Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians

Abstract Background The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear. Methods We used data from Biobank Japan (n = 70,657–128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients. Results Our PRSs aggregating 84–549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10− 103 < P < 1.3 × 10− 75) and 3-year lipid changes (1.4 × 10− 6 < P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (β ± SE = 0.052 ± 0.002), 11.7% in TG (β ± SE = 0.111 ± 0.006), 5.8% in HDL-C (β ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (β ± SE = 0.081 ± 0.004) per one standard deviation increase in the corresponding PRS. However, their predictive power was attenuated in T2D patients (0.183 < r < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032–0.057 in the general population (7.5 × 10− 3 < P < 0.0400) and 0.029–0.069 in T2D patients (2.1 × 10− 10 < P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (β ± SE = 0.011 ± 0.005, Ptrend = 0.0182). Independent of conventional risk factors, the quintile of PRSs for TC [OR (95% CI) = 1.07 (1.03–1.11)], TG [OR (95% CI) = 1.05 (1.01–1.09)], and LDL-C [OR (95% CI) = 1.05 (1.01–1.09)] were significantly associated with increased risk of CHD in T2D patients (4.8 × 10− 4 < P < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association. Conclusions The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.

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The Relationship between Cardiovascular Risk Scores and Several Markers of Subclinical Atherosclerosis in an Asymptomatic Population

Journal of Clinical Medicine ◽

10.3390/jcm10050955 ◽

2021 ◽

Vol 10 (5) ◽

pp. 955

Author(s):

Ovidiu Mitu ◽

Adrian Crisan ◽

Simon Redwood ◽

Ioan-Elian Cazacu-Davidescu ◽

Ivona Mitu ◽

...

Keyword(s):

Risk Score ◽

Subclinical Atherosclerosis ◽

Ankle Brachial Index ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Risk Scores ◽

Cvd Risk ◽

Cross Sectional ◽

Single Center Study ◽

Asymptomatic Individuals

Background: The current cardiovascular disease (CVD) primary prevention guidelines prioritize risk stratification by using clinical risk scores. However, subclinical atherosclerosis may rest long term undetected. This study aimed to evaluate multiple subclinical atherosclerosis parameters in relation to several CV risk scores in asymptomatic individuals. Methods: A cross-sectional, single-center study included 120 asymptomatic CVD subjects. Four CVD risk scores were computed: SCORE, Framingham, QRISK, and PROCAM. Subclinical atherosclerosis has been determined by carotid intima-media thickness (cIMT), pulse wave velocity (PWV), aortic and brachial augmentation indexes (AIXAo, respectively AIXbr), aortic systolic blood pressure (SBPao), and ankle-brachial index (ABI). Results: The mean age was 52.01 ± 10.73 years. For cIMT—SCORE was more sensitive; for PWV—Framingham score was more sensitive; for AIXbr—QRISK and PROCAM were more sensitive while for AIXao—QRISK presented better results. As for SBPao—SCORE presented more sensitive results. However, ABI did not correlate with any CVD risk score. Conclusions: All four CV risk scores are associated with markers of subclinical atherosclerosis in asymptomatic population, except for ABI, with specific particularities for each CVD risk score. Moreover, we propose specific cut-off values of CV risk scores that may indicate the need for subclinical atherosclerosis assessment.

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Carotid Plaques Correlates in Patients With Familial Hypercholesterolemia

Angiology ◽

10.1177/0003319715596281 ◽

2015 ◽

Vol 67 (5) ◽

pp. 471-477 ◽

Cited By ~ 9

Author(s):

