed and dispensed to women the first 6 months postpartum, (2) to identify medicines dispensed postpartum but not recommended during breastfeeding, and (3) to find medicines commonly dispensed postpartum, but not currently included in Janusmed Breastfeeding. METHODS: In this register-based cohort study covering births between January 2017 and August 2019, the Swedish Medical Birth Register (MBR), the Prescribed Drug Register, and Janusmed Breastfeeding were linked to identify medicines dispensed to women during the first 6 months postpartum, and how they are covered and classified in Janusmed Breastfeeding. RESULTS: During the first 6 months postpartum, 66% of women purchased at least one prescription medicine from the pharmacy. The most common medicines were contraceptive agents, analgesics, antibiotics, and glucocorticoids. A third of the 30 most commonly dispensed medicines have no information available about the safety of use in breastfeeding. The most dispensed medicines, where the database advises against use in breastfeeding, included several antitussive agents, a local anaesthetic, and several gestagens. The most commonly dispensed medicines not covered by the Janusmed Breastfeeding were medicines for dry eyes, for assisted reproduction, and HIV. CONCLUSION: Prescribed medicines compatible with breastfeeding are more common during the first 6 months postpartum than medicines not compatible with breastfeeding, but medicines which lack evidence for safety in breastfeeding are still commonly used.

Plasma perfluoroalkyls are associated with decreased levels of proteomic inflammatory markers in a cross-sectional study of an elderly population.

Perfluoroalkyl substances (PFAS) have been linked to immunotoxicity in experimental studies. Although PFAS exposure is associated with altered immune response in epidemiological studies of children, it is less known whether this is observed also in elderly adults. Eight PFAS and 86 proteins were measured in plasma from 965 elderly individuals from Sweden (all aged 70, 50% women). PFAS were measured using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry. Proteins were measured using a multiplex proximity extension assay (PEA) and covered among others inflammatory marker proteins such as monocyte chemoattractant proteins, tumor necrosis factors, and interleukins. We examined cross-sectional associations using multivariable linear regression at two levels of adjustment. We observed significant decreases in levels of 24 proteins in relation to a ln-unit increase in PFAS concentrations following adjustment for sex, sample storage time in freezer, and correction for multiple testing. Associations of PFAS and hepatocyte growth factor (HGF) and macrophage colony-stimulating factor 1 (CSF-1) remained significant (p-value <0.05) following full covariate adjustment for smoking, exercise habits, education, energy, and alcohol intake, body mass index (BMI), glomular filtration rate (GFR) as well as corticoid- and COX-inhibitor treatment. CSF-1 was inversely associated with perfluorohexane sulfonic acid (PFHxS) ß: -0.08: 95% confidence interval (CI); -0.13, -0.02), perfluorooctanoic acid (PFOA) ß: -0.04: 95% CI; -0.07, -0.006, perfluorononanoic acid (PFNA) ß: -0.04: 95% CI; -0.08, -0.003, perfluorodecanoic acid (PFDA) ß: -0.03: 95% CI; -0.06, -0.003, and perfluoroundecanoic acid (PFUnDA) ß: -0.05: 95% CI; -0.08, -0.02. The magnitude and direction of PFAS vs protein relationships were similar also for HGF. Our findings implicate PFAS exposure with decreased levels of proteomic markers of inflammation in elderly humans.

Using proximity extension proteomics assay to discover novel biomarkers associated with circulating leptin levels in patients with type 2 diabetes.

