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6. Lipid levels in midlife and risk of atrial fibrillation over 3 decades-Experience from the Swedish AMORIS cohort: A cohort study

Author

Ding, Mozhu, Wennberg, Alexandra, Gigante, Bruna, Walldius, Göran, Hammar, Niklas, and Modig, Karin

Subjects
Atrial fibrillation -- Risk factors -- Demographic aspects, Middle aged persons -- Health aspects, Blood lipids -- Measurement -- Health aspects, Biological sciences
Abstract

Background The role of cholesterol levels in the development of atrial fibrillation (AF) is still controversial. In addition, whether and to what extent apolipoproteins are associated with the risk of AF is rarely studied. In this study, we aimed to investigate the association between blood lipid levels in midlife and subsequent risk of new-onset AF. Methods and findings This population-based study included 65,136 individuals aged 45 to 60 years without overt cardiovascular diseases (CVDs) from the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort. Lipids were measured in 1985 to 1996, and individuals were followed until December 31, 2019 for incident AF (i.e., study outcome). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression, adjusting for age, sex, and socioeconomic status. Over a mean follow-up of 24.2 years (standard deviation 7.5, range 0.2 to 35.9), 13,871 (21.3%) incident AF cases occurred. Higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were statistically significantly associated with a lower risk of AF during the first 5 years of follow-up (HR = 0.61, 95% CI: 0.41 to 0.99, p = 0.013; HR = 0.64, 95% CI: 0.45 to 0.92, p = 0.016), but not thereafter (HR ranging from 0.94 [95% CI: 0.89 to 1.00, p = 0.038] to 0.96 [95% CI: 0.77 to 1.19, p > 0.05]). Lower levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) and higher triglycerides (TG)/HDL-C ratio were statistically significantly associated with a higher risk of AF during the entire follow-up (HR ranging from 1.13 [95% CI: 1.07 to 1.19, p < 0.001] to 1.53 [95% CI: 1.12 to 2.00, p = 0.007]). Apolipoprotein B (ApoB)/ApoA-I ratio was not associated with AF risk. The observed associations were similar among those who developed incident heart failure (HF)/coronary heart disease (CHD) and those who did not. The main limitations of this study include lack of adjustments for lifestyle factors and high blood pressure leading to potential residual confounding. Conclusions High TC and LDL-C in midlife was associated with a lower risk of AF, but this association was present only within 5 years from lipid measurement and not thereafter. On the contrary, low HDL-C and ApoA-I and high TG/HDL-C ratio were associated with an increased risk of AF over almost 35 years of follow-up. ApoB/ApoA-I ratio was not associated with AF risk., Author(s): Mozhu Ding 1,*, Alexandra Wennberg 1, Bruna Gigante 2, Göran Walldius 1, Niklas Hammar 1, Karin Modig 1 Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia in [...]

Published
2022
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8. Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study

Author

Walldius, Göran, de Faire, Ulf, Alfredsson, Lars, Leander, Karin, Westerholm, Peter, Malmström, Håkan, Ivert, Torbjörn, and Hammar, Niklas

Subjects
Apolipoproteins -- Health aspects -- Measurement, Cardiovascular diseases -- Risk factors -- Patient outcomes, Biological sciences
Abstract

Background Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop. Methods and findings In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25-84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan-Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case-control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study. Conclusions An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines., Author(s): Göran Walldius 1,*, Ulf de Faire 1, Lars Alfredsson 1, Karin Leander 1, Peter Westerholm 2, Håkan Malmström 1,3, Torbjörn Ivert 4,5, Niklas Hammar 1,* Introduction Dyslipidaemia is a [...]

Published
2021
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19. Improved prediction of 10‐year risk of severe liver disease in the general population using commonly available biomarkers.

Author

Hagström, Hannes, Yan, Jacinth, Talbäck, Mats, Andreasson, Anna, Walldius, Göran, Bottai, Matteo, and Hammar, Niklas

Subjects
LIVER diseases, BIOMARKERS, PERIODIC health examinations, PREDICTION models, FORECASTING
Abstract

