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1.
Lancet ; 394(10215): 2173-2183, 2019 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-31810609

RESUMO

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Medição de Risco/métodos , Adulto , Idoso , Austrália/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia
2.
J Hypertens ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31764589

RESUMO

OBJECTIVE: Although the causality of the obesity--hypertension association is established, the potential for prevention is not. We hypothesized that weight gain between early adulthood and mid-life is associated with higher mid-life blood pressure. METHODS: We investigated the hypothesis using a large contemporaneous population-based mid-life cohort of men and women aged 50-64 years. Recalled body weight at age 20 years was self-reported, and mid-life body weight and office blood pressures were measured in accordance with a detailed protocol. RESULTS: On average, men had gained 14.9 (95% CI 14.6-15.2) kg of weight, and women 14.6 (95% CI 14.4-14.9) kg, between age 20 years and the mid-life examination, corresponding to 0.40 (95% CI 0.39-0.41) kg/year for men and women. Both weight at age 20 years and weight at the mid-life examination were associated with mid-life blood pressures. On average, a 10 kg weight increase between age 20 years and mid-life was associated with 2.2 (95% CI 0.9-3.5) mmHg higher systolic and 1.7 (95% CI 0.9-2.5) mmHg higher diastolic mid-life blood pressure in men, and 3.2 (2.5-4.0) mmHg higher systolic and 2.4 (1.9-2.9) mmHg higher diastolic mid-life blood pressure in women. Mid-life weight was more closely associated than weight at age 20 years with mid-life blood pressure. For a given mid-life weight, blood pressure was higher in persons with higher weight gain from age 20 years. CONCLUSION: In sum, weight gain between early adulthood and mid-life was associated with higher mid-life blood pressure. The magnitude of the association indicates a potentially great public health impact of strategies to prevent weight gain throughout adulthood.

3.
Europace ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740944

RESUMO

AIMS: Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality. METHODS AND RESULTS: Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 individuals, median age 46.1 (25th-75th percentile 35.8-57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 individuals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17-7.54; P < 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90-5.00; P < 0.001). CONCLUSION: The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes.

4.
Eur J Nutr ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754783

RESUMO

PURPOSE: Vitamin D, produced through cutaneous photosynthesis or ingested via foods or supplements, has generated considerable research interest due to its potential health effects. However, epidemiological data on the time trends of vitamin D status are sparse, especially from northern Europe. We examined the time trend of vitamin D concentrations in northern Sweden between 1986 and 2014. METHODS: We used data on 11,129 men and women (aged 25-74 years) from seven population-based surveys (the Northern Sweden MONICA study), recruited between 1986 and 2014. Serum vitamin D (25-hydroxyvitamin D) status was measured using a one-step immunoassay (Abbott Architect). Multivariable linear regression models, adjusted for age, sex, and a number of other variables, were used to estimate the time trend of vitamin D concentrations. RESULTS: The mean value of vitamin D in the entire study population was 19.9 ng/mL [standard deviation (SD) 7.9], with lower values in men (19.4 ng/mL; SD 7.5) than in women (20.5 ng/mL; SD 8.2). Using the survey in 1986 as reference category, the multivariable-adjusted mean difference [95% confidence interval (CI)] in ng/mL was 2.7 (2.2, 3.3) in 1990, 3.2 (2.7, 3.7) in 1994, 1.6 (1.0, 2.1) in 1999, - 2.0 (- 2.5, - 1.4) in 2004, 1.0 (0.4, 1.5) in 2009, and 3.1 (2.5, 3.6) in 2014. CONCLUSION: In this large cross-sectional study, we observed no clear upward or downward trend of vitamin D concentrations in northern Sweden between 1986 and 2014.

5.
Scand J Clin Lab Invest ; 79(7): 524-530, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522562

RESUMO

Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFRcystatin C and eGFRcreatinine and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFRcystatin C and eGFRcreatinine. A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73-0.97]), especially in women (0.74 [0.60-0.92] vs. 0.93 [0.76-1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44-0.83] and 0.89 [0.65-1.23], respectively). In conclusion, a high ratio between eGFRcystatin C and eGFRcreatinine was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.

6.
Thorax ; 74(10): 958-964, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31434752

RESUMO

INTRODUCTION: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m2) is rapidly increasing globally and its impact on breathlessness is unclear. METHODS: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score ≥1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. RESULTS: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m2; and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. CONCLUSION: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

7.
Int J Epidemiol ; 48(6): 2018-2025, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31363756

RESUMO

BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium. METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries. RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH. CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.