We aimed to discover novel associations between leptin and circulating proteins which could link leptin to the development of cardiovascular disease in patients with type 2 diabetes (T2DM). In a discovery phase, we investigated associations between 88 plasma proteins, assessed with a proximity extension assay, and plasma leptin in a cohort of middle-aged patients with T2DM. Associations passing the significance threshold of a False discovery rate of 5% (corresponding to p < 0.0017) were replicated in patients with T2DM in an independent cohort. We also investigated if proteins mediated the longitudinal association between plasma leptin and the incidence of major cardiovascular events (MACE). One protein, adipocyte fatty acid binding protein (A-FABP), was significantly associated with leptin in both the discovery phase [95% CI (0.06, 0.17) p = 0.00002] and the replication cohort [95% CI (0.12, 0.39) p = 0.0003]. Multiplicative interaction analyses in the two cohorts suggest a stronger association between A-FABP and leptin in men than in women. In longitudinal analyses, the association between leptin and MACE was slightly attenuated after adding A-FABP to the multivariate model. Our analysis identified a consistent association between leptin and A-FABP in two independent cohorts of patients with T2DM, particularly in men.Trial registration: ClinicalTrials.gov identifier NCT01049737.

Commonly used reference values underestimate oxygen uptake in healthy, 50-year-old Swedish women.

Cardiopulmonary exercise testing (CPET) is the gold standard among clinical exercise tests. It combines a conventional stress test with measurement of oxygen uptake (VO2 ) and CO2 production. No validated Swedish reference values exist, and reference values in women are generally understudied. Moreover, the importance of achieved respiratory exchange ratio (RER) and the significance of breathing reserve (BR) at peak exercise in healthy individuals are poorly understood. We compared VO2 at maximal load (peakVO2 ) and anaerobic threshold (VO2@AT ) in healthy Swedish individuals with commonly used reference values, taking gender into account. Further, we analysed maximal workload and peakVO2 with regard to peak RER and BR. In all, 181 healthy, 50-year-old individuals (91 women) performed CPET. PeakVO2 was best predicted using Jones et al. (100·5%), while SHIP reference values underestimated peakVO2 most: 112·5%. Furthermore, underestimation of peakVO2 in women was found for all studied reference values (P<0·001) and was largest for SHIP: women had 128% of predicted peakVO2 , while men had 104%. PeakVO2 was similar in subjects with peak RER of 1-1·1 and RER > 1·1 (2 328·7 versus 2 176·7 ml min-1 , P = 0·11). Lower BR (≤30%) related to significantly higher peakVO2 (P<0·001). In conclusion, peakVO2 was best predicted by Jones. All studied reference values underestimated oxygen uptake in women. No evidence for demanding RER > 1·1 in healthy individuals was found. A lowered BR is probably a normal response to higher workloads in healthy individuals.

Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort: gender-corrected and education-corrected normative data.

OBJECTIVES: To find cut-off values for different medial temporal lobe atrophy (MTA) measures (right, left, average, and highest), accounting for gender and education, investigate the association with cognitive performance, and to compare with decline of cognitive function over 5 years in a large population-based cohort. METHODS: Three hundred and ninety 75-year-old individuals were examined with magnetic resonance imaging of the brain and cognitive testing. The Scheltens's scale was used to assess visually MTA scores (0-4) in all subjects. Cognitive tests were repeated in 278 of them after 5 years. Normal MTA cut-off values were calculated based on the 10th percentile. RESULTS: Most 75-year-old individuals had MTA score ≤2. Men had significantly higher MTA scores than women. Scores for left and average MTA were significantly higher in highly educated individuals. Abnormal MTA was associated with worse results in cognitive test and individuals with abnormal right MTA had faster cognitive decline. CONCLUSION: At age 75, gender and education are confounders for MTA grading. A score of ≥2 is abnormal for low-educated women and a score of ≥2.5 is abnormal for men and high-educated women. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later. KEY POINTS: • Gender and education are confounders for MTA grading. • We suggest cut-off values for 75-year-olds, taking gender and education into account. • Males have higher MTA scores than women. • Higher MTA scores are associated with worse cognitive performance.

Targeted proteomic analysis of habitual coffee consumption.

BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health. OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418). METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay. RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10-3 ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), tumour necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (ß, -0.042 SD per cup of coffee, P = 0.028) and EpiHealth (ß, -0.025 SD per time of coffee, P = 0.004). The negative coffee-CHI3L association replicated in EpiHealth (ß, -0.07, P = 1.15 × 10-7 ), but not in ULSAM (ß, -0.034, P = 0.16). CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.

