Search

Aim: To evaluate dyslipidemia as predictor of myocardial infarction (MI) in subjects with or without chronic kidney disease (CKD)., Methods: In 142,394 middle-aged Swedes referred for laboratory evaluation, glomerular filtration rates (GFR) were estimated using the Modification of Diet in Renal Disease study equation. CKD was defined as GFR 15-60 mL/min/1.73 m(2). Subjects were stratified into presence or absence of CKD, and lipid measures were related to MI using Cox's proportional hazards regression., Results: During 12 years of follow-up there were 5,466 MIs. The adjusted hazard ratio for MI for the highest versus the lowest quartile of the apolipoprotein (apo) B/apoA-1 ratio among individuals without CKD was 2.88 (95% confidence interval 2.54-3.26) and for those with CKD 3.35 (2.25-4.91). The corresponding estimates for the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio were 3.13 (2.78-3.52) and 3.54 (2.43-5.17), respectively. Receiver operator characteristics analyses showed an advantage in the prediction of MI for the apoB/apoA-1 ratio as compared to conventional lipids (P < 0.0001)., Conclusions: The ratio of apoB/apoA-1, the ratio of total cholesterol/HDL cholesterol, and non-HDL cholesterol were all strong predictors of myocardial infarction, both among subjects with and without renal dysfunction, with a possible advantage for the apoB/apoA-1 ratio.

Background and Aims: In contrast to lipoprotein components, few studies have analysed the importance of a combination of commonly available inflammatory markers as predictors of major cardiovascular events (MACE) in large healthy populations. We examined summary scores of inflammation and compared their predictive strength with that of lipoproteins in the Apolipoprotein MOrtality RISk (AMORIS) Study., Method and Results: Using data from AMORIS and the Swedish hospital discharge and mortality registers, a prospective cohort study of 65,050 subjects with mean follow-up time of 11.8 years, we studied the association between lipoproteins, inflammatory markers and risk of acute myocardial infarction (AMI), stroke and heart failure. An inflammatory score was measured as the number of inflammatory variables (white blood cell count, haptoglobin and in a subgroup CRP) in their upper quartile or as a continuous summary score. All analyses were conducted with multivariate Cox proportional hazards analysis. The inflammatory scores added predictive information over and above classical lipids such as total cholesterol and triglycerides. Compared to the apolipoprotein B (apoB)/apolipoprotein A-1 (apoA-1) ratio, a stronger marker of CVD risk than conventional lipids, the inflammatory score added some discrimination value measured by net reclassification improvement, but added more within higher risk strata. No statistically significant biological interaction was found between lipoproteins and inflammatory markers., Conclusion: The inflammation score and lipoproteins, including apoB and apoA-I, carry important and at least additive predictive information for risk of MACE. Routinely used markers of inflammation could be used in daily medical practice to assess cardiovascular risk., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The long-term trajectories of lipid and glucose levels in subjects who experience a major cardiovascular (CV) event at a young age has not been well studied. Our objective was to investigate lipid, lipoprotein, apolipoprotein (apo), and glucose levels in individuals experiencing a CV event before 50 years of age. Methods and findings: A first CV event [non-fatal myocardial infarction (MI), coronary revascularisation, or CV related death] before age 50 was recorded in 2,939 (cumulative incidence 1.2% in males and 0.3% in females) of 361,353 individuals included in the prospective Swedish AMORIS (Apolipoprotein-related MOrtality RISk) study with health examinations 1985–1996 and follow-up through 2011. In a nested case-control analysis, cases with a CV event were matched to randomly selected controls. Population risk factor trajectories were calculated up to 20 years prior to an event. Total cholesterol (TC), triglyceride (TG), and glucose levels were higher in cases than in controls as early as 20 years prior to the event with differences increasing over time. Low density lipoprotein, apoB, and the apoB/apoA-1 ratio were higher and increased over time, while HDL and apoA-1 were lower in cases compared to controls. The odds ratio was 2.5 (95% confidence interval 1.6–3.7) for TC ≥5 mmol/L and TG ≥1.7 mmol/L in cases versus controls. The adjusted population-attributable fractions including lipids, glucose, diabetes, smoking, hypertension, and obesity indicated that about 50% of CV events before age 50 may be associated with elevated lipid and glucose levels. Conclusions: Elevated TC, TG, LDL, apoB, and glucose levels and high apoB/apo A-1 ratio documented two decades before a CV event in subjects younger than 50 years may account for about half of CV events before age 50, which calls for early recognition and possibly treatment of modifiable CV risk factors in young individuals. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is associated with non-alcoholic fatty liver disease, which may progress to cirrhosis, a significant risk factor of hepatocellular carcinoma (HCC), the commonest malignant primary liver cancer (PLC). We investigated the association between the individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity), PLC and cirrhosis. A total of 509,436 participants from the Swedish AMORIS cohort, recruited between January 1985 and December 1996 (end-date December 2011), aged ≥20 with baseline triglycerides (TG), total cholesterol (TC), glucose and liver enzymes were included. Those with baseline benign liver tumours, PLC or cirrhosis were excluded. Multivariate Cox regression, adjusted for age, gender, socio-economic status, liver disease (excluding cirrhosis) and MetS factors were used to estimate the association with PLC and cirrhosis. There were 766 PLC and 2,775 cirrhosis cases over 13 years. Raised TG, low TC, raised glucose, diabetes and low HDL were associated with an increased risk of developing PLC and cirrhosis. ApoB/ApoA-I ratio were also associated with PLC, whilst low LDL, raised TG/HDL, low ApoA-I and low ApoB were associated with cirrhosis. Obesity was significantly associated with PLC but not cirrhosis. Raised TG, low TC, raised glucose and diabetes showed stronger associations with PLC in participants with cirrhosis but many participants developed PLC without cirrhosis. Individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity) were associated with an increased risk of developing PLC or cirrhosis. MetS components were more strongly associated with PLC with preceding cirrhosis history but many participants developed PLC without cirrhosis. [ABSTRACT FROM AUTHOR]

