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1.
Circulation ; 140(22): 1834-1850, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31765261

RESUMO

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.

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.
Sci Rep ; 9(1): 16208, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700048

RESUMO

Red Cell Distribution Width (RDW) could be a risk factor for developing various chronic diseases, and seems to be a prognostic marker in patients with cardiovascular disease (CVD) or cancer. Our aim was to explore the association between RDW and all-cause and cause-specific mortality in a general population. RDW was measured in 27,063 participants (aged 45-73 years) from the population-based Malmö Diet and Cancer cohort. After a follow-up of 19.8 ± 5.5 years, Cox proportional hazards regression analysis was used to study the relationship between RDW and all-cause and cause-specific mortality, with adjustment for confounding factors. A total of 9388 individuals (4715 men and 4673 women) died during the follow up. High RDW was significantly associated with all-cause mortality (HR, 4th vs. 1st quartile: 1.34, 95%CI: 1.24-1.45), cancer mortality (HR: 1.27, 95%CI: 1.12-1.44), CVD mortality (HR: 1.39, 95%CI: 1.21-1.59), and respiratory disease mortality (HR: 1.47, 95%CI: 1.06-2.03). The C-statistic increased significantly from 0.732 to 0.737 when adding RDW to a model adjusted for age and sex. There was a significant interaction between RDW and BMI with respect to all-cause mortality. We concluded that RDW is associated with mortality and propose that high RDW is a significant, but non-specific marker of mortality risk in the general population.

4.
Ann Neurol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31721283

RESUMO

OBJECTIVE: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies. METHODS: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991-1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), ß-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009-2015). RESULTS: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03-1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10-1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77-1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07-3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05-2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87-1.90] for Aß42 and 1.35 [95% CI = 0.86-2.13] for Aß42 /p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies. INTERPRETATION: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2019.

5.
Environ Res ; 180: 108826, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31654906

RESUMO

BACKGROUND: Cadmium is a toxic metal and exposure is mainly from diet and tobacco smoke. Cadmium is accumulated in blood vessels and may reduce synthesis of procollagen and inhibit proliferation of vascular smooth muscle cells. High blood cadmium has been associated with increased risk of myocardial infarction, stroke and unruptured intracranial aneurysms. We examined whether blood cadmium increase the risk of subarachnoid haemorrhage (SAH). METHODS: The Malmö Diet and Cancer cohort (n = 28,449) was examined in 1991-1996 and blood samples were taken. Incidence of SAH was followed up to 2014. Cadmium was measured in stored blood samples from incident SAH cases and matched controls (n = 93 vs n = 276) and odds ratio (OR) for SAH was assessed in a nested case control design. RESULTS: Subjects with cadmium concentration in the highest quartile had increased risk of SAH compared to those in the first quartile (OR: 3.22, 95%CI: 1.67-6.22). However, after adjusting for smoking, results were weakened and non-significant (OR: 1.57, 95%CI: 0.51-4.80). CONCLUSIONS: Cadmium concentration was associated with increased risk of SAH but this association was largely explained by smoking. Whether cadmium in tobacco may contribute to the vascular pathology and increased risk of SAH in smokers should be further studied.

6.
Circ Res ; 125(8): 773-782, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31476962

RESUMO

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.

7.
Int J Epidemiol ; 2019 Jul 30.
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.
Heart ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405897

RESUMO

BACKGROUND: Low resting heart rate and premature atrial contractions (PACs) predict incident atrial fibrillation (AF) and could be interdependent, since PACs occur in the gaps between normal beats. OBJECTIVE: To study the association between low heart rate at 24hECG, PACs and incident AF in a prospective population-based cohort. METHODS: In the Malmö Diet and Cancer study, 24hECGs were performed in 377 AF-free subjects. The endpoint was clinical AF retrieved from national hospital (mean follow-up 17 years). The interaction between increased supraventricular activity (SVA) top quartile of either PACs/hour or supraventricular tachycardias/hour) and mean heart rate (mHR) as regards AF risk was assessed in multivariable Cox regression analyses adjusted for age, sex, height, BMI, systolic blood pressure, antihypertensive medication, smoking and homeostasis model assessment of insulin resistance. RESULTS: There were 80 (21%) incident cases of AF. Below median mHR (80 bpm/75 bpm for women/men) was associated with increased AF incidence (HR: 1.89, 95% CI 1.18 to 3.02, p=0.008). There was no correlation between mHR and SVA (p=0.6) or evidence of a multiplicative interaction between these factors for AF risk (p for interaction=0.6) In the group with both increased SVA and below median mHR (17% of the population) the relative risk of AF was very high (HR 4.5, 95% CI 2.2 to 9.1, p=0.001). CONCLUSION: Low mHR at 24hECG independently predicts AF, but there is no association between mHR and SVA, and these factors are independent as regards AF risk. Subjects with both low mHR and increased SVA have high AF risk.

