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Sökning: WFRF:(Roy Carine)

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1.
  • Borghi, Claudio, et al. (författare)
  • Lack of control of hypertension in primary cardiovascular disease prevention in Europe : Results from the EURIKA study
  • 2016
  • Ingår i: International Journal of Cardiology. - 0167-5273 .- 1874-1754. ; 218, s. 83-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prevalence of and factors associated with uncontrolled hypertension and apparent resistant hypertension were assessed in the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA; NCT00882336). Methods: EURIKA was a cross-sectional observational study including patients being treated for the primary prevention of cardiovascular disease in 12 European countries. Patients were assessed if they were being treated for hypertension (N = 5220). Blood pressure control was defined according to European guidelines, with sensitivity analysis taking account of patients' age and diabetes status. Associated factors were assessed using multivariate analysis. Results: In the primary analysis, a total of 2691 patients (51.6%) had uncontrolled hypertension. Factors significantly associated with an increased risk of having uncontrolled hypertension included female sex (odds ratio [OR]: 2.29; 95% confidence interval [CI]: 1.93-2.73), body mass index (BMI; OR per kg/m(2): 1.03; 95% CI: 1.01-1.04), and geographic location. A total of 749 patients (14.3%) had apparent resistant hypertension. Factors significantly associated with an increased risk of having apparent resistant hypertension included BMI (OR per kg/m(2): 1.06; 95% CI: 1.04-1.08), diabetes (OR: 1.28; 95% CI: 1.06-1.53), use of statins (OR: 1.36; 95% CI: 1.15-1.62), serum uric acid levels (OR: 1.16; 95% CI: 1.09-1.23), and geographic location. Similar results were seen in sensitivity analyses. Conclusions: Over 50% of patients treated for hypertension continued to have uncontrolled blood pressure and 14.3% had apparent resistant hypertension. Positive associations were seen with other cardiovascular risk factors. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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2.
  • Borghi, Claudio, et al. (författare)
  • Serum uric acid levels are associated with cardiovascular risk score : A post hoc analysis of the EURIKA study
  • 2018
  • Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 253, s. 167-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Reports are conflicting on whether serum uric acid (sUA) levels are independently associated with increased cardiovascular (CV) death risk. Methods: This post hoc analysis assessed the relationship between sUA levels and CV death risk score in 7531 patients from the cross-sectional, multinational EURIKA study (NCT00882336). Patients had at least one CV risk factor but no clinical CV disease. Ten-year risk of CV death was estimated using SCORE-HDL and SCORE algorithms, categorized as low (<1%), intermediate (1% to <5%), high (>5% to <10%) or very high (>10%). Results: Mean serum sUA levels increased significantly with increasing CV death risk category in the overall population and in subgroups stratified by diuretics use or renal function (all P < 0.0001). Multivariate ordinal logistic regression analyses, adjusted for factors significantly associated with CV death risk in univariate analyses (study country, body mass index, number of CV risk factors and comorbidities, use of lipid lowering therapies, antihypertensives and antidiabetics), showed a significant association between sUA levels and SCORE-HDL category in the overall population (OR: 1.39 [95% CI: 1.34-1.44]) and all subgroups (using diuretics: 1.32 [1.24-1.40]; not using diuretics: 1.46 [1.39-1.53]; estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m(2): 1.30 [1.22-1.38]; eGFR >= 60 ml/min/1.73 m(2): 1.44 [1.38-1.51]; all P < 0.0001). Similar results were obtained when using SCORE. Conclusions: Higher sUA levels are associated with progressively higher 10-year CV death risk score in patients with at least one CV risk factor but no CV disease. (c) 2017 Elsevier B.V. All rights reserved.
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3.
  • Borghi, Claudio, et al. (författare)
  • The association between blood pressure and lipid levels in Europe : European study on cardiovascular risk prevention and management in usual daily practice
  • 2016
  • Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 34:11, s. 2155-2163
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives:Several studies have suggested a positive association between serum lipid levels and blood pressure (BP). This study investigated this association in a large population from 12 European countries.Methods:Data were taken from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (ClinicalTrials.gov identifier: NCT00882336). Associations between BP and lipid levels in patients free from cardiovascular disease and with at least one major cardiovascular disease risk factor (N=7641) were assessed using linear regression analyses.Results:Overall, 72.8 and 64.8% of patients had hypertension and dyslipidaemia, respectively; 47.0% had both conditions. Regression coefficients (95% confidence interval) for the associations of LDL cholesterol, non-HDL cholesterol, total cholesterol and apolipoprotein B levels with SBP, adjusted for age, sex and BMI, were 0.93mmHg/mmol per l (0.54-1.31), 1.07mmHg/mmol per l (0.73-1.40), 1.02mmHg/mmol per l (0.69-1.35) and 4.94mmHg/g per l (3.43-6.46), respectively. The corresponding values (95% confidence interval) for the associations with DBP were 0.96mmHg/mmol per l (0.73-1.19), 0.95mmHg/mmol per l (0.75-1.15), 0.87mmHg/mmol per l (0.67-1.07) and 4.33mmHg/g per l (3.42-5.23), respectively. Most of these associations remained significant whether patients were treated with statins or not.Conclusion:Small but statistically significant associations between lipid levels and BP were observed in a large, multinational European population. Further research is warranted to assess the causality of this association and its implications on the management of patients with both hypertension and dyslipidaemia.
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4.
