What has been found?

Cardiovascular disease

In an early study of 35,000 individuals with measurements of apoB, apoA-I and their ratio, we found a three to six-fold increase in the risk of acute myocardial infarction when cholesterol levels were ≥6.50 mmol/L and triglycerides were ≥2.30 mmol/L, as compared to those with lower values [1]. A key study was published in 2001 in Lancet, based on 175,553 men and women with a mean follow-up of 66.8 months [2]. The results indicated that apoB, apoA-I and especially the apoB/apoA-I ratio was highly predictive of fatal myocardial infarction and also more closely related to myocardial infarction than the measurements of LDL cholesterol. These observations were further confirmed [3-5] and also extended to other CV outcomes such as stroke [6, 7] and congestive heart failure [8-10].In these studies we also observed an association between the apoB/apoA-I ratio and inflammation markers such as uric acid [10], haptoglobin [11], leucocytes, and CRP [12]. These inflammation markers have further been shown to be associated with risk of CV outcomes including coronary heart disease, congestive heart failure and stroke [10-12].

In studies on diabetic subjects, we found that high levels of fructosamine, indicating degree of glycation, were closely related to HbA1c cross-sectionally and over time [13]. We also found that high levels of fructosamine is associated with an increased risk of myocardial infarction and all-cause mortality [14]. In patients with moderately reduced renal function, AMORIS data showed that their renal function was closely related to the apoB/apoA-I ratio and also an increased risk of myocardial infarction and stroke [15, 16]. The majority of these findings have been summarized and discussed in a review, while also taking into account other international results [17].

Cancer

We investigated glucose levels and risk of breast, endometrial, and ovarian cancer and showed that glucose levels below the diagnostic threshold for diabetes are associated with an increased risk not only of endometrial cancer, but also postmenopausal breast cancer [18]. We also studied the interplay between glucose, triglycerides, total cholesterol and risk of prostate, kidney, and gastro-intestinal cancers [19-21]. Finally, we assessed lipids and risk of breast, endometrial, and ovarian cancer [22,23], but only found a consistent positive association between triglycerides and endometrial cancer risk.

We have evaluated associations between levels of IgE and cancer risk in 24,820 persons [24]. We also reviewed different markers of inflammation, including C-reactive protein (CRP), albumin, and leukocytes [25]. One study was of particular interest as it used three repeated measurements of these markers [26]. More recently, we examined serum C-reactive protein (CRP), albumin, haptoglobin and white blood cells (WBC) in relation to breast cancer risk and survival. Findings showed systemic inflammation to be weakly associated to breast cancer risk and to impact survival [27]. Serum lactate dehydrogenase (LDH), another marker of inflammation and metabolic alterations in cancer, was studied in relation to survival following cancer diagnosis [28]. Worse overall survival in breast cancer patients was seen in those women with higher serum LDH measured within three years preceding diagnosis. We have also found an association between Gamma-GT and various forms of cancer beyond liver dysfunction tests (alanine aminotransferase) [29].

References in the AMORIS cohort paper

1. Walldius G, Jungner I, Kolar W, Holme I, Steiner E. High cholesterol and triglyceride values in Swedish males and females: increased risk of fatal myocardial infarction.

2. Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001 Dec 15;358(9298):2026-33.

3. Walldius G, Jungner I, Aastveit AH, Holme I, Furberg CD, Sniderman AD. The apoB/apoA-I ratio is better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk. Clin Chem Lab Med. 2004;42(12):1355-63.

4. Sniderman AD, Furberg CD, Keech A et al. Apolipoproteins versus lipids as indices of coronary risk and as targets for statin treatment. Lancet 2003;361:777-80.

5. Walldius G, Jungner I. Apolipoprotein B and apolipoprotein A-I: risk indicators of CHD and targets for lipid-modifying therapy. J Intern Med 2004;255:188-205.

6. Walldius G, Aastveit AH, Jungner I. Stroke mortality and the apoB/apoA-I ratio: results of the AMORIS prospective study. J Intern Med. 2006;259(3):259-66.

7. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G. Relationships between lipoprotein components and risk of ischaemic and haemorrhagic stroke in the Apolipoprotein MOrtality RISk study (AMORIS). J Intern Med. 2009;265(2):275-87.

8. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G. Inflammatory markers, lipoprotein components and risk of major cardiovascular events in 65,005 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). Atherosclerosis 2010;213(1):299-305.

9. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G. Lipoprotein components and risk of congestive heart failure in 84,740 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). Eur J Heart Fail. 2009;11(11):1036-42. doi:10.1093/eurjhf/hfp129.

10. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G. 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). J Intern Med. 2009;266(6):558-70.

11. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G. Haptoglobin and risk of myocardial infarction, stroke, and congestive heart failure in 342,125 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). Ann Med. 2009;41(7):522-32.

12. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G. Inflammatory markers, lipoprotein components and risk of major cardiovascular events in 65,005 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). Atherosclerosis. 2010;213(1):299-305.