Summary: Background: Estimating the risk for cirrhosis in the general population is complex. Existing prediction tools are in general unsatisfactory. Aims: To explore if using commonly available biomarkers can improve the commonly used FIB‐4 score in the identification of subgroups at risk of cirrhosis. Methods: We used laboratory and clinical data on 126,925 individuals aged 35–79 years in Stockholm, Sweden, undergoing health examinations from 1985 to 1996. We used Swedish nationwide registries to ascertain 10‐year cumulative incidence of severe liver disease, a composite of diagnoses corresponding to cirrhosis and its complications. We considered combinations of biomarkers associated with severe liver disease to identify subgroups with different risk profiles. Results: During an average follow‐up of 9.3 years, we ascertained 630 incident cases of severe liver disease (0.5%). Age, the FIB‐4 score, diabetes or impaired glucose and gamma‐glutamyl transferase (gGT) were the most relevant characteristics for classifying risk profiles. Using these factors, we identified 24 groups with a cumulative incidence of severe liver disease at 10 years ranging from 0.2% (age 35–65, low FIB‐4, no diabetes or impaired glucose and normal gGT) to 32.1% (age 35–65, high FIB‐4, diabetes or impaired glucose and high gGT). Conclusions: Identification of subjects at increased risk of severe liver disease in the general population using the FIB‐4 score can be substantially improved by adding age and specific biomarkers commonly available in the primary care setting. These parameters should be considered for inclusion in the development of future risk prediction models. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis

