| 1. |
- Arnold, Natalie, et al.
(författare)
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C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease : the BiomarCaRE project
- 2024
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 45:12, s. 1043-1054
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population.Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L).Results: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024).Conclusions: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.
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| 2. |
- Arnold, Natalie, et al.
(författare)
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Impact of lipoprotein(a) level on low-density lipoprotein cholesterol– or apolipoprotein B–related risk of coronary heart disease
- 2024
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 84:2, s. 165-177
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities.Objectives: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events.Methods: Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as “LDL-C—Lp(a)-C,” where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile).Results: Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49).Conclusions: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.
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| 3. |
- Ferrario, Marco M., et al.
(författare)
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Determinants of social inequalities in stroke incidence across Europe : a collaborative analysis of 126 635 individuals from 48 cohort studies
- 2017
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ PUBLISHING GROUP. - 0143-005X .- 1470-2738. ; 71:12, s. 1210-1216
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Tidskriftsartikel (refereegranskat)abstract
- Background: Knowledge on the origins of the social gradient in stroke incidence in different populations is limited. This study aims to estimate the burden of educational class inequalities in stroke incidence and to assess the contribution of risk factors in determining these inequalities across Europe.Materials and methods: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) Study comprises 48 cohorts recruited mostly in the 1980s and 1990s in four European regions using standardised procedures for baseline risk factor assessment and fatal and non-fatal stroke ascertainment and adjudication during follow-up. Among the 126 635 middle-aged participants, initially free of cardiovascular diseases, generating 3788 first stroke events during a median follow-up of 10 years, we estimated differences in stroke rates and HRs for the least versus the most educated individuals.Results: Compared with their most educated counterparts, the overall age-adjusted excess hazard for stroke was 1.54 (95% CI 1.25 to 1.91) and 1.41 (95% CI 1.16 to 1.71) in least educated men and women, respectively, with little heterogeneity across populations. Educational class inequalities accounted for 86–413 and 78–156 additional stroke events per 100 000 person-years in the least compared with most educated men and women, respectively. The additional events were equivalent to 47%–130% and 40%–89% of the average incidence rates. Inequalities in risk factors accounted for 45%–70% of the social gap in incidence in the Nordic countries, the UK and Lithuania-Kaunas (men), but for no more than 17% in Central and South Europe. The major contributors were cigarette smoking, alcohol intake and body mass index.Conclusions: Social inequalities in stroke incidence contribute substantially to the disease rates in Europe. Healthier lifestyles in the most disadvantaged individuals should have a prominent impact in reducing both inequalities and the stroke burden.
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| 4. |
- Hicks, Blánaid, et al.
(författare)
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Roles of allostatic load, lifestyle and clinical risk factors in mediating the association between education and coronary heart disease risk in Europe
- 2021
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ Publishing Group Ltd. - 0143-005X .- 1470-2738. ; 75:12, s. 1147-1154
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have shown that differential exposure to lifestyle factors may mediate the association between education and coronary heart diseases (CHD). However, few studies have examined the potential roles of allostatic load (AL) or differential susceptibility.Methods: 25 310 men and 26 018 women aged 35–74 and CHD free at baseline were identified from 21 European cohorts and followed for a median of 10 years, to investigate the mediating role of AL, as well as of smoking, alcohol use and body mass index (BMI), on educational differences in CHD incidence, applying marginal structural models and three-way decomposition.Results: AL is a mediator of the association between educational status and CHD incidence, with the highest proportion mediated observed among women and largely attributable to differential exposure, (28% (95% CI 19% to 44%)), with 8% (95% CI 0% to 16%) attributable to differential susceptibility. The mediating effects of smoking, alcohol and BMI, compared with AL, were relatively small for both men and women.Conclusion: Overall, the educational inequalities in CHD incidence were partially mediated through differential exposure to AL. By contrast, the mediation of the educational gradient in CHD by investigated lifestyle risk factors was limited. As differential susceptibility in men was found to have a predominant role in the accumulation of AL in low educational classes, the investigation of AL-related risk factors is warranted.
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| 5. |
- Jülicher, Paul, et al.