Objective: To assess the associations of blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolisms with the future risk of amyotrophic lateral sclerosis (ALS).Methods: In the Apolipoprotein-related MOrtality RISk study, we enrolled 636,132 men and women during 1985-1996 in Stockholm, Sweden, with measurements of serum glucose, total cholesterol, triglycerides, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Serum low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were either directly measured or calculated from total cholesterol, triglycerides, and apoA-I. The cohort was followed until the end of 2011. We used Cox models and mixed-effects models to, first, estimate the associations between these biomarkers and ALS incidence and, second, to assess the changes of these biomarkers during the 20 years before ALS diagnosis.Results: One-unit increase of LDL-C (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.02-1.27), apoB (HR = 1.68; 95% CI = 1.17-2.42), and apoB/apoA-I ratio (HR = 1.90; 95% CI = 1.29-2.78) was associated with a higher incidence of ALS. High glucose level (≥6.11mmol/L) was associated with a lower incidence (HR = 0.62; 95% CI = 0.42-0.93), whereas high LDL-C/HDL-C (≥3.50; HR = 1.50; 95% CI = 1.15-1.96) and high apoB/apoA-I (≥0.90 for men, ≥0.8 for women; HR = 1.41; 95% CI = 1.04-1.90) ratios were associated with a higher incidence. During the 10 years before diagnosis, ALS patients had increasing levels of LDL-C, HDL-C, apoB, and apoA-I, whereas gradually decreasing levels of LDL-C/HDL-C and apoB/apoA-I ratios.Interpretation: Alterations in the carbohydrate, lipid, and apolipoprotein metabolisms are associated with ALS risk and may serve as prodromal symptoms decades before ALS diagnosis. The imbalance between apoB and apoA-I as well as between LDL-C and HDL-C may be an etiological mechanism for ALS and needs to be further studied. Ann Neurol 2017;81:718-728. [ABSTRACT FROM AUTHOR]