The association between p,p'-DDE levels and left ventricular mass is mainly mediated by obesity.

BACKGROUND AND OBJECTIVES: The pesticide metabolite p,p'-DDE has been associated with left ventricular (LV) mass and known risk factors for LV hypertrophy in humans and in experimental models. We hypothesized that the associations of p,p'-DDE with LV hypertrophy risk factors, namely elevated glucose, adiposity and hypertension, mediate the association of p,p'-DDE with LV mass. METHODS: p,p'-DDE was measured in plasma from 70-year-old subjects (n = 988) of the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). When these subjects were 70-, 75- and 80- years old, LV characteristics were measured by echocardiography, while fasting glucose, body mass index (BMI) and blood pressure were assessed with standard clinical techniques. RESULTS: We found that p,p'-DDE levels were associated with increased fasting glucose, BMI, hypertension and LV mass in separate models adjusted for sex. Structural equation modeling revealed that the association between p,p'-DDE and LV mass was almost entirely mediated by BMI (70%), and also by hypertension (19%). CONCLUSION: The obesogenic effect of p,p'-DDE is a major determinant responsible for the association of p,p'-DDE with LV mass.

Poor Response to Periodontal Treatment May Predict Future Cardiovascular Disease.

Periodontal disease has been associated with cardiovascular disease (CVD), but whether the response to the treatment of periodontal disease affects this association has not been investigated in any large prospective study. Periodontal data obtained at baseline and 1 y after treatment were available in 5,297 individuals with remaining teeth who were treated at a specialized clinic for periodontal disease. Poor response to treatment was defined as having >10% sites with probing pocket depth >4 mm deep and bleeding on probing at ≥20% of the sites 1 y after active treatment. Fatal/nonfatal incidence rate of CVD (composite end point of myocardial infarction, stroke, and heart failure) was obtained from the Swedish cause-of-death and hospital discharge registers. Poisson regression analysis was performed to analyze future risk of CVD. During a median follow-up of 16.8 y (89,719 person-years at risk), those individuals who did not respond well to treatment (13.8% of the sample) had an increased incidence of CVD ( n = 870) when compared with responders (23.6 vs. 15.3%, P < 0.001). When adjusting for calendar time, age, sex, educational level, smoking, and baseline values for bleeding on probing, probing pocket depth >4 mm, and number of teeth, the incidence rate ratio for CVD among poor responders was 1.28 (95% CI, 1.07 to 1.53; P = 0.007) as opposed to good responders. The incidence rate ratio among poor responders increased to 1.39 (95% CI, 1.13 to 1.73; P = 0.002) for those with the most remaining teeth. Individuals who did not respond well to periodontal treatment had an increased risk for future CVD, indicating that successful periodontal treatment might influence progression of subclinical CVD.

Effects of a common insecticide on wetland communities with varying quality of leaf litter inputs.

Chemical contamination of aquatic systems often co-occurs with dramatic changes in surrounding terrestrial vegetation. Plant leaf litter serves as a crucial resource input to many freshwater systems, and changes in litter species composition can alter the attributes of freshwater communities. However, little is known how variation in litter inputs interacts with chemical contaminants. We investigated the ecological effects resulting from changes in tree leaf litter inputs to freshwater communities, and how those changes might interact with the timing of insecticide contamination. Using the common insecticide malathion, we hypothesized that inputs of nutrient-rich and labile leaf litter (e.g., elm [Ulmus spp.] or maple [Acer spp.]) would reduce the negative effects of insecticides on wetland communities relative to inputs of recalcitrant litter (e.g., oak [Quercus spp.]). We exposed artificial wetland communities to a factorial combination of three litter species treatments (elm, maple, and oak) and four insecticide treatments (no insecticide, small weekly doses of 10 µg L-1, and either early or late large doses of 50 µg L-1). Communities consisted of microbes, algae, snails, amphipods, zooplankton, and two species of tadpoles. After two months, we found that maple and elm litter generally induced greater primary and secondary production. Insecticides induced a reduction in the abundance of amphipods and some zooplankton species, and increased phytoplankton. In addition, we found interactive effects of litter species and insecticide treatments on amphibian responses, although specific effects depended on application regime. Specifically, with the addition of insecticide, elm and maple litter induced a reduction in gray tree frog survival, oak and elm litter delayed tree frog metamorphosis, and oak and maple litter reduced green frog tadpole mass. Our results suggest that attention to local forest composition, as well as the timing of pesticide application might help ameliorate the harmful effects of pesticides observed in freshwater systems.