(författare)
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Cost-effectiveness of applying high-sensitivity troponin I to a score for cardiovascular risk prediction in asymptomatic population
- 2024
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Risk stratification scores such as the European Systematic COronary Risk Evaluation (SCORE) are used to guide individuals on cardiovascular disease (CVD) prevention. Adding high-sensitivity troponin I (hsTnI) to such risk scores has the potential to improve accuracy of CVD prediction. We investigated how applying hsTnI in addition to SCORE may impact management, outcome, and cost-effectiveness.Methods: Characteristics of 72,190 apparently healthy individuals from the Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project were included into a discrete-event simulation comparing two strategies for assessing CVD risk. The standard strategy reflecting current practice employed SCORE (SCORE); the alternative strategy involved adding hsTnI information for further stratifying SCORE risk categories (S-SCORE). Individuals were followed over ten years from baseline examination to CVD event, death or end of follow-up. The model tracked the occurrence of events and calculated direct costs of screening, prevention, and treatment from a European health system perspective. Cost-effectiveness was expressed as incremental cost-effectiveness ratio (ICER) in € per quality-adjusted life year (QALYs) gained during 10 years of follow-up. Outputs were validated against observed rates, and results were tested in deterministic and probabilistic sensitivity analyses.Results: S-SCORE yielded a change in management for 10.0% of individuals, and a reduction in CVD events (4.85% vs. 5.38%, p<0.001) and mortality (6.80% vs. 7.04%, p<0.001). S-SCORE led to 23 (95%CI: 20–26) additional event-free years and 7 (95%CI: 5–9) additional QALYs per 1,000 subjects screened, and resulted in a relative risk reduction for CVD of 9.9% (95%CI: 7.3–13.5%) with a number needed to screen to prevent one event of 183 (95%CI: 172 to 203). S-SCORE increased costs per subject by 187€ (95%CI: 177 € to 196 €), leading to an ICER of 27,440€/QALY gained. Sensitivity analysis was performed with eligibility for treatment being the most sensitive.Conclusion: Adding a person’s hsTnI value to SCORE can impact clinical decision making and eventually improves QALYs and is cost-effective compared to CVD prevention strategies using SCORE alone. Stratifying SCORE risk classes for hsTnI would likely offer cost-effective alternatives, particularly when targeting higher risk groups.
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| 6. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 7. |
- Rosberg, Victoria, et al.
(författare)
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Simple cardiovascular risk stratification by replacing total serum cholesterol with anthropometric measures : The MORGAM prospective cohort project
- 2022
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Ingår i: Preventive Medicine Reports. - : Elsevier. - 2211-3355. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- To assess whether anthropometric measures (body mass index [BMI], waist-hip ratio [WHR], and estimated fat mass [EFM]) are independently associated with major adverse cardiovascular events (MACE), and to assess their added prognostic value compared with serum total-cholesterol. The study population comprised 109,509 individuals (53% men) from the MORGAM-Project, aged 19–97 years, without established cardiovascular disease, and not on antihypertensive treatment. While BMI was reported in all, WHR and EFM were reported in ∼52,000 participants. Prognostic importance of anthropometric measurements and total-cholesterol was evaluated using adjusted Cox proportional-hazards regression, logistic regression, area under the receiver-operating-characteristic curve (AUCROC), and net reclassification improvement (NRI). The primary endpoint was MACE, a composite of stroke, myocardial infarction, or death from coronary heart disease. Age interacted significantly with anthropometric measures and total-cholesterol on MACE (P ≤ 0.003), and therefore age-stratified analyses (<50 versus ≥ 50 years) were performed. BMI, WHR, EFM, and total-cholesterol were independently associated with MACE (P ≤ 0.003) and resulted in significantly positive NRI when added to age, sex, smoking status, and systolic blood pressure. Only total-cholesterol increased discrimination ability (AUCROC difference; P < 0.001). In subjects < 50 years, the prediction model with total-cholesterol was superior to the model including BMI, but not superior to models containing WHR or EFM, while in those ≥ 50 years, the model with total-cholesterol was superior to all models containing anthropometric variables, whether assessed individually or combined. We found a potential role for replacing total-cholesterol with anthropometric measures for MACE-prediction among individuals < 50 years when laboratory measurements are unavailable, but not among those ≥ 50 years.
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| 8. |
- Veronesi, Giovanni, et al.