Background: The lipid and glucose metabolisms are postulated as possible intermediary mechanisms in linking obesity and breast cancer (BC). Links between serum lipid and glucose biomarkers and BC risk has been observed in the Swedish Apolipoprotein MORtality RISk (AMORIS) cohort. We conducted a follow-up analysis including information on tumour characteristics.Methods: One thousand eight hundred twenty-four women diagnosed with BC, with serum biomarker levels of glucose, triglycerides, cholesterol (total, HDL, and LDL), and apolipoproteins A-1 and B recorded in a routine health check at baseline were included. BC severity was split into categories (good, moderate, and poor prognosis) based on ER status, TNM stage, and age at diagnosis. Proportional odds models were used to obtain odds ratios (ORs) and 95% confidence intervals (CI), with the interval time between baseline measurement and BC diagnosis accounted for.Results: Serum glucose and the ApoB/ApoA-1 ratio showed a non-statistically significant positive association with BC severity (proportional OR: 1.25 (95%CI: 0.92-1.70) for glucose (Conclusions: Despite the size and detail of data in AMORIS, we only found a modest positive association between serum levels of glucose, apoB/ApoA-1 and BC severity, suggesting that these factors are not the main players in linking obesity and BC aggressiveness. [ABSTRACT FROM AUTHOR]

To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I2 test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88-0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66-0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations. [ABSTRACT FROM AUTHOR]

Background: Both dietary and serum levels of inorganic phosphate (Pi) have been linked to development of cancer in experimental studies. This is the first population-based study investigating the relation between serum Pi and risk of cancer in humans.Methods: From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected all participants (> 20 years old) with baseline measurements of serum Pi, calcium, alkaline phosphatase, glucose, and creatinine (n = 397,292). Multivariable Cox proportional hazards regression analyses were used to assess serum Pi in relation to overall cancer risk. Similar analyses were performed for specific cancer sites.Results: We found a higher overall cancer risk with increasing Pi levels in men ( HR: 1.02 (95% CI: 1.00-1.04) for every SD increase in Pi), and a negative association in women (HR: 0.97 (95% CI: 0.96-0.99) for every SD increase in Pi). Further analyses for specific cancer sites showed a positive link between Pi quartiles and the risk of cancer of the pancreas, lung, thyroid gland and bone in men, and cancer of the oesophagus, lung, and nonmelanoma skin cancer in women. Conversely, the risks for developing breast and endometrial cancer as well as other endocrine cancer in both men and women were lower in those with higher Pi levels.Conclusions: Abnormal Pi levels are related to development of cancer. Furthermore, the in verse association between Pi levels and risk of breast, endometrial and other endocrine cancers may indicate the role of hormonal factors in the relation between Pi metabolism and cancer. [ABSTRACT FROM AUTHOR]

Background. Metabolic syndrome has been linked to an increased cancer risk, but the role of dyslipidaemia in gastrointestinal malignancies is unclear. We aimed to assess the risk of oesophageal, stomach, colon, and rectal cancers using serum levels of lipid components. Methods. From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected 540,309 participants (> 20 years old) with baseline measurements of total cholesterol (TC), triglycerides (TG), and glucose of whom 84,774 had baseline LDL cholesterol (LDL), HDL cholesterol (HDL), apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Multivariate Cox proportional hazards regression was used to assess glucose and lipid components in relation to oesophageal, stomach, colon, and rectal cancer risk. Results. An increased risk of oesophageal cancer was observed in persons with high TG (e.g. HR: 2.29 (95% CI: 1.42-3.68) for the 4th quartile compared to the 1st) and low LDL, LDL/HDL ratio, TC/HDL ratio, log (TG/HDL), and apoB/apoAI ratio. High glucose and TG were linked with an increased colon cancer risk, while high TC levels were associated with an increased rectal cancer risk. Conclusion. The persistent link between TC and rectal cancer risk as well as between TG and oesophageal and colon cancer risk in normoglycaemic individuals may imply their substantiality in gastrointestinal carcinogenesis. [ABSTRACT FROM AUTHOR]