A genetic risk score is significantly associated with statin therapy response in the elderly population.

The ability of statins to strongly reduce low-density lipoprotein cholesterol (LDL-C) varies interindividually and is partially influenced by genetic variants. Based on a comprehensive analysis of 23 single nucleotide polymorphisms (SNPs) known to be associated with pharmacokinetics and dynamics of statins, we developed a genetic risk score to study its impact on the therapy outcome in elderly individuals under at least 5 years statin therapy. The study was performed in a population-based cohort of 1016 elderly individuals, which comprised 168 statin users investigated at age 75 and 80. Using random forest models, the major variants influencing LDL-C levels were summarized in a weighted GRS (wGRS). The wGRS was tested with lipid and glucose outcomes and validated in an independent population-based cohort including 221 statin users. Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. The wGRS was significantly associated with lower LDL-C at age 75 and 80. This association was replicated displaying similar results. GRS analysis is a powerful tool to evaluate the additive effects of genetic variants on statin response and to estimate the magnitude of LDL-C reduction to a considerable extent in the older population.

Lipophilic index, kidney function, and kidney function decline.

BACKGROUND AND AIMS: Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. METHODS AND RESULTS: Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended re-examination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction ≥30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m2 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m2, p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). CONCLUSIONS: A high LI was associated with lower kidney function, kidney function decline, and CKD progression.

Altered heart proteome in fructose-fed Fisher 344 rats exposed to bisphenol A.

Bisphenol A (BPA), is an artificial estrogen initially produced for medical purposes but is today widely used in polycarbonate plastics and epoxy resins. Exposure-related reproductive disorders have been found, but recently it has also been suggested that BPA may be involved in obesity, diabetes, myocardial hypertrophy and myocardial infarction in humans. To mimic a modern lifestyle, female rats were fed with fructose or fructose plus BPA (0.25mg/L drinking water). The myocardial left ventricle proteome of water controls, fructose-fed and fructose-fed plus BPA supplemented rats was explored. The proteome was investigated using nano-liquid chromatography tandem mass spectrometry and two-dimensional gel electrophoresis followed by matrix assisted laser desorption/ionization mass spectrometry identification. In total, 41 proteins were significantly altered by BPA exposure compared to water or fructose controls. Principal component analysis and cellular process enrichment analysis of altered proteins suggested increased fatty acid transport and oxidation, increased ROS generation and altered structural integrity of the myocardial left ventricle in the fructose-fed BPA-exposed rats, indicating unfavorable effects on the myocardium. In conclusion, BPA exposure in the rats induces major alterations in the myocardial proteome.

Association between levels of pentraxin 3 and incidence of chronic kidney disease in the elderly.