(författare)
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Combined effect of educational status and cardiovascular risk factors on the incidence of coronary heart disease and stroke in European cohorts : implications for prevention
- 2017
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 24:4, s. 437-445
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Tidskriftsartikel (refereegranskat)abstract
- Background: The combined effect of social status and risk factors on the absolute risk of cardiovascular disease has been insufficiently investigated, but results provide guidance on who could benefit most through prevention.Methods: We followed 77,918 cardiovascular disease-free individuals aged 35-74 years at baseline, from 38 cohorts covering Nordic and Baltic countries, the UK and Central Europe, for a median of 12 years. Using Fine-Gray models in a competing-risks framework we estimated the effect of the interaction of education with smoking, blood pressure and body weight on the cumulative risk of incident acute coronary heart disease and stroke.Results: Compared with more educated smokers, the less educated had an added increase in absolute risk of cardiovascular disease of 3.1% ( 95% confidence interval+0.1%, +6.2%) in men and of 1.5% ( = 1.9%, +5.0%) in women, consistent across smoking categories. Conversely, the interaction was negative for overweight: -2.6% ( 95% CI: -5.6%, +0.3%) and obese: -3.6% ( -7.6%, +0.4%) men, suggesting that the more educated would benefit more from the same reduction in body weight. A weaker interaction was observed for body weight in women, and for blood pressure in both genders. Less educated men and women with a cluster of two or more risk factors had an added cardiovascular disease risk of 3.6% ( +0.1%, +7.0%) and of 2.6% ( - 0.5%, +5.6%), respectively, compared with their more educated counterparts.Conclusions: Socially disadvantaged subjects have more to gain from lifestyle and blood pressure modification, hopefully reducing both their risk and also social inequality in disease.
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| 9. |
- Veronesi, Giovanni, et al.
(författare)
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Decomposing the educational gradient in allostatic load across European populations. What matters the most : differentials in exposure or in susceptibility?
- 2020
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ Publishing Group Ltd. - 0143-005X .- 1470-2738. ; 74:12, s. 1008-1015
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Tidskriftsartikel (refereegranskat)abstract
- Background: We investigate whether socially disadvantaged individuals are more susceptible to the detrimental effects of smoking and alcohol intake on allostatic load (AL), a marker of physiological 'wear and tear', resulting from adaptation to chronic stress.Methods: In a cross-sectional analysis, 27 019 men and 26 738 women aged 35-74 years were identified from 21 European cohorts in the BiomarCaRE consortium. We defined three educational classes (EDs) according to years of schooling and an AL score as the sum of z-scores of eight selected biomarkers from the cardiovascular, metabolic and inflammatory systems. We used the Oaxaca-Blinder decomposition to disentangle the ED gradient in AL score into the differential exposure (DE, attributable to different distribution of smoking and alcohol intake across EDs) and the differential susceptibility (DS, attributable to a different effect of risk factors on AL across EDs) components.Results: Less-educated men (mean AL difference: 0.68, 95% CI 0.57 to 0.79) and women (1.52, 95% CI 1.40 to 1.64) had higher AL scores. DE accounted for 7% and 6% of the gradient in men and women, respectively. In men, combining smoking and alcohol intake, DS accounted for 42% of the gradient (smoking DS coefficient=0.177, 26% of the gradient; alcohol DS coefficient=0.109; 16%, not statistically significant). DS contribution increased to 69% in metabolic markers. DS estimates were consistent across age groups, irrespective of comorbidities and robust to unmeasured confounding. No DS was observed in women.Conclusions: In men, a DS mechanism substantially contributes to the educational class gradient in allostatic load.
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| 10. |
- Veronesi, Giovanni, et al.
(författare)
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Educational class inequalities in the incidence of coronary heart disease in Europe
- 2016
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 102:12, s. 958-965
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the burden of social inequalities in coronary heart disease (CHD) and to identify their major determinants in 15 European populations.Methods: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) study comprised 49 cohorts of middle-aged European adults free of CHD (110 928 individuals) recruited mostly in the mid-1980s and 1990s, with comparable assessment of baseline risk and follow-up procedures. We derived three educational classes accounting for birth cohorts and used regression-based inequality measures of absolute differences in CHD rates and HRs (ie, Relative Index of Inequality, RII) for the least versus the most educated individuals.Results: N=6522 first CHD events occurred during a median follow-up of 12 years. Educational class inequalities accounted for 343 and 170 additional CHD events per 100 000 person-years in the least educated men and women compared with the most educated, respectively. These figures corresponded to 48% and 71% of the average event rates in each gender group. Inequalities in CHD mortality were mainly driven by incidence in the Nordic countries, Scotland and Lithuania, and by 28-day case-fatality in the remaining central/South European populations. The pooled RIIs were 1.6 (95% CI 1.4 to 1.8) in men and 2.0 (1.7 to 2.4) in women, consistently across population. Risk factors accounted for a third of inequalities in CHD incidence; smoking was the major mediator in men, and High-Density-Lipoprotein (HDL) cholesterol in women.Conclusions: Social inequalities in CHD are still widespread in Europe. Since the major determinants of inequalities followed geographical and gender-specific patterns, European-level interventions should be tailored across different European regions.
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