Aims: Few studies have analysed the influence of lipoprotein components (LC) on the development of congestive heart failure (HF) in large healthy populations. We examined LC together with glucose, haptoglobin (Hp), and uric acid (UA) as risk factors for HF in the Apolipoprotein MOrtality RISk (AMORIS) study. We also explored the possible interaction between these factors and the apolipoprotein B to apolipoprotein A-1 ratio (apoB/apoA-1) in HF. [ABSTRACT FROM PUBLISHER]

The lipoprotein-related risk of coronary artery disease is determined principally by the balance between atherogenic lipoprotein particles, i.e., the lipoprotein that contain apolipoprotein-B (apo-B), and the antiatherogenic particles, i.e., high-density lipoprotein particles that contain apo-A-I. However, there is also considerable evidence that patients with predominantly small dense low-density lipoprotein (LDL) have more adverse clinical outcomes than do those with large buoyant LDL. The AMORIS study prospectively examined the relative importance of lipoprotein lipids versus apolipoproteins on the risk of fatal myocardial infarction in a large Swedish cohort. This updated analysis includes 69,029 men and 57,167 women who were followed for a mean of 10.3 years. Our objective was to determine whether LDL size as reflected by the LDL cholesterol/apo-B ratio added significant predictive power to apo-B or the apo-B/apo-A-I ratio. Although apo-A-I added significantly to the predictive power of apo-B, categorical and continuous multivariate analyses showed that this is not the case for LDL size. The strongest single lipoprotein-related risk factor was the apo-B/apo-A-I ratio. In conclusion, these results provide further confirmation of the importance of determining apo-B and apo-A-I in routine clinical practice. [Copyright &y& Elsevier]

Background: The apolipoprotein B (apoB)/apoA-l ratio represents the balance of proatherogenic and anti-atherogenic lipoproteins. The purpose of this study was to determine whether the apoB/apoA-l ratio was superior to any of the cholesterol ratios - total cholesterol/high-density lipoprotein cholesterol (TC/HDL- C), low-density lipoprotein cholesterol (LDL-C)/HDL-C and non-HDL-C/HDL-C - in predicting the risk of coronary disease. Moreover, we examined whether any lipids, lipoproteins or cholesterol ratios add significant predictive information beyond that provided by the apoB/apoA-l ratio. Methods: Plasma lipids, lipoproteins, apoB, and apoA-l were measured in 69,030 men and 57,168 women above 40 years of age. After a mean follow-up of 98 months, 1183 men and 560 women had died from a myocardial infarction in this prospective apolipoprotein-related mortality risk (AMORIS) study. Results: High apoB and a high apoB/apoA-l ratio were strongly related to increased coronary risk, while high apoA-l was inversely related to risk. The apoB/apoA-l ratio was superior to any of the choles- terol ratios in predicting risk. This advantage was most pronounced in subjects with LDL-C levels <3.6 mmol/l. Addition of lipids, lipoproteins or any cholesterol ratio to apoB/apoA-l in risk models did not further improve the strong predictive value of apoB/apoA-l. Conclusions: These results indicate that the apoB/apoA-l ratio is at present the best single lipoprotein- related variable to quantitate coronary risk. Given the additional advantages apolipoproteins possess -fasting samples are not required, apoB/apoA-l is a better index of the adequacy of statin therapy than LDL-C, and the measurement of apoB and apoA-l are standardized, whereas LDL-C and HDL-C are not - there would appear to be considerable advantage to integrating apolipoproteins into clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim was to investigate country or region of birth-specific prevalence and gender differences of diabetes in residents in Sweden, using Swedish-born men and women as referent. Methods: The Apolipoprotein MOrtality RISk (AMORIS) cohort was used (184,000 men and 151,453 women) aged between 20 and 80 years, with data from the CALAB laboratory, Stockholm, 1985–1996. Diabetes was defined as fasting glucose ≥7.0mmol/L or a hospital diagnosis of diabetes. Country of birth was obtained by linkage to Swedish Censuses 1970–1990. Standardized prevalence rate ratios (SPRR) with 95% confidence intervals (95% CI) were estimated. Results: Five groups of women and one group of men had a significantly higher prevalence than Swedish-born (based on SPRR): women born in Iraq (6.0 (95% CI 1.3–28.9)), North Africa (6.9 (95% CI 3.1–15.3)), South Asia (3.1 (95% CI 1.0–10.0)), Syria (5.3 (95% CI 1.8–16.0)), Turkey (3.7 (95% CI 1.2–10.9)) and men born in other Middle Eastern countries (2.3 (95% CI 1.0–5.5)). Swedish-born men had a higher age-standardized prevalence of diabetes (3.9%) than Swedish born women (2.5%). A higher prevalence among men was also seen in other Western countries. In contrast, a higher age-standardized prevalence among women was observed in immigrants from Turkey (8.9% vs. 3.1%, p <0.001), Syria (13.1% vs. 4.0%, p =0.002), and North Africa (16.8% vs. 6.6%, p <0.001). Conclusion: Female immigrants to Sweden from Iraq, North Africa, South Asia, Syria, and Turkey have an increased prevalence of diabetes of substantial public health concern. [Copyright &y& Elsevier]