8.
Eur J Endocrinol ; 181(4): 429-438, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325907

RESUMO

Objective: The identification of new causal risk factors has the potential to improve cardiovascular disease (CVD) risk prediction and the development of new treatments to reduce CVD deaths. In the general population, we sought to determine whether cortisol is a causal risk factor for CVD and coronary heart disease (CHD). Design and methods: Three approaches were adopted to investigate the association between cortisol and CVD/CHD. First, we used multivariable regression in two prospective nested case-control studies (total 798 participants, 313 incident CVD/CHD with complete data). Second, a random-effects meta-analysis of these data and previously published prospective associations was performed (total 6680 controls, 696 incident CVD/CHD). Finally, one- and two-sample Mendelian randomization analyses were performed (122,737 CHD cases, 547,261 controls for two-sample analyses). Results: In the two prospective nested case-control studies, logistic regression adjusting for sex, age, BMI, smoking and time of sampling, demonstrated a positive association between morning plasma cortisol and incident CVD (OR: 1.28 per 1 SD higher cortisol, 95% CI: 1.06-1.54). In the meta-analysis of prospective studies, the equivalent result was OR: 1.18, 95% CI: 1.06-1.31. Results from the two-sample Mendelian randomization were consistent with these positive associations: OR: 1.06, 95% CI: 0.98-1.15. Conclusions: All three approaches demonstrated a positive association between morning plasma cortisol and incident CVD. Together, these findings suggest that elevated morning cortisol is a causal risk factor for CVD. The current data suggest strategies targeted at lowering cortisol action should be evaluated for their effects on CVD.

9.
N Engl J Med ; 380(26): 2529-2540, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31242362

RESUMO

BACKGROUND: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. METHODS: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. RESULTS: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. CONCLUSIONS: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Medição de Risco/métodos , Troponina/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Troponina I/sangue
10.
J Hypertens ; 37(8): 1699-1704, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31058795

RESUMO

OBJECTIVES: As intervention studies have shown a reduction in body weight to be paralleled with a reduction in left ventricular mass (LVM), we quantified a hypothesized causal relationship between fat mass and LVM, and how much of these effects that was mediated by blood pressure (BP), diabetes and adipokines. Also visceral and subcutaneous adipose tissue (VAT and SAT) were explored in the same fashion. METHODS: In the Prospective Study of the Vasculature in Uppsala Seniors study (n = 1016, 50% women, all aged 70 years), LVM was measured by echocardiography (indexed for lean mass, LVMI), fat and lean mass by dual-energy X-ray. VAT and SAT were measured by abdominal MRI (in n = 275). RESULTS: In a structural equation model adjusting for sex, the total effect of fat mass on LVMI was large (standardized coefficient 0.280, P = 3.2 × 10, 95% confidence interval 0.210-0.349). Out of the total effect of fat mass on LVMI, 29.0% was mediated by BP and glucose (P = 2.4 × 10). The BP pathway was most important, mediating 24.4% of the total effect of fat mass on LVMI (P = 4.6 × 10), while the glucose pathway accounted for 4.6% (P = 0.033). The association of VAT with LVMI (0.202, P = 2.4 × 10) was slightly weaker than that of SAT with LVMI (0.283, P = 1.0 × 10). Of several measured adipokines, leptin was a significant mediator of the effect of fat mass on LVMI (P = 3.0 × 10). CONCLUSION: One-third of the hypothesized association between body fat and LVMI was mediated by BP and glucose in this population-based cohort. Leptin was also an important mediator. Visceral adipose tissue was not more closely related to LVMI than subcutaneous abdominal fat.

11.
Scand Cardiovasc J ; 53(2): 91-97, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31109205

RESUMO

OBJECTIVES: Due to age-related differences in aortic valve structure, it is likely that the pathophysiology of aortic stenosis (AS) and associated risk factors differ between age groups. Here we prospectively studied the influence of traditional cardiovascular risk factors on AS development requiring surgery among patients without concomitant coronary artery disease (CAD) and stratified for age. DESIGN: This study included 322 patients, who had prior to surgery for AS participated in population-based surveys, and 131 of them had no visible CAD upon preoperative coronary angiogram. For each case, we selected four referents matched for age, gender, and geographic area. To identify predictors for surgery, we used multivariable conditional logistic regression with a model including arterial hypertension (or measured blood pressure and antihypertensive medication), cholesterol levels, diabetes, body mass index (BMI), and smoking. RESULTS: In patients without CAD, future surgery for AS was associated with arterial hypertension and elevated levels of diastolic blood pressure in patients younger than 60 years at surgery (odds ratio [95% confidence interval]), (3.40 [1.45-7.93] and 1.60 [1.09-2.37], respectively), and with only impaired fasting glucose tolerance in patients 60 years or older at surgery (3.22 [1.19-8.76]). CONCLUSION: Arterial hypertension and elevated diastolic blood pressure are associated with a risk for AS requiring surgery in subjects below 60 years of age. Strict blood pressure control in this group is strongly advocated to avoid other cardiovascular diseases correlated to hypertension. If hypertension and elevated diastolic blood pressure are risk factors for developing AS requiring surgery need further investigations. Notably, elevated fasting glucose levels were related to AS requiring surgery in older adults without concomitant CAD.