Author

Wormser, David, Angelantonio, Emanuele Di, Kaptoge, Stephen, Wood, Angela M, Gao, Pei, Sun, Qi, Walldius, Göran, Selmer, Randi, Verschuren, WM Monique, Bueno-de-Mesquita, H Bas, Engström, Gunnar, Ridker, Paul M, Njølstad, Inger, Iso, Hiroyasu, Holme, Ingar, Giampaoli, Simona, Tunstall-Pedoe, Hugh, Gaziano, J Michael, Brunner, Eric, Kee, Frank, Tosetto, Alberto, Meisinger, Christa, Brenner, Hermann, Ducimetiere, Pierre, Whincup, Peter H, Tipping, Robert W, Ford, Ian, Cremer, Peter, Hofman, Albert, Wilhelmsen, Lars, Clarke, Robert, Boer, Ian H de, Jukema, J Wouter, Ibañez, Alejandro Marín, Lawlor, Debbie A, DʼAgostino, Ralph B, Rodriguez, Beatriz, Casiglia, Edoardo, Stehouwer, Coen DA, Simons, Leon A, Nietert, Paul J, Barrett-Connor, Elizabeth, Panagiotakos, Demosthenes B, Björkelund, Cecilia, Strandberg, Timo E, Wassertheil-Smoller, Sylvia, Blazer, Dan G, Meade, Tom W, Welin, Lennart, Svärdsudd, Kurt, Woodward, Mark, Nissinen, Aulikki, Kromhout, Daan, Jørgensen, Torben, Tilvis, Reijo S, Guralnik, Jack M, Rosengren, Annika, Taylor, James O, Kiechl, Stefan, Dagenais, Gilles R, Gerry, F, Fowkes, R, Wallace, Robert B, Khaw, Kay-Tee, Shaffer, Jonathan A, Visser, Marjolein, Kauhanen, Jussi, Salonen, Jukka T, Gallacher, John, Ben-Shlomo, Yoav, Kitamura, Akihiko, Sundström, Johan, Wennberg, Patrik, Kiyohara, Yutaka, Daimon, Makoto, de la Cámara, Agustin Gómez, Cooper, Jackie A, Onat, Altan, Devereux, Richard, Mukamal, Kenneth J, Dankner, Rachel, Knuiman, Matthew W, Crespo, Carlos J, Gansevoort, Ron T, Goldbourt, Uri, Nordestgaard, Børge G, Shaw, Jonathan E, Mussolino, Michael, Nakagawa, Hidaeki, Fletcher, Astrid, Kuller, Lewis H, Gillum, Richard F, Gudnason, Vilmundur, Assmann, Gerd, Wald, Nicholas, Jousilahti, Pekka R, Greenland, Philip, Trevisan, Maurizio, Ulmer, Hanno, Butterworth, Adam S, Folsom, Aaron R, Davey-Smith, George, Hu, Frank B, Danesh, John, Tipping, Robert W, Ford, Charles E, Simpson, Lara M, Walldius, Göran, Jungner, Ingmar, Folsom, Aaron R, Demerath, Ellen W, Franceschini, Nora, Lutsey, Pamela L, Panagiotakos, Demosthenes B, Pitsavos, Christos, Chrysohoou, Christina, Stefanadis, Christodoulos, Shaw, Jonathan E, Atkins, Robert, Zimmet, Paul Z, Barr, Elizabeth LM, Knuiman, Matthew W, Whincup, Peter H, Wannamethee, S Goya, Morris, Richard W, Willeit, Johann, Kiechl, Stefan, Weger, Siegfried, Oberhollenzer, Friedrich, Wald, Nicholas, Ebrahim, Shah, Lawlor, Debbie A, Gallacher, John, Ben-Shlomo, Yoav, Yarnell, John WG, Casiglia, Edoardo, Tikhonoff, Valérie, Greenland, Philip, Shay, Christina M, Garside, Daniel B, Nietert, Paul J, Sutherland, Susan E, Bachman, David L, Keil, Julian E, de Boer, Ian H, Kizer, Jorge R, Psaty, Bruce M, Mukamal, Kenneth J, Nordestgaard, Børge G, Tybjærg-Hansen, Anne, Jensen, Gorm B, Schnohr, Peter, Giampaoli, Simona, Palmieri, Luigi, Panico, Salvatore, Pilotto, Lorenza, Vanuzzo, Diego, de la Cámara, Agustin Gómez, Simons, Leon A, Simons, Judith, McCallum, John, Friedlander, Yechiel, Gerry, F, Fowkes, R, Price, Jackie F, Lee, Amanda J, Taylor, James O, Guralnik, Jack M, Phillips, Caroline L, Wallace, Robert B, Kohout, Frank J, Cornoni-Huntley, Joan C, Guralnik, Jack M, Blazer, Dan G, Guralnik, Jack M, Phillips, Caroline L, Phillips, Caroline L, Guralnik, Jack M, Khaw, Kay-Tee, Wareham, Nicholas J, Brenner, Hermann, Schöttker, Ben, Müller, Heiko, Rothenbacher, Dietrich, Wennberg, Patrik, Jansson, Jan-Håkan, Nissinen, Aulikki, Donfrancesco, Chiara, Giampaoli, Simona, Woodward, Mark, Vartiainen, Erkki, Jousilahti, Pekka R, Harald, Kennet, Salomaa, Veikko, DʼAgostino, Ralph B, Vasan, Ramachandran S, Fox, Caroline S, Pencina, Michael