Impaired artery elasticity predicts cardiovascular morbidity and mortality- A longitudinal study in the Vara-Skövde Cohort.

It is still debated whether arterial elasticity provides prognostic information for cardiovascular risk beyond blood pressure measurements in a healthy population. To investigate the association between arterial elasticity obtained by radial artery pulse wave analysis and risk for cardiovascular diseases (CVD) in men and women. In 2002-2005, 2362 individuals (men=1186, 50.2%) not taking antihypertensive medication were included. C2 (small artery elasticity) was measured using the HDI/Pulse Wave CR2000. Data on acute myocardial infarction or stroke, fatal or non-fatal, was obtained between 2002-2019. Cox- regression was used to investigate associations between C2 and future CVD, adjusting for confounding factors such as age, sex, systolic blood pressure, heart rate, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), LDL- cholesterol, CRP (C-Reactive Protein), alcohol consumption, smoking and physical activity. At baseline, the mean age of 46 ± 10.6 years and over the follow-up period, we observed 108 events 70 events in men [event rate: 5.9%], 38 in women [event rate: 3.2%]. In the fully adjusted model, and for each quartile decrease in C2, there was a significant increase in the risk for incident CVD by 36%. (HR = 1.36, 95% CI: 1.01-1.82, p = 0.041). The results were accentuated for all men (HR = 1.74, 95% CI: 1.21-2.50, p = 0.003) and women over the age of 50 years (HR = 1.70, 95% CI: 0.69-4.20). We showed a strong and independent association between C2 and CVD in men. In women after menopause, similar tendencies and effect sizes were observed.

Association between self-reported alcohol consumption and diastolic dysfunction: a cross-sectional study.

BACKGROUND AND OBJECTIVES: While alcohol consumption is associated with common risk factors for diastolic dysfunction the independent impact of low levels of alcohol consumption on this condition in a community setting is still unclear.Thus, the aim of this study was to explore this association in a representative population sample employing optimal echocardiographic techniques. DESIGN: Cross-sectional observational study in community-based population. SETTINGS, PARTICIPANTS AND METHODS: Participants between 30 and 75 years of age were consecutively invited to a physical examination, interview, conventional echocardiography, including Tissue Velocity Imaging. Diastolic dysfunction was defined according to the European Society of Cardiology criteria, excluding subjects with ejection fraction <45%, self-reported history of heart failure or atrial fibrillation on ECG. Self-reported alcohol intake using a validated questionnaire was categorised as no intake, low and medium-high intake. RESULTS: In total, 500 men and 538 women (mean age 55.4±13) were successfully examined. Diastolic dysfunction was identified in 16% (79/500) of the men and 13% (58/538) of the women. The multivariable adjusted model revealed a strong and independent association between alcohol intake and diastolic dysfunction. In fact, using no alcohol intake as reference, diastolic dysfunction was independently associated with alcohol consumption in a dose-dependent fashion; low consumption, OR 2.3 (95% CI 1.3 to 4.0) and medium-high consumption OR 3.1 (95% CI 1.6 to 6.2), respectively. CONCLUSION: There was a significant association between alcohol consumption and diastolic dysfunction starting already at low levels that was supported by a dose-dependent pattern. These results need confirmatory studies and are important in public health policies.

Sex hormone-binding globulin levels and development of hypertension in middle-aged men and women.