Assuntos
Estenose da Valva Aórtica/etiologia , Pressão Arterial , Hipertensão/complicações , Adulto , Fatores Etários , Idoso , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Diástole , Feminino , Transtornos do Metabolismo de Glucose/complicações , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco
12.
JACC Heart Fail ; 7(3): 204-213, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30819375

RESUMO

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.

13.
Stroke ; 50(3): 610-617, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30786848

RESUMO

Background and Purpose- NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a risk factor for atrial fibrillation and a marker of cardiac function used in the detection of heart failure. Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke and to determine the predictive value beyond a panel of established risk factors. Methods- Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-Consortium, we analyzed data of 58 173 participants (50% men; mean age 52 y) free of stroke from 6 community-based cohorts. NT-proBNP measurements were performed in the central Biomarkers for Cardiovascular Risk Assessment in Europe laboratory. The outcomes considered were total stroke and subtypes of stroke (ischemic/hemorrhagic). Results- During a median follow-up time of 7.9 years, we observed 1550 stroke events (1176 ischemic). Increasing quarters of the NT-proBNP distribution were associated with increasing risk of stroke ( P for trend <0.0001; multivariable Cox regression analysis adjusted for risk factors and cardiac diseases). Individuals in the highest NT-proBNP quarter (NT-proBNP >82.2 pg/mL) had 2-fold (95% CI, 75%-151%) greater risk of stroke than individuals in the lowest quarter (NT-proBNP <20.4 pg/mL). The association remained unchanged when adjusted for interim coronary events during follow-up, and though it was somewhat heterogeneous across cohorts, it was highly homogenous according to cardiovascular risk profile or subtypes of stroke. The addition of NT-proBNP to a reference model increased the C-index discrimination measure by 0.006 ( P=0.0005), yielded a categorical net reclassification improvement of 2.0% in events and 1.4% in nonevents and an integrated discrimination improvement of 0.007. Conclusions- In European individuals free of stroke, levels of NT-proBNP are positively associated with risk of ischemic and hemorrhagic stroke, independently from several other risk factors and conditions. The addition of NT-proBNP to variables of established risk scores improves prediction of stroke, with a medium effect size.


Assuntos
Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Adulto , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Biomarcadores , Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento
14.
Ups J Med Sci ; 124(1): 21-28, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30618330

RESUMO

We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.


Assuntos
Sistema de Registros , Pesquisa Biomédica/métodos , Estudos de Coortes , Ética Médica , Estudos de Associação Genética , Humanos , Cooperação Internacional , Projetos Piloto , Modelos de Riscos Proporcionais , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/epidemiologia , Suécia/epidemiologia
15.
Clin Physiol Funct Imaging ; 39(2): 128-134, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30298591

RESUMO

AIMS: Non-invasive estimation of left ventricular filling pressure (LVFP) during stress is important for explaining exertional symptoms in patients with heart failure (HF). The aim of this study was to evaluate ability of Doppler echocardiographic measures of elevated LVFP with passive leg lifting (PLL) in patients with suspected HF. METHODS: Twenty-nine patients with clinical signs of HF who underwent simultaneous Doppler echocardiography and right heart catheterization (RHC) at rest and during PLL were consecutively investigated. Seventeen patients had normal PCWP (≤15 mmHg) at rest and during PLL and 12 with normal PCWP at rest but >15 mmHg with PLL. Conventional echo and 2D strain were used to assess early diastolic blood flow velocity (E), LV strain rate during early diastole (LVSRe), left atrial SR during atrial contraction (LASRa) and myocardial tissue Doppler velocities to assess lateral e' and further calculate E/e' and E/LVSRe and their relationship with PCWP, at rest and during PLL. RESULTS: Resting LAVI (ß = 0·45, P = 0·009) and LASRa (ß = -0·51, P = 0·004) were independently related to PCWP during PLL. Also, LASRa (ß = -0·77, P<0·001), E/e' (ß = 0·40, P = 0·04) and E/LVSRe (ß = 0·47, P = 0·021) during PLL correlated with PCWP during PLL. Multiple regression analysis identified E/LVSRe (ß = 0·46, P = 0·001) and LASRa (ß = -0·58, P = 0·002) during PLL as being independently associated with PCWP during PLL. CONCLUSION: Left atrial volume and myocardial contraction (LASRa) at rest both predict unstable LV filling pressures measured as raised PCWP when provoked by PLL. Furthermore, LASRa at PLL seems to have the strongest association to PCWP during PLL.