J, Daimon, Makoto, Oizumi, Toshihide, Kayama, Takamasa, Kato, Takeo, Bladbjerg, Else-Marie, Jørgensen, Torben, Møller, Lars, Jespersen, Jørgen, Dankner, Rachel, Chetrit, Angela, Lubin, Flora, Svärdsudd, Kurt, Eriksson, Henry, Welin, Lennart, Lappas, Georgios, Rosengren, Annika, Lappas, Georgios, Welin, Lennart, Svärdsudd, Kurt, Eriksson, Henry, Lappas, Georgios, Bengtsson, Calle, Lissner, Lauren, Björkelund, Cecilia, Cremer, Peter, Nagel, Dorothea, Strandberg, Timo E, Salomaa, Veikko, Tilvis, Reijo S, Miettinen, Tatu A, Tilvis, Reijo S, Strandberg, Timo E, Kiyohara, Yutaka, Arima, Hisatomi, Doi, Yasufumi, Ninomiya, Toshiharu, Rodriguez, Beatriz, Dekker, Jacqueline M, Nijpels, Giel, Stehouwer, Coen DA, Hu, Frank B, Sun, Qi, Rimm, Eric B, Willett, Walter C, Iso, Hiroyasu, Kitamura, Akihiko, Yamagishi, Kazumasa, Noda, Hiroyuki, Goldbourt, Uri, Vartiainen, Erkki, Jousilahti, Pekka R, Harald, Kennet, Salomaa, Veikko, Kauhanen, Jussi, Salonen, Jukka T, Kurl, Sudhir, Tuomainen, Tomi-Pekka, Poppelaars, Jan L, Deeg, Dorly JH, Visser, Marjolein, Meade, Tom W, De Stavola, Bianca Lucia, Hedblad, Bo, Nilsson, Peter, Engström, Gunnar, Verschuren, WM Monique, Blokstra, Anneke, de Boer, Ian H, Shea, Steven J, Meisinger, Christa, Thorand, Barbara, Koenig, Wolfgang, Döring, Angela, Verschuren, WM Monique, Blokstra, Anneke, Bueno-de-Mesquita, H Bas, Wilhelmsen, Lars, Rosengren, Annika, Lappas, Georgios, Fletcher, Astrid, Nitsch, Dorothea, Kuller, Lewis H, Grandits, Greg, Tverdal, Aage, Selmer, Randi, Nystad, Wenche, Mussolino, Michael, Gillum, Richard F, Hu, Frank B, Sun, Qi, Manson, JoAnn E, Rimm, Eric B, Hankinson, Susan E, Meade, Tom W, De Stavola, Bianca Lucia, Cooper, Jackie A, Bauer, Kenneth A, Davidson, Karina W, Kirkland, Susan, Shaffer, Jonathan A, Shimbo, Daichi, Kitamura, Akihiko, Iso, Hiroyasu, Sato, Shinichi, Holme, Ingar, Selmer, Randi, Tverdal, Aage, Nystad, Wenche, Nakagawa, Hidaeki, Miura, Katsuyuki, Sakurai, Masaru, Ducimetiere, Pierre, Jouven, Xavier, Bakker, Stephan JL, Gansevoort, Ron T, van der Harst, Pim, Hillege, Hans L, Crespo, Carlos J, Garcia-Palmieri, Mario R, Kee, Frank, Amouyel, Philippe, Arveiler, Dominique, Ferrières, Jean, Schulte, Helmut, Assmann, Gerd, Jukema, J Wouter, de Craen, Anton JM, Sattar, Naveed, Stott, David J, Cantin, Bernard, Lamarche, Benoît, Després, Jean-Pierre, Dagenais, Gilles R, Barrett-Connor, Elizabeth, Bergstrom, Jaclyn, Bettencourt, Richele R, Buisson, Catherine, Gudnason, Vilmundur, Aspelund, Thor, Sigurdsson, Gunnar, Thorsson, Bolli, Trevisan, Maurizio, Hofman, Albert, Ikram, M Arfan, Tiemeier, Henning, Witteman, Jacqueline CM, Tunstall-Pedoe, Hugh, Tavendale, Roger, Lowe, Gordon DO, Woodward, Mark, Devereux, Richard, Yeh, Jeun-Liang, Ali, Tauqeer, Calhoun, Darren, Ben-Shlomo, Yoav, Davey-Smith, George, Onat, Altan, Can, Günay, Nakagawa, Hidaeki, Sakurai, Masaru, Nakamura, Koshi, Morikawa, Yuko, Njølstad, Inger, Mathiesen, Ellisiv B, Løchen, Maja-Lisa, Wilsgaard, Tom, Sundström, Johan, Ingelsson, Erik, Michaëlsson, Karl, Cederholm, Tommy, Gaziano, J Michael, Buring, Julie, Ridker, Paul M, Gaziano, J Michael, Ridker, Paul M, Ulmer, Hanno, Diem, Günter, Concin, Hans, Rodeghiero, Francesco, Tosetto, Alberto, Wassertheil-Smoller, Sylvia, Manson, JoAnn E, Marmot, Michael, Clarke, Robert, Fletcher, Astrid, Brunner, Eric, Shipley, Martin, Kivimaki, Mika, Ridker, Paul M, Buring, Julie, Ford, Ian, Robertson, Michele, Ibañez, Alejandro Marín, Feskens, Edith, Geleijnse, Johanna M, Kromhout, Daan, Walker, Matthew, Watson, Sarah, Alexander, Myriam, Butterworth, Adam S, Angelantonio, Emanuele Di, Franco, Oscar H, Gao, Pei, Gobin, Reeta, Haycock, Philip, Kaptoge, Stephen, Seshasai, Sreenivasa R Kondapally, Lewington, Sarah, Pennells, Lisa, Rapsomaniki, Eleni, Sarwar, Nadeem, Thompson, Alexander, Thompson, Simon G, Walker, Matthew, Watson, Sarah, White, Ian R, Wood, Angela M, Wormser, David, Zhao, Xiaohui, and Danesh, John