OBJECTIVE: To investigate the association between sex hormone-binding globulin (SHBG) levels, change in blood pressure and development of hypertension. METHODS: In a community-based study, we examined 2816 middle-aged participants with focus on cardiometabolic risk factors in 2002-2005. A representative sample of 1954 men and women was invited to follow-up in 2012-2014 and 1327 were included in a second study visit. Mean follow-up time was 9.7 years. Blood pressure was measured according to the guidelines from the seventh Joint National Committee of Hypertension, and new cases of hypertension were recorded. SHBG was measured at baseline. The association between SHBG, blood pressure and new cases of hypertension was investigated using linear regression analyses and logistic regression analyses after excluding individuals treated with blood pressure-lowering drugs. RESULTS: Mean SBP and DBP at follow-up was 123 and 72 mmHg, respectively, and mean increase from baseline was 5.8 and 2.9 mmHg. During the follow-up time, 167 new cases of hypertension (16.1%) were identified. One standard deviation (SD) increase in SHBG at baseline was inversely associated with the risk to develop hypertension at follow-up (OR = 0.74, 95% CI 0.58-0.95) in the fully adjusted model. Moreover, one SD increase in SHBG was associated with a decrease in mean SBP (delta = -1.5 mmHg, 95% CI - 2.2 to -0.8) and DBP (delta = - 1.0 mmHg, 95% CI - 1.5 to -0.4), after adjusting for covariates. CONCLUSION: SHBG levels are inversely associated with development of hypertension and change in blood pressure levels independent of major risk factors.

Plasma Galectin-4 Levels Are Increased after Stroke in Mice and Humans.

Epidemiological studies have associated plasma galectin-4 (Gal-4) levels with prevalent and incident diabetes, and with an increased risk of coronary artery disease. To date, data regarding possible associations between plasma Gal-4 and stroke are lacking. Using linear and logistic regression analyses, we tested Gal-4 association with prevalent stroke in a population-based cohort. Additionally, in mice fed a high-fat diet (HFD), we investigated whether plasma Gal-4 increases in response to ischemic stroke. Plasma Gal-4 was higher in subjects with prevalent ischemic stroke, and was associated with prevalent ischemic stroke (odds ratio 1.52; 95% confidence interval 1.01-2.30; p = 0.048) adjusted for age, sex, and covariates of cardiometabolic health. Plasma Gal-4 increased after experimental stroke in both controls and HFD-fed mice. HFD exposure was devoid of impact on Gal-4 levels. This study demonstrates higher plasma Gal-4 levels in both experimental stroke and in humans that experienced ischemic stroke.

Association between low internal health locus of control, psychological distress and insulin resistance. An exploratory study.

AIM: To assess the hypothesis that low internal health locus of control (IHLC) and psychological distress (PD) are associated with insulin resistance. MATERIALS AND METHODS: In 2002-2005, a random population sample of 2,816 men and women aged 30-74 years participated (76%) in two municipalities in southwestern Sweden. This study included 2,439 participants without previously known diabetes or cardiovascular disease. IHLC was measured by a global scale and PD was measured by the 12-item General Health Questionnaire. Insulin resistance was estimated using HOMA-ir. General linear models were used to estimate differences in HOMA-ir between groups with low IHLC, PD, and both low IHLC and PD, respectively. RESULTS: Five per cent (n = 138) had both PD and low IHLC, 62 per cent of participants (n = 1509) had neither low IHLC nor PD, 18 per cent (n = 432) had PD, and 15 per cent (n = 360) low IHLC. Participants with both low IHLC and PD had significantly higher HOMA-ir than participants with neither low IHLC nor PD (Δ = 24.8%, 95%CI: 12.0-38.9), also in the fully adjusted model (Δ = 11.8%, 95%CI: 1.5-23.0). Participants with PD had significantly higher HOMA-ir (Δ = 12%, 95%CI: 5.7-18.7), but the significance was lost when BMI was included in the model (Δ = 5.3%, 95%CI:0.0-10.8). Similarly, participants with low IHLC had significantly higher HOMA-ir (Δ = 10.1%, 95%CI: 3.5-17.0) but the significance was lost in the fully adjusted model (Δ = 3.5%, 95%CI: -1.9-9.3). CONCLUSIONS: Internal health locus of control (IHLC) and psychological distress (PD) were associated with insulin resistance. Especially individuals with both PD and low IHLC may need special attention.

Validation of a single question to measure internal health locus of control in Swedish primary care.