9.
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.

10.
Thromb Haemost ; 119(11): 1773-1784, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31430798

RESUMO

Studies evaluating the relationship between platelet indices and cardiovascular (CV) outcomes yielded conflicting results. We assessed the incidence of adverse events according to baseline quintiles of platelet indices in the prospective cohort of the Malmö Diet and Cancer Study. A total of 30,314 individuals (age 57 ± 8 years) were followed for a median of 16 years (468,490 person-years). Outcome measures included all-cause death, CV death, myocardial infarction (MI), and ischemic stroke. The fifth quintile of platelet count (> 274.6 × 109/L) was associated with higher incidence of all-cause death (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.32, p < 0.001), CV death (HR 1.19, 95% CI 1.00-1.42; p = 0.044), MI (HR 1.32, 95% CI 1.12-1.54; p = 0.001), and ischemic stroke (HR 1.27, 95% CI 1.08-1.50, p = 0.004) compared with the first quintile (≤ 185 × 109/L), and also associated with a lower survival, regardless of previous history of MI (p for interaction = 0.58) or stroke (p for interaction = 0.42). In the highest quintile, history of stroke had a higher risk of CV death (HR 3.18, 95% CI 1.54-6.54) compared with no previous stroke (HR 1.12, 95% CI 0.96-1.31). The risk of MI and stroke was greatest in the fifth quintile, regardless of previous MI or previous stroke, respectively. The risk of all adverse events was similar across different quintiles of mean platelet volume. In conclusion, elevated platelet count is associated with higher mortality and risk of CV events, regardless of previous MI and stroke. Platelet count may thus be a useful marker for further stratification of CV risk, and especially of death.

11.
Eur J Prev Cardiol ; 26(18): 1987-1997, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31409109

RESUMO

AIMS: The CHA2DS2VASc score is used to evaluate the risk of thromboembolic events in patients with non-valvular atrial fibrillation. We assessed the prognostic yield of CHA2DS2VASc for new-onset atrial fibrillation, cardiovascular morbidity and mortality in a non-atrial fibrillation population. METHODS: We analysed a population-based cohort of 22,179 middle-aged individuals with (n = 3542) and without (n = 18,367) a history of atrial fibrillation; we grouped the population into five CHA2DS2VASc strata (0-1-2-3-≥4), and compared the risk of major adverse cerebro-cardiovascular events and mortality. Furthermore, we analysed the annual incidence of atrial fibrillation across different CHA2DS2VASc strata. RESULTS: Over a median follow-up of 15 years, 1572 patients (6.9%) had ischaemic strokes, 2162 (9.5%) coronary events and 5899 (26%) died. The cumulative incidence of ischaemic stroke in CHA2DS2VASc ≥ 4 subjects without atrial fibrillation was similar to patients with atrial fibrillation and CHA2DS2VASc 2, with a 10-year crude incidence rate of 0.91 (95% confidence interval (CI) 0.68-1.19) and 1.13 (95% CI 0.93-1.36) ischaemic strokes per 100 patient-years, respectively. CHA2DS2VASc in a non-atrial fibrillation population showed higher predictive accuracy for ischaemic stroke compared with an atrial fibrillation population (area under the curve 0.60 vs. 0.56; P = 0.001). In multivariable Cox regression analysis, CHA2DS2VASc ≥ 2 was an independent predictor of all-cause death (adjusted hazard ratio (aHR) 2.58; 95% CI 2.42-2.76), cardiovascular death (aHR 3.40; 95% CI 2.98-3.89), ischaemic stroke (aHR 2.20; 95% CI 1.92-2.53) and coronary events (aHR 1.83; 95% CI 1.63-2.04). The cumulative incidence of atrial fibrillation was greater with increasing CHA2DS2VASc strata, with an absolute annual incidence of more than 2% per year if CHA2DS2VASc ≥ 4. CONCLUSION: The CHA2DS2VASc score is a sensitive tool for predicting new-onset atrial fibrillation and adverse outcomes in subjects both with and without atrial fibrillation.