Published
2012
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29. Alterations in Biomarkers Related to Glycemia, Lipid Metabolism, and Inflammation up to 20 Years Before Diagnosis of Type 1 Diabetes in Adults: Findings From the AMORIS Cohort.

Author

Herzog, Katharina, Andersson, Tomas, Grill, Valdemar, Hammar, Niklas, Malmströom, Håkan, Talbäack, Mats, Walldius, Göoran, Carlsson, Sofia, Malmström, Håkan, Talbäck, Mats, and Walldius, Göran

Subjects
TYPE 1 diabetes, HYPERGLYCEMIA, LIPID metabolism, ALKALINE phosphatase, ADULTS, BIOMARKERS
Abstract

Objective: Type 1 diabetes is described to have an acute onset, but autoantibodies can appear several years preceding diagnosis. This suggests a long preclinical phase, which may also include metabolic parameters. Here we assessed whether elevations in glycemic, lipid, and other metabolic biomarkers were associated with future type 1 diabetes risk in adults.Research Design and Methods: We studied 591,239 individuals from the Swedish AMORIS cohort followed from 1985-1996 to 2012. Through linkage to national patient, diabetes, and prescription registers, we identified incident type 1 diabetes. Using Cox regression models, we estimated hazard ratios for biomarkers at baseline and incident type 1 diabetes. We additionally assessed trajectories of biomarkers during the 25 years before type 1 diabetes diagnosis in a nested case-control design.Results: We identified 1,122 type 1 diabetes cases during follow-up (average age of patient at diagnosis: 53.3 years). The biomarkers glucose, fructosamine, triglycerides, the ratio of apolipoprotein (apo)B to apoA-I, uric acid, alkaline phosphatase, and BMI were positively associated with type 1 diabetes risk. Higher apoA-I was associated with lower type 1 diabetes incidence. Already 15 years before diagnosis, type 1 diabetes cases had higher mean glucose, fructosamine, triglycerides, and uric acid levels compared with control subjects.Conclusions: Alterations in biomarker levels related to glycemia, lipid metabolism, and inflammation are associated with clinically diagnosed type 1 diabetes risk, and these may be elevated many years preceding diagnosis. [ABSTRACT FROM AUTHOR]

Published
2022
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34. A Swedish primary healthcare prevention programme focusing on promotion of physical activity and a healthy lifestyle reduced cardiovascular events and mortality: 22-year follow-up of 5761 study participants and a reference group

Author

Journath, Gunilla, primary, Hammar, Niklas, additional, Vikström, Max, additional, Linnersjö, Anette, additional, Walldius, Göran, additional, Krakau, Ingvar, additional, Lindgren, Peter, additional, de Faire, Ulf, additional, and Hellenius, Mai-Lis, additional

Published
2020
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40. Circulating uric acid levels and subsequent development of cancer in 493,281 individuals: findings from the AMORIS Study

Author

Yiu, Andrew, Van Hemelrijck, Mieke, Garmo, Hans, Holmberg, Lars, Malmström, Håkan, Lambe, Mats, Hammar, Niklas, Walldius, Göran, Jungner, Ingmar, and Wulaningsih, Wahyu

Subjects
Male, Sweden, Cancer och onkologi, Incidence, Uric Acid, Social Class, Cancer and Oncology, Neoplasms, Population Surveillance, cancer, Humans, Female, Prospective study, Uric acid, Cancer, Research Paper, prospective study, Follow-Up Studies, Proportional Hazards Models
Abstract

Objectives: Serum uric acid has been suggested to be associated with cancer risk. We aimed to study the association between serum uric acid and cancer incidence in a large Swedish cohort. Results: A positive association was found between uric acid levels and overall cancer risk, and results were similar with adjustment for glucose, triglycerides and BMI. Hazard ratio (HR) for overall cancer for the 4th quartile of uric acid compared to the 1st was 1.08 (95% CI: 1.05-1.11) in men and 1.12 (1.09 - 1.16) in women. Site-specific analysis showed a positive association between uric acid and risk of colorectal, hepatobiliary, kidney, nonmelanoma skin, and other cancers in men and of head and neck and other cancers in women. An inverse association was observed for pulmonary and central nervous system (CNS) cancers in men and breast, lymphatic and haematological, and CNS malignancies in women. Materials and Methods: We included 493,281 persons aged 20 years and older who had a measurement of serum uric acid and were cancer-free at baseline in the AMORIS study. Multivariable Cox proportional hazards regression was used to investigate sex-specific quartiles of serum uric acid in relation to cancer risk in men and women. Analysis was further adjusted for serum glucose, triglycerides and, where available, BMI. Site-specific analysis was performed for major cancers. Conclusions: Altered uric acid levels were associated with risk of overall and some specific cancers, further indicating the potential role of uric acid metabolism in carcinogenesis.

Published
2017

49. Serum glucose, triglycerides, and cholesterol in relation to prostate cancer death in the Swedish AMORIS study

Author

Arthur, Rhonda, primary, Møller, Henrik, additional, Garmo, Hans, additional, Häggström, Christel, additional, Holmberg, Lars, additional, Stattin, Pär, additional, Malmström, Håkan, additional, Lambe, Mats, additional, Hammar, Niklas, additional, Walldius, Göran, additional, Robinson, David, additional, Jungner, Ingmar, additional, and Van Hemelrijck, Mieke, additional

Published
2018
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