BACKGROUND: Behavioral risk factors are highlighted in the prevention of diabetes and cardiovascular disease. Screening for health locus of control could be a feasible way to better identify individuals who could benefit from preventive behavioral change interventions. The aim of the study was to investigate the correlation between a single question measuring internal health locus of control (IHLC) and the Multidimensional Health Locus of Control Scale (MHLC) and to assess how IHLC relates to the General Self-Efficacy scale (GSE) in a primary care setting. METHODS: Primary care patients, aged 18 and older, attending three primary care centers in southwest Sweden were consecutively asked to anonymously participate in the study. The patients were given a questionnaire and instructed to return the questionnaire in a sealed box in the waiting room. RESULTS: In all, 519 patients were included. The correlation between MHLC Internality and IHLC was weak (r = 0.21, p < 0.001). An increase of one point on the internality scale of the MHLC gave an odds ratio of 1.19 (95% CI 1.11-1.28) for reporting high IHLC, and thus a five-point increase gave a doubled likelihood, OR = 2.40, CI 1.67-3.46. The results for the other scales of the MHLC and GSE were similar. CONCLUSION: In this study, we found weak but statistically significant support for the single-question IHLC as a measure of internal health locus of control. Given that the correlation was weak, we recommend using the MHLC when possible.

Galectin-4 levels in hospitalized versus non-hospitalized subjects with obesity: the Malmö Preventive Project.

BACKGROUND: Obesity is strongly associated with the development of cardiovascular disease (CVD). However, the heterogenous nature of obesity in CVD-risk is still poorly understood. We aimed to explore novel CVD biomarkers and their possible association with presumed unhealthy obesity, defined as hospitalized subjects with obesity (HO). METHODS: Ninety-two proteins associated with CVD were analyzed in 517 (mean age 67 ± 6 years; 33.7% women) individuals with obesity (BMI ≥30 kg/m2) from the Malmö Preventive Project cohort, using a proximity extension array technique from the Olink CVD III panel. Individuals with at least one recorded hospitalization for somatic disease prior to study baseline were defined as HO phenotypes. Associations between proteins and HO (n = 407) versus non-hospitalized subjects with obesity (NHO, n = 110), were analyzed using multivariable binary logistic regression, adjusted for traditional risk factors. RESULTS: Of 92 analyzed unadjusted associations between biomarkers and HO, increased levels of two proteins were significant at a false discovery rate < 0.05: Galectin-4 (Gal-4) and insulin-like growth factor-binding protein 1 (IGFBP-1). When these two proteins were included in logistic regression analyses adjusted for age and sex, Gal-4 remained significant. Gal-4 was independently associated with the HO phenotype in multivariable logistic regression analysis (OR 1.72; CI95% 1.16-2.54). Post-hoc analysis revealed that this association was only present in the subpopulation with diabetes (OR 2.26; CI95% 1.25-4.07). However, an interaction analysis was performed, showing no significant interaction between Gal-4 and prevalent diabetes (p = 0.16). CONCLUSIONS: In middle-aged and older individuals with obesity, increased Gal-4 levels were associated with a higher probability of HO. This association was only significant in subjects with diabetes only, further implying a role for Gal-4 in diabetes and its complications.

High C-reactive protein is associated with increased risk of biochemical hypogonadism: a population-based cohort study.

Context: Obesity seems to decrease levels of testosterone. It is still unknown what role inflammation plays in the secretion of testosterone in men. Objective: The objective is to study the association between levels of C-reactive protein and testosterone and its role in predicting biochemical hypogonadism in men. Design: This was a longitudinal observational study between 2002 and 2014 in Sweden. Patients or other participants: At the first visit, a random population sample of 1400 men was included, and 645 men fulfilled a similar protocol at a 10-year follow-up visit. After exclusion, 625 men remained to be included in the final analyses. Main outcome measure(s): Serum concentrations of testosterone and C-reactive protein (CRP) were measured at both visits. Bioavailable testosterone was calculated. Biochemical hypogonadism was defined as total testosterone levels <8 nmol/L. Results: At the first visit and in the longitudinal analyses, a strong association was found between high levels of CRP and low levels of calculated bioavailable testosterone even after adjustments for age, waist-hip ratio, hypertension, smoking, type 2 diabetes, and leisuretime physical activity (B = -0.31, 95% CI -0.49 to -0.13, P = 0.001, B = -0.26, 95% CI -0.41 to -0.11, P = 0.001). Similarly, increase with one s. d. in CRP was associated with increased risk of having hypogonadism after adjustment in the final model (odds ratio (OR) 1.76, 95% CI 1.12-2.78, P = 0.015, OR 1.80, 95% CI 1.16-2.78, P =0.008). Conclusions: In this representative cohort of men in southwestern Sweden, high levels of CRP were longitudinally associated with low concentrations of calculated bioavailable testosterone and increased risk of biochemical hypogonadism.