Małgorzata Waluś-Miarka ◽

D. Czarnecka ◽

W. Wojciechowska ◽

M. Kloch-Badełek ◽

M. Kapusta ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Subclinical Atherosclerosis ◽

Density Lipoprotein ◽

High Sensitivity ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Apo B ◽

Carotid Plaques ◽

Premature Cardiovascular Disease ◽

Increased Risk

Patients with familial hypercholesterolemia (FH) are at increased risk of premature cardiovascular disease. We compared factors associated with the presence of carotid plaques and carotid intima–media thickness (cIMT), markers of subclinical atherosclerosis, in 241 patients with FH (98, 40.7% men; mean age 41 ± 18.4 years). Patients with FH having carotid plaques (36.5%) had mean age, apolipoprotein (apo) B, glucose, apoA1, systolic blood pressure (SBP) and diastolic BP, waist/hip ratio (WHR), and body mass index higher than patients without plaques. Logistic regression revealed that apoB (odds ratio [OR] per 1 unit change 1.03, P = .005), high-density lipoprotein cholesterol (HDL-C; OR per 1 standard deviation [SD] change 0.59, P = .015), and non-HDL-C (OR per 1SD change 1.53, P = .04) were significantly associated with the presence of plaques. The cIMT correlated with obesity parameters, BP, apoB, glucose, high-sensitivity C-reactive protein, creatinine, γ-glutamyl transpeptidase, and alanine transaminase ( P < .001). Regression analysis revealed that cIMT was significantly associated with apoB, SBP, and WHR. These results confirm the role of apoB-containing lipoproteins and low HDL-C with the presence of carotid plaques and apoB, BP, and WHR with cIMT.

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1145Obesity-related changes in metabolomic profiles in youth

International Journal of Epidemiology ◽

10.1093/ije/dyab168.416 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Toby Mansell ◽

Matthew Sabin ◽

Zoe McCallum ◽

Markus Juonala ◽

David Burgner ◽

...

Keyword(s):

Cardiovascular Disease ◽

Subclinical Atherosclerosis ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Childhood And Adolescence ◽

Metabolic Dysfunction ◽

Metabolomic Profile ◽

Early Effect ◽

Analogous Data ◽

The Relationship

Abstract Background Obesity during childhood and adolescence is linked to subclinical atherosclerosis, metabolic dysfunction and later cardiovascular disease. Adults with obesity have metabolomic profiles that predict cardiovascular disease and mortality. Analogous data from children with obesity are sparse. Here, we aimed to investigate i) the relationship between the severity of obesity (determined by the percentage above the 95th BMI-centile (%>95th BMI-centile)) and metabolomic profiles, ii) the effect of changes in the severity of obesity on the metabolomic profile and iii) the relationship between obesity-related metabolites and subclinical atherosclerosis outcomes. Methods Participants from the Childhood Overweight Biorepository of Australia (COBRA) cohort had %>95th BMI-centile and NMR metabolomic profile (Nightingale, Finland) from fasted blood analysed at two time-points (mean interval of 5.5 years). At the follow-up visit, subclinical atherosclerosis phenotypes (carotid elasticity, carotid intima-media thickness, and pulse-wave velocity) were assessed. Results There were 98 participants who attended both visit 1 (mean %>95th BMI-centile 134.6±19.0) and visit 2 (mean %>95th BMI-centile 130.7±26.2). Higher absolute, and increasing severity, of obesity between visits were associated with increased phenylalanine, tyrosine, GlycA (a marker of chronic inflammation), and pyruvate, in both sexes (estimated increases of 0.14-0.18 standard deviations per 10% BMI-centile at visit 2, and 0.15-0.25 per 10% increase in BMI-centile between visits). There was modest evidence for a relationship between lower alanine and higher carotid elasticity. Conclusions In children with obesity, the overall severity of obesity and changes in obesity severity were associated with a metabolomic pattern that in adults is predictive of cardiovascular disease. In children, these metabolites were not related subclinical atherosclerosis; these relationships may become manifest with increasing age. Key messages There is evidence for an early effect of severe obesity on metabolomic profiles in childhood and adolescence.

