11. |
- Gohar, Aisha, et al.
(författare)
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Circulating GDF-15 levels predict future secondary manifestations of cardiovascular disease explicitly in women but not men with atherosclerosis
- 2017
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 241, s. 430-436
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated serum levels of growth differentiation factor-15 (GDF-15), is an established risk factor for a range of cardiovascular diseases.We aimed to evaluate the predictive value of plasma GDF-15 as a biomarker for secondary cardiovascular events (CVE) in patients with atherosclerosis undergoing carotid endarterectomy (CEA). Secondly, we determined whether plasma GDF-15 was associated with carotid plaque characteristics. Methods: Circulating GDF-15 levels were determined by Luminex assay in a cohort of 1056 patients from the Athero-Express biobank. Composite endpoint was defined as major CVE, death and peripheral vascular interventions. Findings were validated in 473 patients from the independent Carotid Plaque Imaging Project biobank. Results: GDF-15 levels did not associate with secondary CVE in the total cohort. However, following a significant interaction with sex, it was found to be strongly, independently predictive of secondary CVE in women but not men (quartile 4 vs. quartile 1: HR 3.04 [95% CI 1.35-6.86], p = 0.007 in women vs. HR 0.96 [95% CI 0.66-1.40], p = 0.845 in men). This was also observed in the validation cohort (women: HR 2.28 [95% CI 1.04-5.05], p = 0.041), albeit dependent upon renal function. In addition, GDF-15 was associated with the presence of plaque smooth muscle cells and calcification. Conclusion: High circulating GDF-15 levels are predictive of secondary CVE in women but not in men with carotid atherosclerotic disease undergoing CEA, suggesting a potential use for GDF-15 as a biomarker for secondary prevention in women. Sex differences in the role of GDF-15 in atherosclerotic disease deserve further interest.
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12. |
- Magnussen, Christina, et al.
(författare)
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Sex Differences and Similarities in Atrial Fibrillation Epidemiology, Risk Factors, and Mortality in Community Cohorts Results From the BiomarCaRE Consortium (Biomarker for Cardiovascular Risk Assessment in Europe)
- 2017
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 136:17, s. 1588-1597
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atrial fibrillation (AF) is a common cardiac disease in aging populations with high comorbidity and mortality. Sex differences in AF epidemiology are insufficiently understood.Methods: In N=79 793 individuals without AF diagnosis at baseline (median age, 49.6 years; age range, 24.1–97.6 years; 51.7% women) from 4 community-based European studies (FINRISK, DanMONICA, Moli-sani Northern Sweden) of the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), we examined AF incidence, its association with mortality, common risk factors, biomarkers, and prevalent cardiovascular disease, and their attributable risk by sex. Median follow-up time was 12.6 (to a maximum of 28.2) years.Results: Fewer AF cases were observed in women (N=1796; 4.4%), than in men (N=2465; 6.4%). Cardiovascular risk factor distribution and lipid profile at baseline were less beneficial in men than in women, and cardiovascular disease was more prevalent in men. Cumulative incidence increased markedly after the age of 50 years in men and after 60 years in women. The lifetime risk was similar (>30%) for both sexes. Subjects with incident AF had a 3.5-fold risk of death in comparison with those without AF. Multivariable-adjusted models showed sex differences for the association of body mass index and AF (hazard ratio per standard deviation increase, 1.18; 95% confidence interval [CI], 1.12–1.23 in women versus 1.31; 95% CI 1.25–1.38 in men; interaction P value of 0.001). Total cholesterol was inversely associated with incident AF with a greater risk reduction in women (hazard ratio per SD, 0.86; 95% CI, 0.81–0.90 versus 0.92; 95% CI, 0.88–0.97 in men; interaction P value of 0.023). No sex differences were seen for C-reactive protein and N-terminal pro B-type natriuretic peptide. The population-attributable risk of all risk factors combined was 41.9% in women and 46.0% in men. About 20% of the risk was observed for body mass index.Conclusions: Lifetime risk of AF was high, and AF was strongly associated with increased mortality both in women and men. Body mass index explained the largest proportion of AF risk. Observed sex differences in the association of body mass index and total cholesterol with AF need to be evaluated for underlying pathophysiology and relevance to sex-specific prevention strategies.
