| 1. |
- Magnussen, Christina, et al.
(författare)
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Global effect of modifiable risk factors on cardiovascular disease and mortality
- 2023
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 389:14, s. 1273-1285
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Tidskriftsartikel (refereegranskat)abstract
- Background: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking.Methods: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality.Results: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6).Conclusions: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.)
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| 2. |
- Ali, Imran, et al.
(författare)
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Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women.
- 2014
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Ingår i: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 134, s. 265-269
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Tidskriftsartikel (refereegranskat)abstract
- Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk.
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| 3. |
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| 4. |
- Engström, Annette
(författare)
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Cadmium as a risk factor for osteoporosis and fractures in women
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cadmium is toxic and accumulates in the body, particularly in the kidneys. Cereals, vegetables and potatoes are the main sources of exposure, besides tobacco smoking. The critical effect of cadmium is considered to be renal damage. Massive exposure is known to cause osteomalacia and osteoporosis with multiple fractures. A few recent studies have indicated that the exposure in the general population is associated with osteoporosis, but the link is not clear. The aim of this thesis was to investigate effects of long-term low-level cadmium exposure on bone health, and to explore whether these effects were mediated via reduced activation of 1,25(OH)2D (vitamin D) in the kidney. Another aim was to elucidate possible combined effects of cadmium and vitamin A (retinol) on bone health. Two population-based studies were used consisting of postmenopausal women, 54 to 69 years of age, with low cadmium exposure. Cadmium exposure was assessed by measuring cadmium concentrations in urine (as a biomarker of long-term exposure) and by estimating the dietary cadmium intake via a food frequency questionnaire. Total-body bone mineral density (BMD) and data on fracture incidence (1997-2009) were ascertained. Circulating levels of 1,25(OH)2D and retinol were measured in serum. Multivariable-adjusted inverse associations were observed between both urinary and dietary cadmium and BMD at the total body, femoral neck, total hip and lumbar spine. We also observed a statistically significant 2-3 fold increased risk of osteoporosis (T-score <-2.5) per µg/g creatinine of urinary cadmium, or per 10 µg/day of dietary cadmium. Among never-smokers, a several-fold statistically significant increased risk of any first fracture, first osteoporotic fracture and first distal forearm fracture was observed for urinary cadmium. A 30-50% statistically significantly increased risk of any first fracture were observed comparing high dietary cadmium intake (≥13 µg/day, median) with lower intakes (<13 µg/day) among all women and never-smokers, respectively. Combined high dietary and high urinary cadmium (≥0.50 µg/g creatinine) as compared to low, a 3-fold statistically significantly increased risk of osteoporosis and fractures were observed among never-smokers. Urinary cadmium was not associated with 1,25(OH)2D and there was no association between 1,25(OH)2D and markers of bone or kidney effects. This indicates that the negative association between low cadmium levels and BMD was not mediated via decreased circulating levels of active vitamin D. Serum retinol concentrations within the normal range tended to be associated with higher BMD at the distal forearm. Serum retinol concentrations in the upper normal range may counteract the negative effect of cadmium on bone. Altogether this thesis provides important evidence that cadmium exposure at the low exposure levels found in the Swedish general population is associated with negative effects on bone, as indicated by decreased BMD and an increased risk of osteoporosis and fractures. The findings are of high public health relevance since the main dietary cadmium exposure is via our most important foods, there are no signs of decreasing exposure levels, and that osteoporosis and related fractures are prevalent.
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| 5. |
- Engström, Annette, et al.
