Apolipoprotein MOrtality RISk Research Articles

Inorganic phosphate and the risk of cancer in the Swedish AMORIS study

BackgroundBoth 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.MethodsFrom 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.ResultsWe 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.ConclusionsAbnormal 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.

Iron metabolism and risk of cancer in the Swedish AMORIS study

ObjectivesPre-clinical studies have shown that iron can be carcinogenic, but few population-based studies investigated the association between markers of the iron metabolism and risk of cancer while taking into account inflammation. We assessed the link between serum iron (SI), total-iron binding capacity (TIBC), and risk of cancer by levels of C-reactive protein (CRP) in a large population-based study (n = 220,642).MethodsFrom the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected all participants (>20 years old) with baseline measurements of serum SI, TIBC, and CRP. Multivariate Cox proportional hazards regression was carried out for standardized and quartile values of SI and TIBC. Similar analyses were performed for specific cancers (pancreatic, colon, liver, respiratory, kidney, prostate, stomach, and breast cancer). To avoid reverse causation, we excluded those with follow-up <3 years.ResultsWe found a positive association between standardized TIBC and overall cancer [HR 1.03 (95 % CI 1.01–1.05)]. No statistically significant association was found between SI and cancer risk except for postmenopausal breast cancer [HR for standardized SI 1.09 (95 % CI 1.02–1.15)]. The association between TIBC and specific cancer was only statistically significant for colon cancer [i.e., HR for standardized TIBC: 1.17 (95 % CI 1.08–1.28)]. A borderline interaction between SI and levels of CRP was observed only in stomach cancer.ConclusionsAs opposed to pre-clinical findings for serum iron and cancer, this population-based epidemiological study showed an inverse relation between iron metabolism and cancer risk. Minimal role of inflammatory markers observed warrants further study focusing on developments of specific cancers.

Country of birth-specific and gender differences in prevalence of diabetes in Sweden

ObjectiveThe 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. MethodsThe 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. ResultsFive 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). ConclusionFemale immigrants to Sweden from Iraq, North Africa, South Asia, Syria, and Turkey have an increased prevalence of diabetes of substantial public health concern.

Serum Glucose and Fructosamine in Relation to Risk of Cancer

BackgroundImpaired glucose metabolism has been linked with increased cancer risk, but the association between serum glucose and cancer risk remains unclear. We used repeated measurements of glucose and fructosamine to get more insight into the association between the glucose metabolism and risk of cancer.MethodsWe selected 11,998 persons (>20 years old) with four prospectively collected serum glucose and fructosamine measurements from the Apolipoprotein Mortality Risk (AMORIS) study. Multivariate Cox proportional hazards regression was used to assess standardized log of overall mean glucose and fructosamine in relation to cancer risk. Similar analyses were performed for tertiles of glucose and fructosamine and for different types of cancer.ResultsA positive trend was observed between standardized log overall mean glucose and overall cancer risk (HR = 1.08; 95% CI: 1.02–1.14). Including standardized log fructosamine in the model resulted in a stronger association between glucose and cancer risk and aninverse association between fructosamine and cancer risk (HR = 1.17; 95% CI: 1.08–1.26 and HR: 0.89; 95% CI: 0.82–0.96, respectively). Cancer risks were highest among those in the highest tertile of glucose and lowest tertile of fructosamine. Similar findings were observed for prostate, lung, and colorectal cancer while none observed for breast cancer.ConclusionThe contrasting effect between glucose, fructosamine, and cancer risk suggests the existence of distinct groups among those with impaired glucose metabolism, resulting in different cancer risks based on individual metabolic profiles. Further studies are needed to clarify whether glucose is a proxy of other lifestyle-related or metabolic factors.