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Abstract P074: Restless Legs Syndrome and Carotid Intima-Media Thickness in Women

Circulation ◽

10.1161/circ.131.suppl_1.p074 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Karen Jacobo ◽

Adriana Monge ◽

Eduardo Ortiz-Panozo ◽

Elsa Yunes ◽

Andres Catzin-Khulmann ◽

...

Keyword(s):

Restless Legs Syndrome ◽

Subclinical Atherosclerosis ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Mean Difference ◽

Lower Limbs ◽

Cross Sectional ◽

Restless Legs ◽

Media Thickness ◽

Increased Risk

Introduction: Restless legs syndrome (RLS) is a common chronic disorder characterized by an irresistible need to move the lower limbs that is usually worse in the evening and is associated with sleep disturbances. RLS has been associated with hypertension and has been proposed as a marker for increased cardiovascular risk. Hypothesis: Individuals with RLS have an increased common carotid intima-media thickness (cIMT) relative to individuals without RLS. Methods: We evaluated cross-sectional relation of RLS and cIMT in 1,147 disease-free Mexican women of the Mexican Teachers’ Cohort. In 2011, participants responded to a follow-up questionnaire that included standardized questions addressing the four minimal diagnostic criteria of the International Restless Legs Study Group. Participants were asked: “Do you have unpleasant leg sensations (like crawling, loss of sensation or pain) combined with restlessness and an urge to move your legs?”, “Do these symptoms occur only at rest?”, “Does moving improve these symptoms?”, “Are these symptoms worse in the evening or at night compared with the morning?” Women who answered yes to all the four questions were defined as having RLS. Between 2012 and 2013, a subsample of participants were invited for a clinical visit where neurologists assessed cIMT with an ultrasound. cIMT measurements were found to be reproducible in a substudy in 52 participants (intra-class correlation=0.89). We defined subclinical atherosclerosis as a cIMT ≥0.8 mm or the presence of plaque. Results: Among women with a mean age of 48.2 (SD±4.3), the prevalence of RLS was 14.2% (cases, 163). The age-adjusted mean difference of cIMT comparing participants with RLS to those without RLS was 0.009mm (95%CI -0.004 to 0.023). After further adjustment for diabetes, hypercholesterolemia, migraine, oral contraceptive use, menopause, smoking, body mass index, physical activity and alcohol, the mean difference of cIMT comparing participants with and without RLS was not statistically different (0.007mm; 95%CI -0.007 to 0.021). The prevalence of subclinical atherosclerosis was 27% (n=44) in those with RLS and 21.9% (n=215) in those without RLS. The age-adjusted OR comparing women with RLS to those without RLS was 1.23 (95%CI 0.83-1.82). In the multivariable model the OR remained non-significant (1.16, 95%CI 0.77-1.74). Conclusions: In this cross-sectional study in middle-aged women, RLS was not associated to cIMT. Our results do not support the observation that individuals with RLS are at an increased risk for cardiovascular disease.

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Association of prehypertension and hyperhomocysteinemia with subclinical atherosclerosis in asymptomatic Chinese: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2017-019829 ◽

2018 ◽

Vol 8 (3) ◽

pp. e019829 ◽

Cited By ~ 7

Author(s):

Bo Liu ◽

Zhihao Chen ◽

Xiaoqi Dong ◽

Guangming Qin

Keyword(s):

Risk Factor ◽

Subclinical Atherosclerosis ◽

Multiple Logistic Regression Analysis ◽

Fasting Blood Glucose ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Control Group ◽