  • Halcox, Julian P. J., et al. (författare)
  • C-reactive protein levels in patients at cardiovascular risk : EURIKA study
  • 2014
  • Ingår i: BMC Cardiovascular Disorders. - 1471-2261 .- 1471-2261. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Elevated C-reactive protein (CRP) levels are associated with high cardiovascular risk, and might identify patients who could benefit from more carefully adapted risk factor management. We have assessed the prevalence of elevated CRP levels in patients with one or more traditional cardiovascular risk factors. Methods: Data were analysed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials. gov Identifier: NCT00882336), which included patients (aged = 50 years) from 12 European countries with at least one traditional cardiovascular risk factor but no history of cardiovascular disease. Analysis was also carried out on the subset of patients without diabetes mellitus who were not receiving statin therapy. Results: In the overall population, CRP levels were positively correlated with body mass index and glycated haemoglobin levels, and were negatively correlated with high- density lipoprotein cholesterol levels. CRP levels were also higher in women, those at higher traditionally estimated cardiovascular risk and those with greater numbers of metabolic syndrome markers. Among patients without diabetes mellitus who were not receiving statin therapy, approximately 30% had CRP levels >= 3 mg/ L, and approximately 50% had CRP levels = 2 mg/ L, including those at intermediate levels of traditionally estimated cardiovascular risk. Conclusions: CRP levels are elevated in a large proportion of patients with at least one cardiovascular risk factor, without diabetes mellitus who are not receiving statin therapy, suggesting a higher level of cardiovascular risk than predicted according to conventional risk estimation systems.
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5.
  • Halcox, Julian P., et al. (författare)
  • Low Rates of Both Lipid-Lowering Therapy Use and Achievement of Low-Density Lipoprotein Cholesterol Targets in Individuals at High-Risk for Cardiovascular Disease across Europe
  • 2015
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To analyse the treatment and control of dyslipidaemia in patients at high and very high cardiovascular risk being treated for the primary prevention of cardiovascular disease (CVD) in Europe. Methods and Results Data were assessed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov identifier: NCT00882336), which included a randomly sampled population of primary CVD prevention patients from 12 European countries (n = 7641). Patients' 10-year risk of CVD-related mortality was calculated using the Systematic Coronary Risk Evaluation (SCORE) algorithm, identifying 5019 patients at high cardiovascular risk (SCORE >= 5% and/or receiving lipid-lowering therapy), and 2970 patients at very high cardiovascular risk (SCORE >= 10% or with diabetes mellitus). Among high-risk individuals, 65.3% were receiving lipid-lowering therapy, and 61.3% of treated patients had uncontrolled low-density lipoprotein cholesterol (LDL-C) levels (>= 2.5 mmol/L). For very-high-risk patients (uncontrolled LDL-C levels defined as >= 1.8 mmol/L) these figures were 49.5% and 82.9%, respectively. Excess 10-year risk of CVD-related mortality (according to SCORE) attributable to lack of control of dyslipidaemia was estimated to be 0.72% and 1.61% among high-risk and very-high-risk patients, respectively. Among high-risk individuals with uncontrolled LDL-C levels, only 8.7% were receiving a high-intensity statin (atorvastatin >= 40 mg/day or rosuvastatin >= 20 mg/day). Among very-high-risk patients, this figure was 8.4%. Conclusions There is a considerable opportunity for improvement in rates of lipid-lowering therapy use and achievement of lipid-level targets in high-risk and very-high-risk patients being treated for primary CVD prevention in Europe.
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6.
  • Halcox, Julian P., et al. (författare)
  • Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe : EURIKA, a cross-sectional observational study
  • 2017
  • Ingår i: BMC Cardiovascular Disorders. - : BioMed Central. - 1471-2261 .- 1471-2261. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Atherogenic dyslipidemia is associated with poor cardiovascular outcomes, yet markers of this condition are often ignored in clinical practice. Here, we address a clear evidence gap by assessing the prevalence and treatment of two markers of atherogenic dyslipidemia: elevated triglyceride levels and low levels of high-density lipoprotein cholesterol. Methods: This cross-sectional observational study assessed the prevalence of two atherogenic dyslipidemia markers, high triglyceride levels and low high-density lipoprotein cholesterol levels, in the study population from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA; N = 7641; of whom 51.6% were female and 95.6% were White/Caucasian). The EURIKA population included European patients, aged at least 50 years with at least one cardiovascular risk factor but no history of cardiovascular disease. Results: Over 20% of patients from the EURIKA population have either triglyceride or high-density lipoprotein cholesterol levels characteristic of atherogenic dyslipidemia. Furthermore, the proportions of patients with one of these markers were higher in subpopulations with type 2 diabetes mellitus or those already calculated to be at high risk of cardiovascular disease. Approximately 55% of the EURIKA population who have markers of atherogenic dyslipidemia are not receiving lipid-lowering therapy. Conclusions: A considerable proportion of patients with at least one major cardiovascular risk factor in the primary cardiovascular disease prevention setting have markers of atherogenic dyslipidemia. The majority of these patients are not receiving optimal treatment, as specified in international guidelines, and thus their risk of developing cardiovascular disease is possibly underestimated.
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7.
  • Lukanova, Annekatrin, et al. (författare)
  • Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.
  • 2004
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 108:3, s. 425-432
  • Tidskriftsartikel (refereegranskat)abstract
    • Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis.
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8.
  • Lukanova, Annekatrin, et al. (författare)
  • Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.
  • 2004
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 108:2, s. 262-268
  • Tidskriftsartikel (refereegranskat)abstract
    • Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.
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9.
  • Windpassinger, Christian, et al. (författare)
  • CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays
  • Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297. ; 101:3, s. 391-403
  • Tidskriftsartikel (refereegranskat)abstract
    • In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal development.
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