Serum calcium and incident and fatal prostate cancer in the Swedish AMORIS study

Observational studies have shown a positive association between intake of dairy products as well as serum levels of calcium and prostate cancer (PCa) risk. We studied the association between serum calcium and PCa while also accounting for levels of albumin, a protein to which calcium is bound. A cohort based on 196,022 men with baseline information on calcium (mmol/L) and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk study. Age-stratified multivariable Cox proportional hazard models were used to analyze associations between calcium and incident and fatal PCa risk. A total of 6,353 men were diagnosed with PCa and 731 died of PCa during mean follow-up of 12years. A weak negative association was found between levels of calcium or albumin-corrected calcium and PCa risk (HR for quartiles of albumin-corrected calcium: 0.95 (0.89-1.02), 0.93 (0.86-1.00), and 0.91 (0.85-0.98) for the 2nd, 3rd, and 4th quartile compared to the 1st; p for trend: 0.012). BMI did not affect these findings. No association was found between calcium levels and fatal PCa. A positive association between Ca and death was observed when censoring for PCa [HR per SD: 1.14 (1.13-1.16)]. The weak negative association between Ca and PCa risk is likely explained by the relation between Ca and death. This illustrates the need to handle competing risks when defining whether Ca is involved in PCa etiology or whether it acts as a marker of other metabolic events in the causal pathway.

Serum calcium and incident and fatal prostate cancer in the Swedish AMORIS study.

36 Background: Many observational studies have shown a positive association between intake of dairy products and prostate cancer (PCa) risk. From a biological point of view it is of interest to study this association as bone was recently shown to be a positive regulator of male fertility which suggests that regulation of bone remodeling and reproduction are linked. Since androgens promote cell proliferation and inhibit prostate cell death, it is possible that calcium (Ca) is linked to PCa risk via its link with the reproductive system. We studied the association between serum Ca and PCa while also accounting for levels of albumin, a protein to which Ca is bound. Methods: A cohort based on 192,183 men with baseline information on Ca (mmol/L) and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk (AMORIS) study. Age-stratified multivariable Cox proportional hazard models were used to analyze associations between Ca and incident and fatal PCa risk. All models were adjusted for fasting status, glucose levels, socio-economic status, season at time of Ca measurement, Charlson comorbidity index, and history of fractures. Results: A 6,202 men were diagnosed with PCa and 672 died of PCa during mean follow-up of 12 years. A weak negative association was found between PCa risk and Ca (HR per SD: 0.97 (95%CI: 0.95-1.00)). A similar association was also found between albumin-corrected Ca and PCa risk (HR: 0.96 (0.89-1.03), 0.94 (0.87-1.01), and 0.92 (0.86-0.99) for the 2nd, 3rd, and 4th quartile compared to the 1st; P for trend: 0.02). No association was found with fatal PCa, nor was there effect-modification by overweight. A strong positive association between Ca and death was observed when censoring for PCa (HR per SD: 1.13 (95%CI: 1.12-1.15)). Conclusions: Serum levels of Ca were weakly negatively associated with PCa risk in our study when adjusted for age and history of comorbidities and fractures. A negative association between Ca and PCa risk is likely explained by the strong relation between Ca and non-PCa death. These competing risks need to be handled in order to define whether Ca is causally involved in PCa aetiology or whether it only acts a marker of other metabolic events in the causal pathway.

Serum Lipids and the Risk of Gastrointestinal Malignancies in the Swedish AMORIS Study

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/apoA-I 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.

The interplay between lipid profiles, glucose, BMI and risk of kidney cancer in the Swedish AMORIS study

With exception of cholesterol and total fat intake, associations between lipid biomarkers and kidney cancer have not often been researched. We aimed to assess possible links between lipid profiles and kidney cancer risk in a large prospective cohort study, while also taking into account glucose levels and BMI. A cohort based on 542,924 persons with baseline information on glucose, triglycerides (TGs), total cholesterol (TC) and creatinine was selected from the Swedish Apolipoprotein Mortality Risk study. A subgroup of 85,621 also had baseline measurements of HDL, LDL, apolipoprotein A-I and apoB. Multivariate Cox proportional hazard models were used to analyze associations between quartiles and dichotomized values of these lipid components and kidney cancer risk. During a mean follow-up of 13 years, 958 persons developed kidney cancer. TGs were the only lipid component for which a statistically significant association was found with kidney cancer risk when using both quartiles and a clinical cutoff (hazard ratio: 1.25 (95% CI: 0.99-1.60), 1.29 (1.01-1.66) and 1.66 (1.30-2.13) for the 2nd, 3rd and 4th quartile, compared to the 1st, with p-value for trend: <0.001). The association remained after exclusion of the 95% percentile of TG. Quartiles of glucose were also positively associated with kidney cancer risk, whereas quartiles of TC were negatively associated with kidney cancer risk. This detailed analysis of lipid components only showed a consistent relation between TG levels and kidney cancer risk. Further mechanistic studies are required to assess links between lipid abnormalities and kidney cancer.