Cross Sectional ◽

Increased Risk ◽

Significant Difference

ObjectivesComorbid hypertension and hyperhomocysteinemia is an important risk factor for carotid atherosclerotic plaque formation. We put forward the hypothesis that the subjects with comorbid prehypertension and hyperhomocysteinemia also had an increased risk of subclinical atherosclerosis, using carotid intima–media thickness (CIMT) as the marker of the atherosclerotic process.MethodsA total of 4102 asymptomatic Chinese subjects aged 18–60 years were divided into four groups according to blood pressure (BP) and homocysteine (HCY) level: the control group without prehypertension or hyperhomocysteinemia, isolated prehypertension group, simple hyperhomocysteinemia group and prehypertension with hyperhomocysteinemia group. Serum lipids, fasting blood glucose (FBG), HCY and CIMT were measured.ResultsThere was significant difference in the positive rates of increased CIMT among four groups. Compared with the controls, the subjects in the other three groups had a higher risk of increased CIMT (isolated prehypertension group, OR 2.049, 95% CI 1.525 to 2.754; simple hyperhomocysteinemia group, OR 2.145, 95% CI 1.472 to 3.125; prehypertension and hyperhomocysteinemia group, OR 3.199, 95% CI 2.362 to 4.332). However, by multiple logistic regression analysis, only comorbid prehypertension and hyperhomocysteinemia was independently associated with increased CIMT (OR 1.485, 95% CI 1.047 to 2.108, P<0.05).ConclusionsComorbid prehypertension and hyperhomocysteinemia was an independent risk factor of subclinical atherosclerosis in asymptomatic Chinese, but isolated prehypertension or hyperhomocysteinemia was not. Therefore, combined intervention for prehypertension and hyperhomocysteinemia may contribute to decrease the incident of cardiovascular disease.

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Novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide

10.1101/451971 ◽

2018 ◽

Author(s):

Rona J. Strawbridge ◽

Joey Ward ◽

Amy Ferguson ◽

Nicholas Graham ◽

Richard J Shaw ◽

...

Keyword(s):

Psychiatric Disorders ◽

Risk Scores ◽

Worth Living ◽

Uk Biobank ◽

Chromosome 11 ◽

Polygenic Risk ◽

Completed Suicide ◽

Genome Wide ◽

Increased Risk ◽

Self Harm

Abstract:Background: Suicide is a major issue for global public health. ‘Suicidality’ describes a broad clinical spectrum of thoughts and behaviours, some of which are common in the general population.Methods: UK Biobank recruited ∼0·5 million middle age individuals from the UK, of whom 157,000 completed an assessment of suicidality. Mutually exclusive groups were assessed in an ordinal genome-wide association study of suicidality: ‘no suicidality’ controls (N=83,557); ‘thoughts that life was not worth living’ (N=21,063); ‘ever contemplated self-harm’ (N=13,038); ‘an act of deliberate self-harm in the past’ (N=2,498); and ‘a previous suicide attempt’ (N=2,666). Linkage of UK Biobank to death certification records identified a small sub-group of ‘completed suicide’ (N=137).Outcomes: We identified three novel genome-wide significant loci for suicidality (on Chromosomes 9, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0·81). Higher polygenic risk scores for suicidality were associated with increased risk of completed suicide relative to controls in an independent sub-group (N=137 vs N=5,330, OR 1·23, 95%CI 1·06 to 1·41, p=0.03). Rs598046-G (chromosome 11) demonstrated a similar effect size and direction (p=0·05) within a Danish suicidality study.Interpretation: These findings have significant implications for our understanding of genetic vulnerability to suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level.Funding: UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217).

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DAPSA, carotid plaque and cardiovascular events in psoriatic arthritis: a longitudinal study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-217595 ◽

2020 ◽

Vol 79 (10) ◽

pp. 1320-1326

Author(s):

Steven Ho Man Lam ◽

Isaac T Cheng ◽

Edmund K Li ◽

Priscilla Wong ◽

Jolie Lee ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Carotid Plaque ◽

Cohort Analysis ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Risk Scores ◽