13. Malmström H, Walldius G, Grill V, Jungner I, Gudbjörnsdottir S, Hammar N. Fructosamine Is a Useful Indicator of Hyperglycaemia and Glucose Control in Clinical and Epidemiological Studies – Cross-Sectional and Longitudinal Experience from the AMORIS Cohort. PLoS One 2014;9(10):1-9. e111463.

14. Malmström H, Walldius G, Grill V, Jungner I, Hammar N. Fructosamine is a risk factor for myocardial infarction and all-cause mortality – Longitudinal experience from the AMORIS cohort. Nutr Metabol Cardiovas Dis, Published On line, 26-JUL-2015. DOI information: 10.1016/j.numecd.2015.07.002.

15. Holtzmann M, Ivert T, Jungner I et al. Renal function assessed by two different formulas and incidence of myocardial infarction and death in middle-aged men and women. J Intern Med 2010;267:357-69.

16. Holzmann MJ, Aastveit A, Hammar N, Jungner I, Walldius G. Renal dysfunction increases the risk of ischemic and hemorrhagic stroke in the general population. Annals of Medicine, 2012;44:607-15.

17. Walldius G. Walldius G. The apoB/apoA-I Ratio is a Strong Predictor of Cardiovascular Risk, http://dx.doi.org/10.5772/47869. 2012, pages 95-148. Published in: Lipoproteins in Health and Diseases, ISBN 978-***********-6, eds. Frank S and Kostner G.

18. Lambe M, Wigertz A, Garmo H, Walldius G, Jungner I, Hammar N. Impaired glucose metabolism and diabetes and the risk of breast, endometrial and ovarian cancer. Cancer Causes Control 2011;22:1163-71.

19. VanHemelrijck M, Garmo H, Holmberg L et al. Prostate cancer risk in the swedish AMORIS study: the interplay among triglycerides, total cholesterol, and glucose. Cancer. 2011;17(10):2086 -95.

20. Van Hemelrijck M, Garmo H, Hammar N et al. Jungner I, Walldius G, Lambe M, et al. The interplay between lipid profiles, glucose, BMI and risk of kidney cancer in the Swedish AMORIS study. Int J Cancer. 2012 May 1;130(9):2118-28. PubMed PMID: 21630265. Epub 2011/06/02. eng.Vh kidney.

21. Wulaningsih W, Garmo H, Holmberg L et al. Serum Lipids and the Risk of Gastrointestinal Malignancies in the Swedish AMORIS Study. J Cancer Epidemiol. 2012;2012:792034. PubMed PMID: 22969802. Pubmed Central PMCID: 3437288. Epub 2012/09/13. eng.Wulan gi.

22. Melvin JC, Seth D, Holmberg L, et al. Lipid profiles and risk of breast and ovarian cancer in the Swedish AMORIS study. Cancer Epidemiol Biomarkers Prev. 2012 Aug;21(8):1381-1384. PubMed PMID: 22593241. Epub 2012/05/18. eng.

23. Seth D, Garmo H, Wigertz A et al. Lipid profiles and the risk of endometrial cancer in the Swedish AMORIS study. Int J Mol Epidemiol Genet. 2012;3(2):122-33. PubMed PMID: 22724049. Pubmed Central PMCID: 3376923. Epub 2012/06/23. eng.

24. Van Hemelrijck M, Garmo H, Binda E et al. Immunoglobulin E and cancer: a meta-analysis and a large Swedish cohort study. Cancer Causes Control. 2010; 21(10):1657-67.

25. Van Hemelrijck M, Jungner I, Walldius G et al. Risk of prostate cancer is not associated with levels of C-reactive protein and other commonly used markers of inflammation. Int J Cancer. 2010 Nov 15. PubMed PMID: 21080438. Epub 2010/11/17. Eng.

26. Van Hemelrijck M, Holmberg L, Garmo H, Hammar N et al. Association between levels of C-reactive protein and leukocytes and cancer: Three repeated measurements in the Swedish AMORIS study. Cancer Epidemiology Biomarkers and Prevention 2010; 20(2):428-37.

27. Wulaningsih W, Holmberg L, Garmo H, et al. Prediagnostic serum inflammatory markers in relation to breast cancer risk, severity at diagnosis and survival in breast cancer patients. Carcinogenesis. 2015 Oct;36(10):1121-28.

28. Wulaningsih W, Holmberg L, Garmo H, Malmstrom H, Lambe M, Hammar N, et al. Serum lactate dehydrogenase and survival following cancer diagnosis. British Journal of Cancer. 2015;1-8; DOI:10.1038/bjc.2015.361.

29. Van Hemelrijck M, Jassem W, Walldius G et al. Gamma-glutamyl transferase and risk of cancer in a cohort of 545,460 persons – the Swedish AMORIS study. Eur. J. Cancer 2011:47(13):2033-41.