Persisting prediabetic conditions and glomerular filtration rate - A longitudinal study.

The aim was to explore differences in the development of eGFR in persisting prediabetic conditions. This prospective study including 1327 individuals showed that eGFR decreased more in individuals with persisting IGT than in individuals with persisting IFG. Repeating OGTT and monitoring eGFR might improve the risk estimation in prediabetes.

Cardiometabolic Risk Factors and Endogenous Sex Hormones in Postmenopausal Women: A Cross-Sectional Study.

Context: It is uncertain which cardiovascular risk factors are associated with sex hormone levels in postmenopausal women. Objective: This work aimed to investigate the association between cardiometabolic risk factors and sex hormones in a cross-sectional, observational population study. Methods: In this Swedish population study, participants were physically examined from 2002 to 2004, and endogenous sex hormones were analyzed by liquid chromatography-tandem mass spectrometry. Women aged 55 years or older with estradiol levels below 20 pg/mL and not using any hormonal therapy were eligible for inclusion in the study (N = 146). Variable selection and bootstrap stability analyses were performed and linear regression models presented, with each of the 8 hormones as outcome variables. Results: Body mass index (BMI) was positively associated with estradiol (ß = 0.054, P < .001), but negatively associated with 17-α-hydroxyprogesterone (ß = -0.023, P = .028). Waist-to-hip ratio (WHR) was negatively associated with dihydrotestosterone (ß = -2.195, P = .002) and testosterone (ß = -1.541, P = .004). The homeostatic model assessment of insulin resistance was positively associated with androstenedione (ß = 0.071, P = .032), estradiol (ß = 0.091, P = .009), estrone (ß = 0.075, P = 0.009), and 17-α-hydroxyprogesterone (ß = 0.157, P = .001). Age was positively associated with testosterone (ß = 0.017, P = .042). C-reactive protein showed an inverse association with progesterone (ß = -0.028, P = .037). Lower low-density lipoprotein cholesterol was associated with higher estradiol levels (ß = -0.093, P = .049), whereas lower triglycerides were associated with higher concentrations of dihydrotestosterone (ß = -0.208, P = .016). Conclusion: In postmenopausal women, WHR was strongly inversely associated with androgens, while BMI was positively associated with estrogens.

The 10-year incidence of hypertension across blood pressure categories in a population-based cohort in southwestern Sweden.

BACKGROUND: To explore the determinants of incident hypertension, and especially the impact of baseline blood pressure categories, in a representative Swedish population. METHODS: A 10-year longitudinal study of residents aged 30-74. Blood pressures were measured and categorized according to ESH guidelines with optimal blood pressure < 120/80 mmHg, normal 120-129/80-84 mmHg, and high normal 130-139/85-89 mmHg. Incident hypertension was defined as ongoing treatment or three consecutive blood pressure readings ≥ 140/ ≥ 90 mmHg (one or both) at follow-up, while those with ≥ 140 and/or ≥ 90 mmHg at only one or two visits were labelled as unstable. After excluding subjects with hypertension, ongoing blood pressure lowering medication or a previous CVD event at baseline, 1099 remained for further analyses. RESULTS: Sixteen (2.6%) subjects with optimal baseline blood pressure had hypertension at follow up. Corresponding numbers for subjects with normal, high normal and unstable blood pressure were 55 (19.4%), 50 (39.1%) and 46 (74.2%), respectively. Compared with subjects in optimal group those in normal, high normal and unstable blood pressure categories had significantly higher risk to develop manifest hypertension with odds ratios OR and (95% CI) of 7.04 (3.89-12.7), 17.1 (8.88-33.0) and 84.2 (37.4-190), respectively, with adjustment for age, BMI and family history for hypertension. The progression to hypertension was also independently predicted by BMI (p < 0.001), however, not by age. CONCLUSIONS: Subjects with high normal or unstable blood pressure should be identified in clinical practice, evaluated for global hypertension risk and offered personalized advice on lifestyle modification for early prevention of manifest hypertension and cardiovascular disease.