High blood hemoglobin concentration as risk factor of major atherosclerotic cardiovascular events in 114,159 healthy men and women in the Apolipoprotein MOrtality RISk study (AMORIS)

Background. Few studies have tested differences in relationships between hemoglobin (Hb) and long-term risk of major cardiovascular diseases according to age and gender in healthy subjects as opposed to anemia.Aims. Such relationships were examined and risk-tested in relation to Hb values in the Apolipoprotein MOrtality RISk (AMORIS) Study.Methods. Using data from AMORIS and the Swedish hospital discharge and mortality registers, a prospective cohort study of 114,159 subjects with mean follow-up of 11.8 years, the association between Hb and risk of acute myocardial infarction (AMI), ischemic stroke (IS), and congestive heart failure (CHF) by Cox regression analysis according to age and gender was studied.Results. Elevated Hb levels were associated to acute myocardial infarction (AMI) (HR 1.10 (1.06–1.13) per SD change), mostly confined to men and younger subjects but with greater sex similarity trends for CHF. Slightly increased risks were seen for the lowest Hb levels in the elderly and in females. IS risk was positively and more linearly associated to Hb.Interpretation. In AMORIS the highest AMI and CHF risks were found in the upper region of the distribution, but different shapes of relationships according to age and gender were found. IS associated positively with Hb. Key words:

Low levels of apolipoprotein A-I and HDL are associated with risk of prostate cancer in the Swedish AMORIS study

A detailed analysis of lipid profiles, using apolipoproteins, has not yet been conducted for prostate cancer (PCa). Since several etiological pathways have been proposed for PCa and lipids, we aimed to study this in a large Swedish cohort with 1,469 primary prostate cancers. A cohort (n = 69,735) of all men aged 35 years or older, whose levels of triglycerides (TG) (mmol/L), total cholesterol (mmol/L), glucose (mmol/L), LDL (mmol/L), HDL (mmol/L), apoB (g/L), and apoA-I (g/L) were measured at baseline, was selected from the Apolipoprotein MOrtality RISk (AMORIS) database. About 2,008 men developed PCa. Multivariate Cox proportional hazard models were used to analyze associations between lipid components and PCa. ApoA-I and HDL were inversely associated with PCa risk (e.g., HR for HDL: 0.93 (95% CI: 0.81-1.07), 0.88 (0.76-1.01), 0.81 (0.70-0.94), for second, third, and fourth quartiles compared with the first quartile; with p for trend: 0.004; HR for apoA-I: 1.00 (0.88-1.13), 0.93 (0.82-1.05), 0.88 (0.77-0.99),), for second, third, and fourth quartiles compared with the first quartile; with p for trend: 0.022). ApoB, LDL, and non-HDL were not associated with PCa risk. Our results show that low HDL and ApoA-I as well as increased lipid ratios are related to increased PCa risk. Experimental studies are required to tease out the underlying biological mechanisms linking these lipid components to PCa.

Gamma-glutamyltransferase and risk of cancer in a cohort of 545,460 persons – the Swedish AMORIS study