Abstract: Objective: A complete lipoprotein profile requires measurement of the major plasma apolipoproteins—apoB and apoA-I—in addition to measurement of the major plasma and lipoprotein lipids. The objective of this study was to demonstrate the additional information that can be acquired by comparing the major plasma lipids and apolipoproteins amongst adult male and female Swedes, Iranians and Americans. Methods: Data on Iranians were derived from the Isfahan Healthy Heart Program, a prospective community-based sample of 12,103 individuals >20 years of age. Data on Swedes were derived from the AMORIS study, a prospective epidemiological study of 173,629 subjects. Data on Americans were derived from the NHANES III, data bank, which is designed to be representative of the adult American population. Lipids were measured by conventional methods. ApoB and apoA-I were measured by IFCC/WHO standardized methods. Results and Conclusions: There is a complex pattern of differences amongst the cultures. There are also important similarities in the differences between the genders. Swedes have the highest levels of LDL-C (3.77mmol/L), apoB (1.27g/L) and HDL-C (1.53mmol/L) but the lowest levels of triglyceride (1.47mmol/L for the Swedes vs. 1.55mmol/L and 1.93mmol/L for the Americans and Iranians, respectively, all p <0.001). Americans have higher levels of LDL-C than Iranians (3.26mmol/L vs. 3.09mmol/L, p <0.001) but lower levels of apoB (1.04g/L vs. 1.14g/L, p <0.001). The absolute values for both HDL-C and apoA-I are higher in females than males of all three cultures throughout the population distribution. The levels of the atherogenic lipoproteins peak between 30 and 40 in males but continue to rise in females. The apoB/apoA-I ratio is highest in the Swedes (0.92, p <0.001) but similar in the Americans and Iranians (0.81 and 0.80, respectively, p NS). By contrast, the TC/HDL-C ratio is highest in the Iranians, intermediate in the Americans and lowest in the Swedes (4.41 vs. 4.36 vs. 4.22, all p <0.001). These data provide further evidence that complete characterization of lipoproteins requires measurement of apoB and apoA-I as well as lipoprotein lipids and that the changes in plasma lipoproteins over time differ between the genders. [Copyright &y& Elsevier]