Assuntos
Cateterismo Cardíaco , Ecocardiografia Doppler , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Posicionamento do Paciente/métodos , Pressão Propulsora Pulmonar , Função Ventricular Esquerda , Pressão Ventricular , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
16.
Scand Cardiovasc J ; 52(6): 315-319, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30474426

RESUMO

OBJECTIVE: Increased levels of circulating endostatin have been observed in patients with prevalent ischemic heart disease. However, the association between circulating endostatin, and incident myocardial infarction (MI) is less studied. Our main aim was to study the association between circulating endostatin and incident MI in the community adjusted for established cardiovascular risk factors in men and women. DESIGN: Circulating endostatin was measured in a nested case control study based on three large community-based Swedish cohorts, including 533 MI cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with adjustments for established cardiovascular risk factors. RESULTS: Higher endostatin was associated with a higher incidence of MI independently of established cardiovascular risk factors (OR 1.19, 95% CI 1.03-1.37, p = .02), but this association was abolished after additional adjustment for C-reactive protein. Sex-stratified analyses suggest that the association was substantially stronger in women as compared to men. CONCLUSIONS: In our community based sample, higher endostatin predicted incident myocardial infarction predominantly in women but not independently of CRP. Thus, our findings do not support a broad utility of endostatin measurements for the prediction of incident myocardial infarction in clinical practice.


Assuntos
Endostatinas/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Prognóstico , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores Sexuais , Suécia/epidemiologia , Fatores de Tempo , Regulação para Cima
17.
Diab Vasc Dis Res ; 15(5): 387-395, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29992830

RESUMO

OBJECTIVE: To investigate the long-term prognostic value of insulin-like growth factor-binding protein 1 in patients with acute myocardial infarction. METHODS: Patients ( n = 180) with admission glucose < 11 mmol/L without previously known diabetes admitted for an acute myocardial infarction in 1998-2000 were followed for mortality and cardiovascular events (first of cardiovascular mortality/acute myocardial infarction/stroke/severe heart failure) until the end of 2011 (median 11.6 years). Fasting levels of insulin-like growth factor-binding protein 1 at day 2 were related to outcome in Cox proportional hazard regression analyses. RESULTS: Median age was 64 years, 69% were male and median insulin-like growth factor-binding protein 1 was 20 µg/L. Total mortality was 34% ( n = 61) and 44% ( n = 80) experienced a cardiovascular event during a median follow-up time of 11.6 years. After age adjustment, insulin-like growth factor-binding protein 1 was associated with all-cause (1.40; 1.02-1.93, p = 0.039) and cancer mortality (2.09; 1.15-3.79, p = 0.015) but not with cardiovascular death ( p = 0.29) or cardiovascular events ( p = 0.57). After adjustments also for previous myocardial infarction, previous heart failure and body mass index, insulin-like growth factor-binding protein 1 was still associated with all-cause mortality (1.38; 1.01-1.89, p = 0.046). CONCLUSION: In patients with acute myocardial infarction without previously known diabetes, high insulin-like growth factor-binding protein 1 was associated with long-term all-cause and cancer mortality but not with cardiovascular events.


Assuntos
Glicemia/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Infarto do Miocárdio/sangue , Idoso , Biomarcadores/sangue , Causas de Morte , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Neoplasias/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Regulação para Cima
18.
Artigo em Inglês | MEDLINE | ID: mdl-30004467

RESUMO

Information on the predictors of future hypertension in Mauritians with prehypertension is scant. The aim of this study was to analyze the 5-year and 11-year risk of hypertension and its predictors in people with normotension and prehypertension at baseline in Mauritius in 1987. This was a retrospective cohort study of 883 men and 1194 women of Mauritian Indian and Mauritian Creole ethnicity, aged 25⁻74 years old, free of hypertension at baseline in 1987 with follow-up examinations in 1992 and 1998 using the same methodology. The main outcome was 5- and 11-year risk of hypertension. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated. The 5-year risk of hypertension was 5.4-times higher in people with prehypertension compared with normotensive individuals at baseline. The corresponding odds for prehypertensive people at baseline regarding 11-year hypertension risk was 3.39 (95% CI 2.67⁻4.29) in the adjusted logistic regression models. Being of Creole ethnicity (OR 1.42; 95% CI 1.09⁻1.86) increased the 11-year odds of hypertension compared with the Indian population. It is of importance to screen for people with prehypertension and implement strategies to reduce their systolic blood pressure levels to the recommended levels of 120/80 mmHg. Special attention needs to be given to Mauritians of Creole ethnicity.