BackgroundApart from using gamma-glutamyltransferase (GGT) as a predictor of diabetes, cardiovascular and chronic kidney disease, some evidence suggests GGT as an indicator of cancer risk. We aimed to study the association between GGT and cancer in a large Swedish cohort with 37,809 primary cancers. MethodsIn a cohort of 545,460 persons (aged >20years) who had a measurement of GGT in the Apolipoprotein Mortality Risk (AMORIS) study, multivariate Cox proportional hazards regression was used to investigate categories of GGT (<18, 18–36,36–72, ⩾72U/L) in relation to cancer risk. Stratified analyses were conducted by gender, levels of alanine aminotransferase (ALT) (</⩾50U/L), glucose (</⩾6.11mmol/L) and triglycerides (</⩾1.71mmol/L). ResultsA positive association was found between categories of GGT and overall cancer risk (HR: 1.07 (95%CI: 1.04–1.09,), 1.18 (1.14–1.22), 1.32 (1.26–1.38) for the 2nd, 3rd and 4th categories compared to the 1st). Stratified analyses showed that for those with glucose ⩾6.11mmol/L, the association between GGT and risk of prostate, breast and liver cancer became stronger (e.g. HR for GGT ⩾72U/L and prostate cancer: 1.11 (0.98–1.26) and 1.35 (1.00–1.81) for glucose <6.11 and ⩾6.11mmol/L, respectively). With pancreatic cancer, the association with GGT was weaker for those with elevated glucose levels compared to those with normal levels. No effects of ALT or triglyceride levels on risk were found. ConclusionWe found evidence of associations between elevated GGT and risk of developing different cancers. The strength of this association may vary by glucose levels because hyperglycaemia can result in oxidative stress initiating damaging pathways of carcinogenesis.

Lipid profiles and the risk of kidney cancer in the Swedish AMORIS study.

342 Background: Since multiple epidemiologic studies showed a link between obesity and kidney cancer (KCa), the lipid metabolism is thought to play a role in development of KCa. With the exception of cholesterol and total fat intake, the association between changes in lipid biomarkers and KCa has not often been researched. We assessed the link between lipid profiles and KCa risk in a large prospective cohort study. Methods: A cohort based on 85,261 persons (&gt; 20 years old) with baseline measurements of glucose, triglycerides (TG), total cholesterol, HDL, LDL, apolipoprotein A-I and apoB was selected from the Swedish Apolipoprotein Mortality Risk (AMORIS) study. Multivariate Cox proportional hazards models were used to analyze associations between quartiles and dichotomized values of these lipid components and KCa risk. All models were adjusted for age, gender, socioeconomic status, fasting status, history of kidney disease prior to baseline (ICD9: 580-93), and glucose, cholesterol, and TG levels (depending on the covariate of interest). Results: During a mean follow-up of 12 years, 161 persons developed KCa (58% men). The mean age at baseline was 46 years. TG were the only lipid component for which a statistically significant association was found with risk of KCa (Hazard Ratio (HR): 1.05 (95%CI: 0.59-1.87), 1.77 (1.05-2.98), and 1.77 (1.04-3.02) for the second, third, and fourth quartile, compared to the first, with p-value for trend: 0.008). The lipid ratio of TG and HDL also showed a statistically significant positive association with risk of KCa (HR: 1.21 (0.71-2.08), 1.56 (0.94-2.58), and 1.92 (1.17-3.17) for the second, third, and fourth quartile, compared to the first, with p-value for trend: 0.004). No other associations were found between lipid components and KCa risk. Conclusions: This detailed analysis of lipid components and risk of KCa found a relation between levels of TG and KCa risk. In contrast to previous studies, we did not find an association between cholesterol levels and KCa risk. Lipid profiles based on the markers used in this study do not seem to reflect the etiological pathway that has previously been shown between obesity and KCa. Further mechanistic studies are required to assess the link between lipid deregulation and KCa. No significant financial relationships to disclose.

Association between Levels of C-Reactive Protein and Leukocytes and Cancer: Three Repeated Measurements in the Swedish AMORIS Study