OBJECTIVE: Higher levels of the novel inflammatory marker pentraxin 3 (PTX3) predict cardiovascular mortality in patients with chronic kidney disease (CKD). Yet, whether PTX3 predicts worsening of kidney function has been less well studied. We therefore investigated the associations between PTX3 levels, kidney disease measures and CKD incidence. METHODS: Cross-sectional associations between serum PTX3 levels, urinary albumin/creatinine ratio (ACR) and cystatin C-estimated glomerular filtration rate (GFR) were assessed in two independent community-based cohorts of elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 768, 51% women, mean age 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 651, mean age 77 years). The longitudinal association between PTX3 level at baseline and incident CKD (GFR <60 mL(-1) min(-1) 1.73 m(-2) was also analysed (number of events/number at risk: PIVUS 229/746, ULSAM 206/315). RESULTS: PTX3 levels were inversely associated with GFR [PIVUS: B-coefficient per 1 SD increase -0.16, 95% confidence interval (CI) -0.23 to -0.10, P < 0.001; ULSAM: B-coefficient per 1 SD increase -0.09, 95% CI -0.16 to -0.01, P < 0.05], but not ACR, after adjusting for age, gender, C-reactive protein and prevalent cardiovascular disease in cross-sectional analyses. In longitudinal analyses, PTX3 levels predicted incident CKD after 5 years in both cohorts [PIVUS: multivariable odds ratio (OR) 1.21, 95% CI 1.01-1.45, P < 0.05; ULSAM: multivariable OR 1.37, 95% CI 1.07-1.77, P < 0.05]. CONCLUSIONS: Higher PTX3 levels are associated with lower GFR and independently predict incident CKD in elderly men and women. Our data confirm and extend previous evidence suggesting that inflammatory processes are activated in the early stages of CKD and drive impairment of kidney function. Circulating PTX3 appears to be a promising biomarker of kidney disease.

The Swedish CArdioPulmonary BioImage Study: objectives and design.

Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

Dietary acid load, kidney function, osteoporosis, and risk of fractures in elderly men and women.

SUMMARY: Because kidney dysfunction reduces the ability to excrete dietary acid excess, we hypothesized that underlying kidney function may have confounded the mixed studies linking dietary acid load with the risk of osteoporosis and fractures in the community. In a relatively large survey of elderly men and women, we report that dietary acid load did neither associate with DEXA-estimated bone mineral density nor with fracture risk. Underlying kidney function did not modify these null findings. Our results do not support the dietary acid-base hypothesis of bone loss. INTRODUCTION: Impaired renal function reduces the ability to excrete dietary acid excess. We here investigate the association between dietary acid load and bone mineral density (BMD), osteoporosis, and fracture risk by renal function status. METHODS: An observational study was conducted in 861 community-dwelling 70-year-old men and women (49% men) with complete dietary data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The exposure was dietary acid load as estimated from 7-day food records by the net endogenous acid production (NEAP) and potential renal acid load (PRAL) algorithms. Renal function assessed by cystatin C estimated glomerular filtration rate was reduced in 21% of the individuals. Study outcomes were BMD and osteoporosis state (assessed by DEXA) and time to fracture (median follow-up of 9.2 years). RESULTS: In cross-section, dietary acid load had no significant associations with BMD or with the diagnosis of osteoporosis. During follow-up, 131 fractures were validated. Neither NEAP (adjusted hazard ratios (HR) (95% confidence interval (CI)), 1.01 (0.85-1.21), per 1 SD increment) nor PRAL (adjusted HR (95% CI), 1.07 (0.88-1.30), per 1 SD increment) associated with fracture risk. Further multivariate adjustment for kidney function or stratification by the presence of kidney disease did not modify these null associations. CONCLUSIONS: The hypothesis that dietary acid load associates with reduced BMD or increased fracture risk was not supported by this study in community-dwelling elderly individuals. Renal function did not influence on this null finding.

Ambulatory blood pressure monitoring for risk stratification in obese and non-obese subjects from 10 populations.