Circulating endothelin-1 levels are positively associated with chronic kidney disease in women but not in men: a longitudinal study in the Vara-Skövde cohort.

BACKGROUND: The vasoconstricting peptide endothelin-1 (ET-1) is associated with endothelial dysfunction. The aim of this paper was to investigate whether circulating ET-1 levels predicts chronic kidney disease (CKD) in a prospective population study. METHODS: In 2002-2005, 2816 participants (30-74 years) were randomly selected from two municipalities in South-Western Sweden and followed up in a representative sample of 1327 individuals after 10 years. Endothelin-1 levels were assessed at baseline. Outcome was defined as CKD stage 3 or above based on eGFR < 60 mL/min/1.73m2. Those 1314 participants with successful analysis of ET-1 were further analyzed using binary logistic regression. RESULTS: At follow-up, 51 (8%) men and 47 (7,8%) women had CKD stage 3 and above. Based on levels of ET-1 the population was divided into quintiles showing that women in the highest quintile (n = 132) had a significantly increased risk of developing CKD during the follow up period (OR = 2.54, 95% CI:1.19-5.45, p = 0.02) compared with the other quintiles (1-4). The association was borderline significant after adjusted for age, current smoking, alcohol consumption, hypertension, diabetes, BMI, high- sensitive CRP and LDL-cholesterol (OR = 2.25, 95% CI:0.97-5.24, p = 0.06). No significant differences were observed between quintiles of ET-1 and development of CKD in men (NS). CONCLUSIONS: High levels of ET-1 are associated with development of CKD in women.

Effects of nutrition education using a food-based approach, carbohydrate counting or routine care in type 1 diabetes: 12 months prospective randomized trial.

INTRODUCTION: Evidence on the effects of structured nutrition education is weak in adults with type 1 diabetes mellitus (T1D) with moderately impaired glycemic control. Objective was to compare the effects of different types of nutrition education programs on glycemic control, cardiovascular risk factors, quality of life, diet quality and food choices in T1D. RESEARCH DESIGN AND METHODS: A 12 months randomized controlled study conducted at nine diabetes specialist centers with three parallel arms: (i) a food-based approach (FBA) including foods with low glycemic index or (ii) carbohydrate counting (CC) according to today's standard practice or (iii) individual sessions according to routine care (RC). The primary end point was difference in glycated hemoglobin A1c (HbA1c) between groups at 12 months. RESULTS: 159 patients were randomized (FBA: 51; CC: 52; RC: 55). Mean (SD) age 48.6 (12.0) years, 57.9% females and mean (SD) HbA1c level 63.9 (7.9) mmol/mol, 8% (0.7%). After 3 months, HbA1c improved in both FBA and CC compared with RC. However, there were no significant differences at 12 months in HbA1c; FBA versus RC (-0.4 mmol/mol (1.3), 0.04% (0.1%)), CC versus RC (-0.8 mmol/mol (1.2), 0.1% (0.1%)), FBA versus CC (0.4 mmol/mol (0.3), 0.04% (0.01%)). At 12 months, intake of legumes, nuts and vegetables was improved in FBA versus CC and RC. FBA also reported higher intake of monounsaturated and polyunsaturated fats compared with RC, and dietary fiber, monounsaturated and polyunsaturated fats compared with CC (all p values <0.05). There were no differences in blood pressure levels, lipids, body weight or quality of life. CONCLUSIONS: Nutrition education using an FBA, CC or RC is equivalent in terms of HbA1c and cardiovascular risk factors in persons with T1D with moderately impaired glycemic control. An FBA had benefits regarding food choices compared with CC and RC.