To study levels of C-reactive protein (CRP) and leukocytes, as inflammatory markers, in the context of cancer risk. From the Apolipoprotein MOrtality RISk (AMORIS) study, we selected 102,749 persons with one measurement and 9,273 persons with three repeated measurements of CRP and leukocytes. Multivariate Cox proportional hazards regression was applied to categories of CRP (<10, 10-15, 15-25, 25-50, >50 g/L) and quartiles of leukocytes. An inflammation-based predictive score (IPS) indicated whether someone had CRP levels of more than 10 mg/L combined with leukocytes of more than 10×10(9)/L. Reverse causality was assessed by excluding those with less than 3, 5, or 7 years of follow-up. To analyze repeated measurements of CRP and leukocytes, the repeated IPS (IPSr) was calculated by adding the IPS of each measurement. In the cohort with one measurement, there was a positive trend between CRP and risk of developing cancer, with the lowest category being the 0.99 (0.92-1.06), 1.28 (1.11-1.47), 1.27 (1.09-1.49), and 1.22 (1.01-1.48) for the second to fifth categories, respectively. This association disappeared when excluding those with follow-up of less than 3, 5, or 7 years. The association between leukocytes and cancer was slightly stronger. In the cohort with repeated measurements, the IPSr was strongly associated with cancer risk: 1.87 (1.33-2.63), 1.51 (0.56-4.06), and 4.46 (1.43-13.87) for IPSr=1, 2, and 3 compared with IPSr=0. The association remained after excluding those with follow-up of less than 1 year. Our large, prospective cohort study adds evidence for a link between inflammatory markers and cancer risk by using repeated measurements and ascertaining reverse causality.

Risk of prostate cancer is not associated with levels of C‐reactive protein and other commonly used markers of inflammation

Most population-based studies studied the association between inflammation and prostate cancer (PCa) by assessing C-reactive protein (CRP). As these findings have shown inconsistent results, we aimed to also study different markers that have been commonly taken as indications of inflammation. A cohort based on four groups of men (n = 34,891), according to age at cohort entry (45, 55, 65 and 75 years), with measurements of glucose, triglycerides, total cholesterol, haptoglobin, albumin, hemoglobin and leukocytes were selected from the Apolipoprotein Mortality Risk database. A total of 17,937 men had measurements of non-high-sensitive CRP. Multivariate Cox proportional hazard models were used to analyze associations between inflammatory markers and PCa. A total of 49 of 12,063 men developed PCa in the age 45 group, whereas 207 of 9,940, 472 of 8,266 and 276 of 3,618 were diagnosed in the age 55, 65 and 75 groups, respectively. Mean follow-up time was 7.5 years (SD: 3.9). No markers showed an association with PCa risk, nor was there a trend by quartiles or an indication for different PCa risks by strata of hypercholesterolemia, hyperglycemia and hypertriglyceridemia status. The studied markers were not found to be associated with PCa risk. These null findings might be due to methodological issues; however, it is unlikely that strong and long-lasting associations between inflammation and PCa risk were missed as this was a large database with long follow-up. This indicates need for international consensus on appropriate inflammatory markers in the context of cancer that may be practically applied in large studies.

Prostate cancer risk in the Swedish AMORIS study

In a cohort including 5112 prostate cancer (pCa) patients, the authors investigated associations among triglycerides (TG), total cholesterol (TC), and pCa while taking into account glucose. A cohort (n = 200,660) based on 4 groups of men, according to age at cohort entry, with TG, TC, and glucose measurements was selected from the Apolipoprotein MOrtality RISk (AMORIS) database. Of these, 5112 men developed pCa. Multivariate Cox proportional hazard models were used to analyze associations among TG, TC, and pCa. Competing risks were assessed graphically. Age-stratified analyses for quartiles of TG, TC, and glucose showed a negative association between glucose and pCa risk (HR, 0.93; 95% CI, 0.86-1.01), 0.93 (0.86-1.01), 0.87 (0.81-0.94) for the second, third, and fourth quartiles compared with the first (P(trend) = .001). Stratified analysis by glucose levels (<6.11 or ≥ 6.11 mmol/L) showed a positive association between hypertriglyceridemia (TG ≥ 1.71 mmol/L) and pCa risk, when there were high glucose levels (HR, 1.23; 95% CI, 1.01-1.48). No association was found for hypercholesterolemia (TC ≥ 6.50 mmol/L). Competing risk analysis showed that protective effects of glucose were overestimated in conventional Cox proportional hazard models and strengthened positive findings between TG and pCa risk. The authors'; findings supported the hypothesis that factors of the glucose and lipid metabolism influence pCa risk. Competing risk assessment showed that it is important to take into account the long natural history and age distribution of pCa when interpreting results. The authors'; findings indicate another reason to fight the increasing prevalence of obesity and dyslipidemia.

Inflammatory markers, lipoprotein components and risk of major cardiovascular events in 65,005 men and women in the Apolipoprotein MOrtality RISk study (AMORIS)

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.