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13. |
- Magnussen, Christina, et al.
(författare)
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Sex-Specific Epidemiology of Heart Failure Risk and Mortality in Europe Results From the BiomarCaRE Consortium
- 2019
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Ingår i: JACC. Heart failure. - : ELSEVIER SCI LTD. - 2213-1779 .- 2213-1787. ; 7:3, s. 204-213
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES This study investigates differences between women and men in heart failure (HF) risk and mortality. BACKGROUND Sex differences in HF epidemiology are insufficiently understood. METHODS In 78,657 individuals (median 49.5 years of age; age range 24.1 to 98.7 years; 51.7% women) from community-based European studies (FINRISK, DanMONICA, Moli-sani, Northern Sweden) of the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium, the association between incident HF and mortality, the relationship of cardiovascular risk factors, prevalent cardiovascular diseases, biomarkers (C-reactive protein [CRP]; N-terminal pro-B-type natriuretic peptide [NT-proBNP]) with incident HF, and their attributable risks were tested in women vs. men. RESULTS Over a median follow-up of 12.7 years, fewer HF cases were observed in women (n = 2,399 [5.9%]) than in men (n = 2,771 [7.3%]). HF incidence increased markedly after 60 years of age, initially with a more rapid increase in men, whereas incidence in women exceeded that of men after 85 years of age. HF onset substantially increased mortality risk in both sexes. Multivariable-adjusted Cox models showed the following sex differences for the association with incident HF: systolic blood pressure hazard ratio (HR) according to SD in women of 1.09 (95% confidence interval [CI]: 1.05 to 1.14) versus HR of 1.19 (95% CI: 1.14 to 1.24) in men; heart rate HR of 0.98 (95% CI: 0.93 to 1.03) in women versus HR of 1.09 (95% CI: 1.04 to 1.13) in men; CRP HR of 1.10 (95% CI: 1.00 to 1.20) in women versus HR of 1.32 (95% CI: 1.24 to 1.41) in men; and NT-proBNP HR of 1.54 (95% CI: 1.37 to 1.74) in women versus HR of 1.89 (95% CI: 1.75 to 2.05) in men. Population-attributable risk of all risk factors combined was 59.0% in women and 62.9% in men. CONCLUSIONS Women had a lower risk for HF than men. Sex differences were seen for systolic blood pressure, heart rate, CRP, and NT-proBNP, with a lower HF risk in women.
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14. |
- van der Laan, Sander W., et al.
(författare)
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Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study
- 2016
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 68:9, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.
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15. |
- Dullemeijer, Carla, et al.
(författare)
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Differences in fatty acid composition between cerebral brain lobes in juvenile pigs after fish oil feeding
- 2008
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 100:4, s. 794-800
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Tidskriftsartikel (refereegranskat)abstract
- Very long-chain n-3 PUFA from fish are suggested to play a role in the development of the brain. Fish oil feeding results in higher proportions of n-3 PUFA in the brains of newborn piglets. However, the effect of fish oil on the fatty acid composition of specific cerebral brain lobes in juvenile pigs is largely uninvestigated. This study examined the effect of a fish oil diet on the fatty acid composition of the frontal, parietal, temporal and occipital brain lobes in juvenile pigs (7 weeks old). Pigs were randomly allocated to a semipurified pig diet containing either 4% (w/w) fish oil (n 19) or 4% (w/w) high-oleic acid sunflower oil (HOSF diet, n 18) for a period of 8 weeks. The fish oil diet resulted in significantly higher proportions (%) of DHA in the frontal (10.6 (SD1.2)), parietal (10.2 (SD1.5)) and occipital brain lobes (9.9 (SD 1.3)), but not in the temporal lobe (7.7 (SD1.6)), compared with pigs fed the HOSF diet (frontal lobe, 7.5 (SD1.0); parietal lobe, 8.1 (SD 1.3); occipital lobe, 7.3 (SD1.2), temporal lobe, 6.6 (SD1.2). Moreover, the proportion of DHA was significantly lower in the temporal lobe compared with the frontal, parietal and occipital brain lobes in pigs fed a fish oil diet. In conclusion, the brains of juvenile pigs appear to be responsive to dietary fish oil, although the temporal brain lobe is less responsive compared with the other three brain lobes. The functional consequences of these differences are a challenging focus for future investigation.
