Aki S. Havulinna

Bio: Aki S. Havulinna is an academic researcher from National Institute for Health and Welfare. The author has contributed to research in topics: Population & Prospective cohort study. The author has an hindex of 24, co-authored 57 publications receiving 2134 citations. Previous affiliations of Aki S. Havulinna include University of Helsinki & National Institutes of Health.

Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors

Abstract: Circulating cytokines and growth factors are regulators of inflammation and have been implicated in autoimmune and metabolic diseases. In this genome-wide association study (GWAS) of up to 8,293 Finns we identified 27 genome-widely significant loci (p −9 ) for one or more cytokines. Fifteen of the associated variants had expression quantitative trait loci in whole blood. We provide genetic instruments to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases. We further link inflammatory markers with variants previously associated with autoimmune diseases such as Crohn disease, multiple sclerosis, and ulcerative colitis and hereby elucidate the molecular mechanisms underpinning these diseases and suggest potential drug targets.

Circulating Ceramides Predict Cardiovascular Outcomes in the Population-Based FINRISK 2002 Cohort.

Abstract: Objective— Ceramides are molecular lipids implicated in apoptosis, inflammation, obesity, and insulin resistance. An earlier study reported that ceramides were associated with fatal outcome among patients with coronary heart disease. Here, we examined whether ceramides are associated with major adverse cardiovascular events (MACEs) among apparently healthy individuals. Approach and Results— FINRISK 2002 is a population-based risk factor survey, which recruited men and women aged 25 to 74 years. The cohort was followed up until the end of 2014. We quantified 4 circulating ceramides, Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1), in 8101 serum samples by a targeted LC-MS/MS assay. Primary outcome of interest was incident MACE (n=813). Secondary analyses were performed for MACE death (n=116) without previous nonfatal MACE and for recurrent MACE (n=226) among survivors of a previous incident MACE. We used Cox proportional hazard models adjusted for the Framingham covariates to determine the association of ceramides with the outcomes. Of the ceramide species, Cer(d18:1/18:0) had the strongest association with incident MACE and the highest unadjusted hazard ratio of 1.31 (95% confidence interval, 1.21–1.41), which remained significant at 1.21 (95% confidence interval, 1.11–1.33) after Framingham risk factor adjustments. The hazard ratios were generally stronger for recurrent and fatal events than for first events. Clinical net reclassification improvement was 7.5% ( P =6.9×10−5) for Cer(d18:1/18:0). Conclusions— Distinct serum ceramides are associated with the risk of incident MACE in apparently healthy individuals. These results should encourage more detailed analyses of ceramides in cardiovascular pathobiology and suggest new biomarkers of MACE risk.

Genome-Wide Screen for Metabolic Syndrome Susceptibility Loci Reveals Strong Lipid Gene Contribution but No Evidence for Common Genetic Basis for Clustering of Metabolic Syndrome Traits

Abstract: Background—Genome-wide association (GWA) studies have identified several susceptibility loci for metabolic syndrome (MetS) component traits, but have had variable success in identifying susceptibil...

A metabolic view on menopause and ageing

Abstract: The ageing of the global population calls for a better understanding of age-related metabolic consequences. Here we report the effects of age, sex and menopause on serum metabolites in 26,065 individuals of Northern European ancestry. Age-specific metabolic fingerprints differ significantly by gender and, in females, a substantial atherogenic shift overlapping the time of menopausal transition is observed. In meta-analysis of 10,083 women, menopause status associates with amino acids glutamine, tyrosine and isoleucine, along with serum cholesterol measures and atherogenic lipoproteins. Among 3,204 women aged 40-55 years, menopause status associates additionally with glycine and total, monounsaturated, and omega-7 and -9 fatty acids. Our findings suggest that, in addition to lipid alterations, menopause may contribute to future metabolic and cardiovascular risk via influencing amino-acid concentrations, adding to the growing evidence of the importance of amino acids in metabolic disease progression. These observations shed light on the metabolic consequences of ageing, gender and menopause at the population level.

Twenty-five-year trends in myocardial infarction attack and mortality rates, and case-fatality, in six European populations

Abstract: Objective Due to the burden of coronary heart disease (CHD), the monitoring of CHD trends is required. This study sought to examine the acute myocardial infarction (AMI) trends in attack and mortality rates, and in 28-day case-fatality, in six European populations during 1985–2010. Methods Data consisted of 78 128 AMI events included in eight population-based registries from Finland (several populations), Italy (Brianza and Varese), Germany (Augsburg), France (Haute-Garonne), Spain (Girona) and Estonia (Tallinn). AMI event rates and case-fatality trends were analysed using the annual percentage change (APC) obtained by negative binomial and joinpoint regression. Results AMI attack and mortality rates decreased in most populations. Finland experienced the steepest decline in attack rates (APC=−4.4% (95% CI −5.1 to −2.9) in men; −4.0% (−5.1 to −2.8), in women). Total-hospital and inhospital case-fatality decreased in all populations except in Tallinn. The steepest decline in total case-fatality occurred in Spain (−3.8% (−5.3 to −2.4) in men; −5.1% (−6.9 to −3.3) in women). Prehospital case-fatality trends differed significantly by population and sex. The trends for all included populations showed a significant decline in AMI event rates and case-fatality, in both sexes and all age groups. However, in women aged 65–74 years, a significant increase in total case-fatality occurred in 2005–2010 (4.7% (0.7 to 8.8)). Conclusions AMI event rates and inhospital case-fatality declined in 1985–2010 in almost all populations analysed. Prehospital case-fatality declined only in certain population groups, showing differences by sex. These results highlight the need of specific strategies in AMI prevention for certain groups and populations.