Longitudinal association between leisure-time physical activity and vascular elasticity indices.

AIM: We investigated the association between levels of leisure-time physical activity and vascular stiffness in a longitudinal observational study from a representative Swedish population. METHOD: A total of 2816 randomly selected individuals were examined at visit 1 (2002-2005, Men = 1400). After a mean follow-up of 9.7 ± 1.4 years, a representative sample of 1327 of the original participants were re-examined at visit 2. After excluding subjects with hypertension at baseline, 761 participants were included in the longitudinal analyses. Leisure-time physical (LTPA) activity was self-reported and dichotomized as high or low (level 3, 4 and level 1, 2, respectively). Large Arterial Elasticity Index (LAEI) and Small Arterial Elasticity Index (SAEI) were measured using the HDI/Pulse Wave™ CR2000. Multivariable general linear models were used to investigate the differences in changes SAEI and LAEI based on LTPA levels. RESULTS: At visit 1, and after adjustment for possible confounders, participants in the high LTPA group had better small artery elasticity (SAEI) (SAEI in low-level LTPA: 7.89 ± 0.11, SAEI in high-level LTPA: 8.32 ± 0.15, ΔSAEI: 0.42, CI: 0.07-0.78; p = 0.020). SAEI decreased between the two assessments (Visit 1: SAEI 8.01 ± 3.37 ml/mmHg; Δ SAEI: 1.4, CI 1.2-1.6, p < 0.001). Participants with a higher LTPA at visit 1 had significantly better SAEI at visit 2 (ΔSAEI: 0.44, CI 0.03-0.85, p = 0.037). No significant associations were observed between LAEI and LTPA after adjustments. CONCLUSIONS: High LTPA predicted higher small arterial compliance at visit 2 suggesting that positive effects of LTPA on arterial elasticity persists over time.

Report from an effort to prevent type 2 diabetes development in primary care.

BACKGROUND: In a clinical trial 2009-2012, individuals with prediabetes were randomised to a lifestyle intervention (LI) focused on physical activity or care as usual (CAU), with the aim of reducing development of type 2 diabetes (T2DM). At study termination after three years, there was a significantly less of an increase in insulin resistance in LI compared with the CAU group. The aim of this extended follow-up was to investigate whether positive results concerning metabolic variables remained five years after study termination. METHOD: All participants from the original study were contacted for a new follow-up with an oral glucose tolerance test, anthropometric measurements, blood pressure and blood samples. Questionnaires about lifestyle were completed. RESULTS: A total of 69 of the original 123 participants were examined, and personal data for another five participants were collected from the medical charts (n = 74). The LI group showed a decrease in diastolic blood pressure (-4 mmHg, CI 95% 0.8-6.8, p = 0.014) and body weight (-3 kg, CI 95% 1.2-4.9, p = 0.002) since base-line. Weight loss in the LI group was significantly greater compared with weight loss in the CAU group (-3 kg, CI 0.1-5.9, p = 0.044). Insulin resistance markers and incident T2DM were similar among the groups. CONCLUSION: Although without modifying the incidence of diabetes or the level of insulin resistance, a physical activity intervention may be used to induce sustainable weight change in subjects with prediabetes at the primary care level.

Association between body mass index and self-rated health: A Swedish population-based longitudinal study.