(författare)
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Long-term cadmium exposure and the association with bone mineral density and fractures in a population-based study among women
- 2011
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 26:3, s. 486-495
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: All people are exposed to cadmium (Cd) via food, smokers are additionally exposed. High Cd exposure is associated with severe bone damage, but the public health impact in relation to osteoporosis and fractures at low environmental exposure remains to be clarified. METHODS:: Within the population-based Swedish Mammography Cohort, we assessed urinary Cd (U-Cd, mug/g creatinine, cr) as a marker of life-time exposure and bone mineral density (BMD) by DXA among 2,688 women. Register-based information on fractures was retrieved from 1997 to 2009. Associations were evaluated by multivariable regression analyses. RESULTS:: In linear regression U-Cd was inversely associated with BMD at the total body (p<0.001), femoral neck (p=0.025), total hip (p=0.004), lumbar spine (p=0.088), and volumetric femoral neck (p=0.013). In comparison to women with U-Cd <0.50 mug/g cr, those with U-Cd >/=0.75 mug/g cr had OR 2.45 (95% CI, 1.51-3.97) and 1.97 (95% CI, 1.24-3.14) for osteoporosis at the femoral neck and lumbar spine, respectively. Among never-smokers, the corresponding ORs were 3.45 (95% CI, 1.46-8.23) and 3.26 (95% CI, 1.44-7.38). For any first fracture (n=395) OR was 1.16 (95% CI, 0.89-1.50) comparing U-Cd >/=0.5 mug/g cr with lower levels. Among never-smokers, the ORs (95% CIs) were 2.03 (1.33-3.09) for any first fracture, 2.06 (1.28-3.32) for first osteoporotic fracture, 2.18 (1.20-3.94) for first distal forearm fracture and 1.89 (1.25-2.85) for multiple incident fractures. CONCLUSIONS:: U-Cd at low environmental exposure from food in a general population of women showed modest but significant association with both BMD and fractures especially in never smokers indicating a larger concern than previously known.
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| 6. |
- Georgakis, Marios K., et al.
(författare)
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Association of Circulating Monocyte Chemoattractant Protein-1 Levels with Cardiovascular Mortality : A Meta-analysis of Population-Based Studies
- 2021
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Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 2380-6583. ; 6:5, s. 587-592
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. Objective: To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population. Data Sources and Selection: Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points. Data Extraction and Synthesis: Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses. Main Outcomes and Measures: Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes). Results: The meta-analysis included 7 cohort studies involving 21401 individuals (mean [SD] age, 53.7 [10.2] years; 10012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P =.01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P =.02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P <.001). In analyses comparing MCP-1 quartiles, these associations followed dose-response patterns. After additionally adjusting for vascular risk factors, the risk estimates were attenuated, but the associations of MCP-1 levels with cardiovascular death remained statistically significant, as did the association of MCP-1 levels in the upper quartile with coronary heart disease. There was no significant heterogeneity; the results did not change in sensitivity analyses excluding events occurring in the first 5 years after MCP-1 measurement, and the risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity C-reactive protein. Conclusions and Relevance: Higher circulating MCP-1 levels are associated with higher long-term cardiovascular mortality in community-dwelling individuals free of overt cardiovascular disease. These findings provide further support for a key role of MCP-1-signaling in cardiovascular disease..
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| 7. |
- Georgakis, Marios K., et al.
(författare)
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Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke : Meta-Analysis of Population-Based Studies Involving 17 180 Individuals
- 2019
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Ingår i: Circulation Research. - 0009-7330. ; 125:8, s. 773-782
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01-1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02-1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82-1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00-1.42]; third quartile: 1.35 [1.14-1.59]; fourth quartile: 1.38 [1.07-1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Conclusions: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.
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| 8. |
- Magnussen, Christina, et al.
(författare)
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Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality
- 2023
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 389:14, s. 1273-1285
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Tidskriftsartikel (refereegranskat)abstract
- Background Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking.Methods We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality.Results Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6).Conclusions Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.)Harmonized individual-level data from a global cohort showed that more than half the cases of incident cardiovascular disease and one fifth of deaths may be attributable to five modifiable risk factors.
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| 9. |
- Tarp, Julie Bjerre, et al.