Pattern Recognition and Machine Learning

Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (Version 2012)

Abstract: ABI : ankle–brachial index ACCORD : Action to Control Cardiovascular Risk in Diabetes ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation AGREE : Appraisal of Guidelines Research and Evaluation AHA : American Heart Association apoA1 : apolipoprotein A1 apoB : apolipoprotein B CABG : coronary artery bypass graft surgery CARDS : Collaborative AtoRvastatin Diabetes Study CCNAP : Council on Cardiovascular Nursing and Allied Professions CHARISMA : Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance CHD : coronary heart disease CKD : chronic kidney disease COMMIT : Clopidogrel and Metoprolol in Myocardial Infarction Trial CRP : C-reactive protein CURE : Clopidogrel in Unstable Angina to Prevent Recurrent Events CVD : cardiovascular disease DALYs : disability-adjusted life years DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Trial ED : erectile dysfunction eGFR : estimated glomerular filtration rate EHN : European Heart Network EPIC : European Prospective Investigation into Cancer and Nutrition EUROASPIRE : European Action on Secondary and Primary Prevention through Intervention to Reduce Events GFR : glomerular filtration rate GOSPEL : Global Secondary Prevention Strategies to Limit Event Recurrence After MI GRADE : Grading of Recommendations Assessment, Development and Evaluation HbA1c : glycated haemoglobin HDL : high-density lipoprotein HF-ACTION : Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing HOT : Hypertension Optimal Treatment Study HPS : Heart Protection Study HR : hazard ratio hsCRP : high-sensitivity C-reactive protein HYVET : Hypertension in the Very Elderly Trial ICD : International Classification of Diseases IMT : intima-media thickness INVEST : International Verapamil SR/Trandolapril JTF : Joint Task Force LDL : low-density lipoprotein Lp(a) : lipoprotein(a) LpPLA2 : lipoprotein-associated phospholipase 2 LVH : left ventricular hypertrophy MATCH : Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke MDRD : Modification of Diet in Renal Disease MET : metabolic equivalent MONICA : Multinational MONItoring of trends and determinants in CArdiovascular disease NICE : National Institute of Health and Clinical Excellence NRT : nicotine replacement therapy NSTEMI : non-ST elevation myocardial infarction ONTARGET : Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial OSA : obstructive sleep apnoea PAD : peripheral artery disease PCI : percutaneous coronary intervention PROactive : Prospective Pioglitazone Clinical Trial in Macrovascular Events PWV : pulse wave velocity QOF : Quality and Outcomes Framework RCT : randomized clinical trial RR : relative risk SBP : systolic blood pressure SCORE : Systematic Coronary Risk Evaluation Project SEARCH : Study of the Effectiveness of Additional Reductions in Cholesterol and SHEP : Systolic Hypertension in the Elderly Program STEMI : ST-elevation myocardial infarction SU.FOL.OM3 : SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids Syst-Eur : Systolic Hypertension in Europe TNT : Treating to New Targets UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use VITATOPS : VITAmins TO Prevent Stroke VLDL : very low-density lipoprotein WHO : World Health Organization ### 1.1 Introduction Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur. It remains the major cause of premature death in Europe, even though CVD mortality has …

2016 European Guidelines on cardiovascular disease prevention in clinical practice

Abstract: ABI : ankle–brachial (blood pressure) index ABPM : ambulatory blood pressure monitoring ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE-I : angiotensin-converting enzyme inhibitor ACS : acute coronary syndromes ADVANCE : Action in Diabetes and Vascular disease: PreterAx

2016 European Guidelines on cardiovascular disease prevention in clinical practice

Abstract: Authors/Task Force Members: Massimo F. Piepoli* (Chairperson) (Italy), Arno W. Hoes* (Co-Chairperson) (The Netherlands), Stefan Agewall (Norway)1, Christian Albus (Germany)9, Carlos Brotons (Spain)10, Alberico L. Catapano (Italy)3, Marie-Therese Cooney (Ireland)1, Ugo Corrà (Italy)1, Bernard Cosyns (Belgium)1, Christi Deaton (UK)1, Ian Graham (Ireland)1, Michael Stephen Hall (UK)7, F. D. Richard Hobbs (UK)10, Maja-Lisa Løchen (Norway)1, Herbert Löllgen (Germany)8, Pedro Marques-Vidal (Switzerland)1, Joep Perk (Sweden)1, Eva Prescott (Denmark)1, Josep Redon (Spain)5, Dimitrios J. Richter (Greece)1, Naveed Sattar (UK)2, Yvo Smulders (The Netherlands)1, Monica Tiberi (Italy)1, H. Bart van der Worp (The Netherlands)6, Ineke van Dis (The Netherlands)4, W. M. Monique Verschuren (The Netherlands)1