Lipids, myocardial infarction and ischaemic stroke in patients with rheumatoid arthritis in the Apolipoprotein-related Mortality RISk (AMORIS) Study

ObjectivesTo examine the rates of acute myocardial infarction (AMI) and ischaemic stroke (IS) and to examine the predictive value of total cholesterol (TC) and triglycerides (TG) for AMI and IS...

Immunoglobulin E and cancer: a meta-analysis and a large Swedish cohort study

We quantified associations between IgE and cancer in a meta-analysis and cohort study. Pubmed and Embase were searched to extract information using predefined inclusion criteria. In the Apolipoprotein MOrtality RISk (AMORIS) database, 24,820 persons had IgE measurements. Multivariate Cox proportional hazard models were used to analyze associations between IgE and cancer. Twenty-seven studies were reviewed from which seven case-control studies were included for analysis. The pooled relative risk (random effects model) was 0.97 (95% CI 0.86-1.09). Cell types of tumor origin (mesenchymal tissue or cells of the nervous system, lymphatic or hematopoietic tissue, and epithelium) modified the effect. In the AMORIS cohort, 862 persons developed cancer. Hazard ratios comparing quartiles of IgE were similar to the findings in the meta-analysis (HR 0.87 (95% CI 0.72-1.06); 0.94 (0.78-1.14); 0.90 (0.74-1.10) for the 2nd, 3rd, and 4th quartile compared to the 1st quartile), but there was no pattern by tumor origin. Both studies showed a weak inverse association between IgE and cancer, but a pattern by cancer type was only seen in the meta-analysis. Our findings suggest the need for prospective studies studying IgE and cancer. Measurements of IgE should be combined with other information, e.g., bio-banked samples containing other key immunological discriminators.

Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417 734 men and women in the Apolipoprotein MOrtality RISk study (AMORIS)

Few studies have simultaneously analysed the influence of elevated serum uric acid (UA) on acute myocardial infarction (AMI), ischaemic and haemorrhagic stroke (IS, HS) and congestive heart failure (CHF) in large healthy populations. We, here, examine UA as a risk factor for AMI, stroke and CHF by age and gender in the Apolipoprotein MOrtality RISk (AMORIS) Study. Prospective study (11.8 years, range 7-17) of fatal and nonfatal acute myocardial infarction, stroke and CHF through linkage with Swedish hospital discharge and mortality registers. Measurements of uric acid in 417,734 men and women from health check-ups in Stockholm area. There was a gradual increase in risk of AMI, stroke and CHF by increasing UA levels. Women had a stronger relationship between UA and both AMI and IS than men. Predictions of AMI were at least as powerful in the elderly as in the young, but not so for IS. Associations were markedly attenuated when adjusted for total cholesterol, triglycerides, hospital hypertension and diabetes status. The association between UA and HS was U-shaped in both genders. CHF was more strongly related to UA than AMI and stroke and less affected by the adjustment factors. Already moderate levels of UA appear to be associated with an increased incidence of AMI, stroke and CHF in middle-aged subjects without prior cardiovascular disease. These associations seem to increase gradually from lower to higher levels of UA. UA may be an important complementary indicator of cardiovascular risk in the general population.

Lipoprotein components and risk of congestive heart failure in 84 740 men and women in the Apolipoprotein MOrtality RISk study (AMORIS)

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. This was a prospective study of HF conducted over 11.8 years through links with the Swedish hospital discharge and mortality registers. Lipoprotein components and other risk factors were measured in 84 740 men and women during health check-ups. All LC were strongly associated with HF per gender adjusted for risk factors. Relationships were stronger for men than for women. Among LC the apoB/apoA-1 ratio was the strongest risk factor for HF in men and triglycerides (TG) in women, but differences in strength were not large. The Hp and UA added predictive information to that of the apoB/apoA-1 ratio, but glucose did not. There was no detectable interaction (synergistic effects) on relative risk between apoB/apoA-1 and these three additional factors. Over and above adjustment factors, the apoB/apoA-1 ratio and TG were the most predictive of the LC, but all LC were highly significantly related to the development of HF.