Cvd Risk ◽

Increased Risk ◽

Cox Proportional Hazard Models ◽

Cv Disease

ObjectiveTo examine whether Disease Activity in Psoriatic Arthritis (DAPSA) reflecting the inflammatory component of psoriatic arthritis (PsA) can predict cardiovascular (CV) events independent of traditional CV risk factors and subclinical carotid atherosclerosis.MethodsA cohort analysis was performed in patients with PsA who had been followed since 2006. The outcome of interest was first CV event. Four different CV disease (CVD) risk scores and DAPSA were computed at baseline. The presence of carotid plaque (CP) and carotid intima-media thickness (CIMT) was also determined in a subgroup of patients using high-resolution ultrasound. The association between DAPSA, CVD risk scores, CP, CIMT and the occurrence of CV events was assessed using Cox proportional hazard models.Results189 patients with PsA (mean age: 48.9 years; male: 104 (55.0%)) were recruited. After a median follow-up of 9.9 years, 27 (14.3%) patients developed a CV event. Higher DAPSA was significantly associated with an increased risk of developing CV events (HR: 1.04, 95% CI (1.01 to 1.08), p=0.009). The association remained significant after adjusting for all CV risk scores in the multivariable models. In the subgroup analysis, 154 patients underwent carotid ultrasound assessment and 23 (14.9%) of them experienced a CV event. CP was associated with increased risk of developing CV events after adjusting for three CV risk scores and DAPSA, with HR ranging from 2.35 to 3.42.ConclusionHigher DAPSA and the presence of CP could independently predict CVD events in addition to traditional CV risk scores in patients with PsA.

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Biomarkers of subclinical atherosclerosis in patients with psoriasis

Scientific Reports ◽

10.1038/s41598-021-00999-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hannah Kaiser ◽

Xing Wang ◽

Amanda Kvist-Hansen ◽

Martin Krakauer ◽

Peter Michael Gørtz ◽

...

Keyword(s):

Large Scale ◽

Subclinical Atherosclerosis ◽

Vascular Inflammation ◽

Calcium Score ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Statin Treatment ◽

Positron Emission ◽

Increased Risk ◽

History Of

AbstractPsoriasis is linked with increased risk of cardiovascular disease (CVD) that is underestimated by traditional risk stratification. We conducted a large-scale plasma proteomic analysis by use of a proximity extension assay in 85 patients with a history of moderate-to-severe psoriasis with or without established atherosclerotic CVD. Differentially expressed proteins associated with CVD were correlated with subclinical atherosclerotic markers including vascular inflammation determined by 18F-fluorodeoxyglucose positron emission tomography/computed tomography, carotid intima-media thickness (CIMT), carotid artery plaques, and coronary artery calcium score (CCS) in the patients without CVD and statin treatment. We also examined the association between the neutrophil-to-lymphocyte ratio (NLR) and subclinical atherosclerosis. In unadjusted analyses, growth differentiation factor-15 (GDF-15) levels and NLR were increased, while tumor necrosis factor (TNF)-related activation-inducing ligand (TRANCE) and TNF-related apoptosis-induced ligand (TRAIL) levels were decreased in patients with established CVD compared to those without CVD. Among patients with psoriasis without CVD and statin treatment, GDF-15 levels were negatively associated with vascular inflammation in the ascending aorta and entire aorta, and positively associated with CIMT and CCS. NLR was positively associated with vascular inflammation in the carotid arteries. Our data suggest that circulating GDF-15 levels and NLR might serve as biomarkers of subclinical atherosclerosis in patients with psoriasis.

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Subclinical Atherosclerosis Markers of Carotid Intima-Media Thickness, Carotid Plaques, Carotid Stenosis, and Mortality in Community-Dwelling Adults

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17134745 ◽

2020 ◽

Vol 17 (13) ◽

pp. 4745

Author(s):

Chuan-Wei Yang ◽

Yuh-Cherng Guo ◽

Chia-Ing Li ◽

Chiu-Shong Liu ◽

Chih-Hsueh Lin ◽

...