Assuntos
Pressão Sanguínea , Hipertensão/epidemiologia , Pré-Hipertensão/epidemiologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Modelos Logísticos , Masculino , Maurício/epidemiologia , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
19.
Eur J Prev Cardiol ; 25(16): 1765-1772, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29846119

RESUMO

Background The effect of primary prevention of cardiovascular disease is debated. The Västerbotten Intervention Programme (VIP) is an individual and community-based public health programme that comprises the whole county of Västerbotten (VB). In the neighbouring county of Norrbotten (NB), no programmes have been implemented. Method Between 1994 and 2014, five surveys were performed in the two counties on persons aged 40 to 75 years within the Northern Sweden MONICA Study. The number of subjects participating was 6600 (75.4%). We compared time trends in risk factors between the two counties using regression models including age, county and year of survey. To test whether time trends differed between counties, the interaction between county and year was included in the models. Results Systolic blood pressure declined in both counties, and the decline was faster in Västerbotten than in Norrbotten ( p = 0.043 for interaction county*year). Diastolic blood pressure declined in VB but increased in NB ( p < 0.001). Cholesterol levels declined at a similar rate in both counties whereas body mass index increased in both counties. Fasting glucose decreased in VB ( p = 0.003) and increased in NB. The prevalence of regular smokers decreased faster in VB than in NB ( p = 0.01). Trend in waist and hip circumference, known diabetes, having an academic degree, being physically inactive or 10 year cardiovascular mortality according to SCORE did not differ. Conclusion Blood pressure, glucose and smoking improved at a faster rate in the county with a community and primary care-based intervention than in the county without such an intervention.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Serviços de Saúde Comunitária/tendências , Atenção Primária à Saúde/tendências , Prevenção Primária/tendências , Adiposidade , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Feminino , Nível de Saúde , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Proteção , Medição de Risco , Fatores de Risco , Abandono do Hábito de Fumar , Suécia/epidemiologia , Fatores de Tempo
20.
Circulation ; 138(6): 590-599, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29487139

RESUMO

BACKGROUND: Aortic valve stenosis (AS) is the most common indication for cardiac valve surgery; untreated AS is linked to high mortality. The etiological background of AS is unknown. Previous human studies were typically based on case-control studies. Biomarkers identified in prospective studies could lead to novel mechanistic insights. METHODS: Within a large population survey with blood samples obtained at baseline, 334 patients were identified who later underwent surgery for AS (median age [interquartile range], 59.9 [10.4] years at survey and 68.3 [12.7] at surgery; 48% female). For each case, 2 matched referents were allocated. Plasma was analyzed with the multiplex proximity extension assay for screening of 92 cardiovascular candidate proteins. Conditional logistic regression models were used to assess associations between each protein and AS, with correction for multiple testing. A separate set of 106 additional cases with 212 matched referents was used in a validation study. RESULTS: Six proteins (growth differentiation factor 15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9) were associated with case status in the discovery cohort; odds ratios ranged from 1.25 to 1.37 per SD increase in the protein signal. Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Subanalyses of case-referent triplets (n=133) who showed no visible coronary artery disease at the time of surgery in the index person supported associations between AS and growth differentiation factor 15 (odds ratio, 1.40; 95% confidence interval, 1.10-1.78) and galectin-4 (odds ratio, 1.27; 95% confidence interval, 1.02-1.59), but these associations were attenuated after excluding individuals who donated blood samples within 5 years before surgery. In triplets (n=201), which included index individuals with concurrent coronary artery disease at the time of surgery, all 6 proteins were robustly associated with case status in all sensitivity analyses. In the validation study, the association of all but 1 (interleukin 17 receptor A) of these proteins were replicated in patients with AS with concurrent coronary artery disease but not in patients with AS without coronary artery disease. CONCLUSIONS: We provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.


Assuntos
Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/cirurgia , Proteínas Sanguíneas/análise , Implante de Prótese de Valva Cardíaca , Proteômica/métodos , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/sangue , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/epidemiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Comorbidade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Feminino , Galectina 4/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Pró-Proteína Convertase 9/sangue , Estudos Prospectivos , Receptores de Interleucina-17/sangue , Receptores da Transferrina/sangue , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Suécia/epidemiologia , Fator de von Willebrand/análise
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