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16. |
- Lind, Lars, et al.
(författare)
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Effect of Rosuvastatin on the Echolucency of the Common Carotid Intima-Media in Low-Risk Individuals : the METEOR Trial
- 2012
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Ingår i: Journal of the American Society of Echocardiography. - : Elsevier BV. - 0894-7317 .- 1097-6795. ; 25:10, s. 1120-1127.e1
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Tidskriftsartikel (refereegranskat)abstract
- Background:The echolucency of the carotid intima-media is related to increased cardiovascular risk factor levels, morbidity, and mortality. The aim of this study was to assess the effect of statins on the echolucency of the common carotid intima-media in a low-risk population.Methods:Data from the Measuring Effects on Intima-Media Thickness: An Evaluation of Rosuvastatin study were used. Ultrasound images from the far walls of the left and right common carotid arteries were used for evaluation of the echolucency of the carotid intima-media, measured by grayscale median (GSM). Low GSM values reflect echolucent structures, whereas high values reflect echogenic structures. The primary end point was the difference in the annual rate of change in GSM between rosuvastatin and placebo.Results:Two-year change in GSM did not significantly differ between rosuvastatin and placebo in the total population, with a mean difference in the rate of change in GSM of 1.13 (95% confidence interval, -1.00 to 3.25). The effect of rosuvastatin differed across quintiles of baseline GSM values (P for interaction = .01). In the lowest quintile (n = 175) (i.e., in those with the most echolucent intima-media), the difference in the rate of change in GSM between rosuvastatin and placebo was 4.18 (95% confidence interval, -0.23 to 8.58). Increases in GSM were significantly related to decreasing low-density lipoprotein cholesterol levels in the lowest quintile (beta = 0.76; 95% confidence interval, 0.26 to 1.25).Conclusions:Treatment with rosuvastatin did not affect the echolucency of the arterial wall in all low-risk individuals. However, a potential effect of rosuvastatin on the echolucency of the common carotid intima-media is most likely to be found in individuals with echolucent arterial walls at baseline.
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17. |
- Peters, Sanne A. E., et al.
(författare)
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The impact of variability in ultrasound settings on the measured echolucency of the carotid intima-media
- 2013
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 31:9, s. 1861-1867
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Tidskriftsartikel (refereegranskat)abstract
- Background:B-mode ultrasound measurements of the echolucency of the carotid intima-media may hold information on cardiovascular risk. The information obtained from this measurement may depend on which gain settings are used. We studied the effect of gain settings on echolucency measurements and its consequences on risk factor relations and treatment effects.Methods:We used two approaches. In the first, we examined the relationship between calibration, gain and common grey-scale median (GSM) from repeated ultrasound images obtained from four healthy individuals at gain settings ranging from -20 to 20dB. In the second, we evaluated the effect of gain settings on the relation of risk factors and statin treatment with common GSM, using images from 325 participants of the Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin (METEOR) study with documented gain settings. Echolucency of the carotid intima-media was measured from ultrasound images using PaintShop Pro and Artery Measurement Software and expressed as GSM.Results:In healthy individuals, common GSM increased with increments in gain setting, primarily when the measurements were not calibrated. In the METEOR study sample, age and sex were significantly related to gain setting. The risk factor relations with common GSM were of the same magnitude and direction after adjustment for gain setting. Furthermore, adjustment for gain setting did not alter the rates of GSM change over time.Conclusion:Extreme variability in gain settings has a major impact on the echolucency measurements of the far wall common carotid intima-media. Calibration should be used to adjust for these effects of gain settings. Variability in gain settings, however, seems limited in real practice and did not change the direction and magnitude of the relations under study. However, as age and sex are major determinants of gain settings, adjustment for or stratification by age and sex is recommended in studies into echolucency of the carotid intima-media in situations in which gain settings are unknown.
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