Aims: We aimed to investigate (a) the association between body mass index (BMI) and self-rated health (SRH) and (b) BMI's predicted value for SRH within a representative population in the Skaraborg Project. Methods: This was a longitudinal observational study. A random population of 2816 individuals were included in the study between 2002 and 2005, and a representative sample of these individuals were invited consecutively for a follow-up visit between 2012 and 2014. At follow-up, data from 1327 participants were collected concerning anthropometric variables, blood samples and validated questionnaires regarding lifestyle factors. Results: A significant inverse association was observed between BMI and SRH both at baseline and at follow-up, with all p-values for trend being ⩽0.001 in both men and women. This association was observed even after adjusting for confounders such as co-morbidity, age, sex, education, marital status and lifestyle factors. In addition, the longitudinal analyses showed that BMI at baseline was inversely associated with SRH at follow-up in both sexes (odds ratio (OR)=1.1, confidence interval (CI) 1.02-1.16, p=0.017 in men; and OR=1.1, CI 1.04-1.14, p=0.001 in women). These findings remained in participants whose weight increased (p=0.022) or was stable (p=0.004), while it was not seen in individuals who lost weight over the years (p=0.340). Conclusions: SRH is inversely associated with BMI in Swedish men and women. High BMI predicted low SRH from a longitudinal perspective, independent of co-morbidities, except for individuals who lost weight over the years. This knowledge emphasises the importance of an understanding and empathetic attitude towards these individuals.

C-reactive protein in traditional melanesians on Kitava.

BACKGROUND: Population-based levels of the chronic low-grade systemic inflammation biomarker, C-reactive protein (CRP), vary widely among traditional populations, despite their apparent absence of chronic conditions associated with chronic low-grade systemic inflammation, such as type 2 diabetes, metabolic syndrome and cardiovascular disease. We have previously reported an apparent absence of aforementioned conditions amongst the traditional Melanesian horticulturalists of Kitava, Trobriand Islands, Papua New Guinea. Our objective in this study was to clarify associations between chronic low-grade systemic inflammation and chronic cardiometabolic conditions by measuring CRP in a Kitava population sample. For comparison purposes, CRP was also measured in Swedish controls matched for age and gender. METHODS: Fasting levels of serum CRP were measured cross-sectionally in ≥ 40-year-old Kitavans (N = 79) and Swedish controls (N = 83). RESULTS: CRP was lower for Kitavans compared to Swedish controls (Mdn 0.5 mg/L range 0.1-48 mg/L and Mdn 1.1 mg/L range 0.1-33 mg/L, respectively, r = .18 p = .02). Among Kitavans, there were small negative associations between lnCRP for CRP values < 10 and total, low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol. Among Swedish controls, associations of lnCRP for CRP values < 10 were medium positive with weight, body mass index, waist circumference, hip circumference and waist-hip ratio and low positive with triglyceride, total cholesterol-HDL cholesterol ratio, triglyceride-HDL cholesterol ratio and serum insulin. CONCLUSIONS: Chronic low-grade systemic inflammation, measured as CRP, was lower among Kitavans compared to Swedish controls, indicating a lower and average cardiovascular risk, respectively, for these populations.

Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease.

AIMS: The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality. METHODS AND RESULTS: Plasma samples from 1713 individuals from the Swedish population-based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid-binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin-like growth factor-binding protein 2 (IGFB2), cathepsin D (CTSD), galectin-4 (GAL4), and paraoxonase-3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all-cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni-corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval: 1.17-1.41), CTSD (1.15-1.37), CD163 (1.09-1.30), IGFBP2 (1.05-1.30), and FABP4 (1.04-1.29)] and ACM and four proteins [GAL4 (1.38-1.56), CTSD (1.14-1.43), CD163 (1.09-1.36), and IGFBP2 (1.03-1.35)] with CVM. Three proteins [GAL4 (1.14-1.57), CTSD (1.12-1.50), and FABP4 (1.05-1.55)] were significantly associated with incident CE and two [GAL4 (1.03-1.54) and CTSD (1.01-1.46)] were associated with incident HF after adjusting for traditional risk factors including N-terminal pro-brain natriuretic peptide. CONCLUSIONS: In a general Swedish population, four proteins previously shown to be associated with diabetes were associated with ACM and CVM. Three proteins were associated with incident CE. Finally, GAL4 and CTSD displayed novel associations with incident HF and were the only proteins associated with all outcomes.