(författare)
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Subclinical atherosclerosis in patients with cyanotic congenital heart disease
- 2019
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 277, s. 97-103
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Survival in patients with cyanotic congenital heart disease (CCHD) has improved dramatically. The result is an ageing population with risk of acquired heart disease. Previous small uncontrolled studies suggested that these patients are protected against the development of atherosclerosis. To test this hypothesis, we sought to determine the prevalence of subclinical atherosclerosis in a larger population of patients with CCHD. Method: We compared the prevalence of subclinical atherosclerosis in adult CCHD patients from Denmark, Sweden, Norway and Australia, with that in age-, sex-, smoking status-, and body mass index matched controls. Coronary artery atherosclerosis was assessed on computed tomography with coronary artery calcification (CAC) score. Subclinical atherosclerosis was defined by CAC-score > 0. Carotid artery atherosclerosis was evaluated using ultrasound by measuring carotid plaque thickness (cPT-max) and carotid intima media thickness (CIMT). Lipid status was evaluated as an important atherosclerotic risk factor. Results: Seventy-four patients with CCHD (57% women, median age 49.5 years) and 74 matched controls (57% women, median age 50.0 years) were included. There were no differences between the groups in: CAC-score > 0 (21% vs. 19%, respectively; p = 0.8), carotid plaques (19% vs. 9%, respectively; p = 0.1), cPT-max (2.3 mm vs. 2.8 mm, respectively; p = 0.1) or CIMT (0.61 mm vs. 0.61 mm, respectively; p = 0.98). And further no significant differences in lipoprotein concentrations measured by ultracentrifugation. Conclusion: Young adults with CCHD have similar cardiovascular risk factor profiles and measures of subclinical atherosclerosis, compared with controls. Given their increasing life expectancies, athero-preventive strategies should be an important part of their clinical management.
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| 10. |
- Tarp, Julie Bjerre, et al.
(författare)
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Vascular function in adults with cyanotic congenital heart disease
- 2020
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Ingår i: IJC Heart and Vasculature. - : Elsevier BV. - 2352-9067. ; 30
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with cyanotic congenital heart disease (CCHD) may have a low burden of atherosclerosis. Endothelial dysfunction is an early stage of atherosclerosis and endothelial function is previously studied in smaller CCHD groups with different techniques and variable results. We aimed to examine endothelial function and carotid atherosclerosis in a larger group of CCHD patients. Methods: This multicentre study assessed endothelial function in adults with CCHD and controls by measuring the dilatory response of the brachial artery to post-ischemic hyperaemia (endothelium-dependent flow-mediated-vasodilatation (FMD)), and to nitroglycerin (endothelium-independent nitroglycerin-induced dilatation (NID)). Flow was measured at baseline and after ischaemia (reactive hyperaemia). Carotid-intima-media-thickness (CIMT), prevalence of carotid plaque and plaque thickness (cPT-max) were evaluated ultrasonographically. Lipoproteins, inflammatory and vascular markers, including sphingosine-1-phosphate (S1P) were measured. Results: Forty-five patients with CCHD (median age 50 years) and 45 matched controls (median age 52 years) were included. The patients presented with lower reactive hyperaemia (409 ± 114% vs. 611 ± 248%, p < 0.0001), however preserved FMD response compared to controls (106.5 ± 8.3% vs. 106.4 ± 6.1%, p = 0.95). In contrast, NID was lower in the patients (110.5 ± 6.1% vs. 115.1 ± 7.4%, p = 0.053). There was no difference in CIMT, carotid plaque or cPT-max. The patients presented with lower high-density-lipoprotein cholesterol, and higher level of inflammatory markers and S1P. Conclusion: Adults with CCHD had preserved FMD in the brachial artery, but impaired NID response and lower reactive hyperaemia than controls. The preserved FMD and the comparable prevalence of carotid atherosclerosis indicate that CCHD patients have the same risk of atherosclerosis as controls.
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