Overweight clusters with high blood pressure (BP), but the independent contribution of both risk factors remains insufficiently documented. In a prospective population study involving 8467 participants (mean age 54.6 years; 47.0% women) randomly recruited from 10 populations, we studied the contribution of body mass index (BMI) to risk over and beyond BP, taking advantage of the superiority of ambulatory over conventional BP. Over 10.6 years (median), 1271 participants (15.0%) died and 1092 (12.9%), 637 (7.5%) and 443 (5.2%) experienced a fatal or nonfatal cardiovascular, cardiac or cerebrovascular event. Adjusted for sex and age, low BMI (<20.7 kg m(-2)) predicted death (hazard ratio (HR) vs average risk, 1.52; P<0.0001) and high BMI (> or = 30.9 kg m(-2)) predicted the cardiovascular end point (HR, 1.27; P=0.006). With adjustments including 24-h systolic BP, these HRs were 1.50 (P<0.001) and 0.98 (P=0.91), respectively. Across quartiles of the BMI distribution, 24-h and nighttime systolic BP predicted every end point (1.13 < or = standardized HR < or = 1.67; 0.046 < or = P<0.0001). The interaction between systolic BP and BMI was nonsignificant (P > or = .22). Excluding smokers removed the contribution of BMI categories to the prediction of mortality. In conclusion, BMI only adds to BP in risk stratification for mortality but not for cardiovascular outcomes. Smoking probably explains the association between increased mortality and low BMI.

The relationship between carotid intima-media thickness and global atherosclerosis.

BACKGROUND: The aim of this study was to investigate the relationship between (i) carotid intima-media thickness (CIMT) at baseline as well as (ii) change in CIMT over 5 years (ΔCIMT) and atherosclerotically induced luminal narrowing in non-coronary arterial territories assessed by whole-body magnetic resonance angiography (WBMRA). METHODS AND RESULTS: In subgroups of the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) study, US measurements of CIMT in the common carotid arteries were analysed at 70 and 75 years and ΔCIMT was calculated (n = 272). WBMRA, assessing arterial stenosis in five different territories by which also a total atherosclerotic score (TAS) was calculated, was performed at 70 years (n = 306). RESULTS: Carotid intima-media thickness in the carotid artery at baseline was correlated with TAS (P = 0.0001) when adjusted to a set of traditional risk factors for atherosclerosis, as well as to stenosis in two of the different investigated territories (aorta and lower leg, P = 0.013 and P = 0.004), but there was no significant correlation between ΔCIMT and TAS (P = 0.41). CONCLUSIONS: In the present study, CIMT, but not ΔCIMT over 5 years, in the carotid artery was related to overall stenoses in the body, as assessed by WBMRA. These findings support CIMT as a general marker for atherosclerosis.

Serum fatty acid patterns, insulin sensitivity and the metabolic syndrome in individuals with chronic kidney disease.

OBJECTIVES: The causes of the multiple metabolic disorders of individuals with chronic kidney disease (CKD) are not fully known. We investigated the relationships between dietary fat quality, the metabolic syndrome (MetS), insulin sensitivity and inflammation in individuals with CKD. SUBJECTS: Two population-based surveys were conducted in elderly Swedish individuals (aged 70 years) with serum cystatin C-estimated glomerular filtration rate <60 mL min(-1) /1.73 m2: the Uppsala Longitudinal Study of Adult Men (ULSAM) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) surveys. The present population comprised 274 men and 187 subjects (63% women) from the ULSAM and PIVUS cohorts, respectively. DESIGN: Factor analyses of serum fatty acids were used to evaluate dietary fat quality. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance (IR) and, in ULSAM, also by euglycaemic clamp. RESULTS: Factor analyses generated two fatty acid patterns of (i) low linoleic acid (LA)/high saturated fatty acid (SFA) or (ii) high n-3 polyunsaturated fatty acid (n-3 PUFA) levels. In both surveys, the low LA/high SFA pattern increased the odds of having MetS [adjusted odds ratio 0.60 [95% confidence interval (CI) 0.44-0.81] and 0.45 (95% CI 0.30-0.67) per SD decrease in factor score in the ULSAM and PIVUS surveys, respectively] and was directly associated with both IR and C-reactive protein. The n-3 PUFA pattern was not consistently associated with these risk factors. CONCLUSIONS: A serum fatty acid pattern reflecting low LA and high SFA was strongly associated with MetS, IR and inflammation in two independent surveys of elderly individuals with CKD. At present, there are no specific dietary guidelines for individuals with CKD; however, these findings indirectly support current recommendations to replace SFAs with PUFAs from vegetable oils.