Keyword(s):

Carotid Stenosis ◽

Carotid Plaque ◽

Subclinical Atherosclerosis ◽

Predictive Ability ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Community Dwelling ◽

Carotid Imt ◽

C Statistic ◽

Increased Risk

Carotid intima–media thickness (IMT), plaque, and stenosis are widely used as early surrogate markers of subclinical atherosclerosis and strong predictors of future deaths and cardiovascular events. Albuminuria is an indicator of generalized endothelial dysfunction that speeds up atherosclerosis. However, previous studies reporting these associations cannot rule out the confounding effect of albuminuria. We aimed to examine the independent and joint relationships between IMT markers and 10-year mortality in community-dwelling Taiwanese adults. This work was a community-based prospective cohort study consisting of 2956 adults aged at least 30 years recruited in 2007 and followed up through 2019. Cox proportional hazard regression models were used to examine associations of these subclinical atherosclerosis markers with mortality. During an average of 9.41 years of follow up, 242 deaths occurred. The mortality rate was 8.70 per 1000 person-years. Compared with those with carotid IMT less than 1.0 mm, persons with severely increased carotid IMT (≥2.0 mm) had an increased risk for death (hazard ratio (HR): 1.79; 95% confidence interval (CI): 1.07, 3.00). Compared with those without carotid plaque, persons with carotid plaque were more likely to have an increased risk for death (1.65; 1.21–2.32). Compared with those with carotid stenosis less than 25%, persons with carotid stenosis of 25–36% had a significant increased risk for death (1.57; 1.12–2.22). Considering these three IMT markers along with the traditional risk factors (c-statistic: 0.85) significantly increased their predictive ability of mortality compared with any individual variable’s predictive ability (all p-values < 0.001 for comparisons of c-statistic values). Carotid IMT measures, including IMT thickness, carotid plaque, and carotid stenosis were significant independent predictors of mortality. Our study supports evidence of blood pressure-related media thickening markers to assess future mortality risks in Chinese adults of general population.

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Pre-pregnancy overweight overtakes gestational diabetes as a risk factor for subsequent metabolic syndrome

Acta Endocrinologica ◽

10.1530/eje-13-0412 ◽

2013 ◽

Vol 169 (5) ◽

pp. 605-611 ◽

Cited By ~ 10

Author(s):

H Ijäs ◽

L Morin-Papunen ◽

A K Keränen ◽

R Bloigu ◽

A Ruokonen ◽

...

Keyword(s):

Metabolic Syndrome ◽

Gestational Diabetes ◽

Subclinical Atherosclerosis ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

University Hospital ◽

Control Group ◽

Oral Glucose ◽

Total Prevalence ◽

Increased Risk

ObjectiveGestational diabetes mellitus (GDM) is associated with an increased risk of subsequent diabetes and metabolic syndrome (MS). The independent significance of overweight, often associated with GDM, is controversial. This study was aimed to investigate the prevalence of MS and carotid intima-media thickness (CIMT) values in normal and overweight women with previous insulin-treated GDM and control without GDM 19 years after the index pregnancy.MethodsThe study group consisted of 61 women with prior GDM and 55 controls who gave birth in Oulu University Hospital between 1988 and 1993. These women were further divided into subgroups according to pre-pregnancy BMI (<25 or ≥25 kg/m2). In 2008–2010, anthropometrics and blood pressure were measured, blood samples were taken, and an oral glucose tolerance test was performed to investigate the components of MS. CIMT was measured by Doppler ultrasound.ResultsTotal prevalence of MS was 62% in the GDM group and 31% in the control group (P=0.001); it was highest (86%) in GDM women with pre-pregnancy overweight. CIMT was significantly thicker (0.67 vs 0.56 mm,P=0.007) and more often abnormal (71.7 vs 45.3%,P=0.004) in the GDM group compared with the controls. In logistic regression analysis, the strongest factor predicting MS in the whole study population was pre-pregnancy overweight.ConclusionsPre-pregnancy overweight was the strongest predictive factor for later MS, whereas GDM indicated increased risk of subsequent diabetes and subclinical atherosclerosis. The risk of MS was highest when both of these factors were present.

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