12.
Stroke ; 50(8): 1989-1996, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31272321

RESUMO

Background and Purpose- Cellular apoptosis is an important feature in atherosclerosis, contributing to necrotic core formation, and plaque vulnerability. Activation of the death receptor TRAIL-R2 (TNF [tumor necrosis factor]-related apoptosis-inducing ligand receptor 2) through its ligand tumor necrosis factor-relate apoptosis-inducing ligand (TRAIL), induces apoptosis in cells in vitro. sTRAIL-R2 (soluble TRAIL-R2) was recently shown to predict cardiovascular events in healthy individuals. In the present study, we explored if plaque levels of sTRAIL-R2 and sTRAIL reflect plaque apoptosis and vulnerability and if plasma levels of these markers predict future events in subjects with advanced atherosclerosis. Methods- Plasma from 558 patients and 202 carotid plaques from the Carotid Plaque Imaging Project biobank were used. sTRAIL-R2, sTRAIL, and caspase-8 levels were assessed using a Proseek Multiplex CVD96×96 assay. Active caspase-3 was measured using ELISA to assess plaque apoptosis. Plaque morphology was studied by immunohistochemistry. Inflammatory cytokines were assessed by Luminex. mRNA levels were quantified by RNA sequencing. Monocytes, T cells, B cells, and human coronary artery smooth muscle cells were used to study sTRAIL-R2 and sTRAIL release on cell apoptosis and inflammatory stimuli in vitro. Results- Plaque levels of sTRAIL-R2 and sTRAIL correlated to markers of extrinsic induced apoptosis (caspase-3 and -8). sTRAIL-R2 and sTRAIL protein expression were increased in symptomatic carotid plaques and patients with higher plasma levels of sTRAIL-R2 had a higher risk of future cardiovascular events. sTRAIL-R2 and sTRAIL were released upon activation of the extrinsic apoptosis pathway in vitro. sTRAIL-R2 and sTRAIL correlated with inflammatory cytokines, to CD68 expression and inversely to α-actin in the plaque tissue. Conclusions- The present study shows that sTRAIL-R2 and sTRAIL are associated to human plaque cell apoptosis, plaque inflammatory activity, and with symptomatic carotid plaques. Furthermore, high plasma levels of sTRAIL-R2 in plasma predict, independently, future cardiovascular events in individuals with manifest atherosclerotic disease.

13.
Biomarkers ; 24(6): 615-621, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31215249

RESUMO

Purpose: The aim of this study is to evaluate plasma biomarkers as predictors for peripheral arterial disease (PAD). Materials and methods: Prospective longitudinal cohort study of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (MDCS) (n = 5550; 1991-94). Cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional proatrial natriuretic peptide (MR-proANP), mid-regional proadrenomedullin (MR-proADM), and conventional risk factors were measured at baseline. The diagnosis of symptomatic PAD was validated in 97% of the cases. Results: Cumulative incidence of PAD during median follow up of 23.4 years was 4.4% (men 5.9%, women 3.3%). Adjusted for age, sex, smoking, body mass index, hypertension, diabetes mellitus and total cholesterol, copeptin (hazard ratio [HR] 1.46; 95% confidence interval [CI] 1.19-1.80), N-BNP (HR 1.28; 95% CI 1.11-1.48), and cystatin C (HR 1.19; 95% CI 1.10-1.29) were independently associated with incident PAD. Subjects with the three biomarkers copeptin, N-BNP, and cystatin C in the highest quartiles, ran a high risk of incident PAD (HR 3.29; 95% CI 1.76-6.17) compared to those with no biomarker in the highest quartile. Conclusion: Copeptin, N-BNP, and cystatin C were associated with incident symptomatic PAD, implying that these biomarkers are sensitive indicators of early subclinical PAD. Clinical significance First prospective longitudinal cohort study evaluating Cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional proatrial natriuretic peptide (MR-proANP), and mid-regional proadrenomedullin (MR-proADM) as predictors for peripheral arterial disease (PAD). Copeptin, N-BNP, and Cystatin C where independently associated with incident symptomatic PAD after adjustment for conventional risk factors. Copeptin, N-BNP, and Cystatin C seem to be sensitive indicators of early subclinical PAD.

14.
Diabetes Care ; 42(8): 1582-1588, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201260

RESUMO

OBJECTIVE: HER2/ErbB2 is a member of the epidermal growth factor receptor family. It is widely used as a tumor marker, but it also has recently been associated with insulin resistance. Both ErbB2 and diabetes have been associated with cancer; however, the relationship between ErbB2 and diabetes has not been well explored. The aim of this population-based cohort study was to assess the association between plasma ErbB2 and incidence of diabetes. RESEARCH DESIGN AND METHODS: The study population included participants from the Malmö Diet and Cancer-Cardiovascular Cohort (age range 46-68 years). After excluding participants with a history of diabetes and those missing data for ErbB2 and other covariates, the final study population consisted of 4,220 individuals. Incidence of diabetes was followed through linkages to local and national registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to quartiles of ErbB2, adjusted for potential confounders. RESULTS: Plasma ErbB2 was significantly and positively associated with glucose, insulin, and HbA1c after being adjusted for potential confounding factors. During a mean ± SD follow-up period of 20.20 ± 5.90 years, 615 participants (14.6%) were diagnosed with new-onset diabetes. Individuals with high levels of ErbB2 had a significantly higher risk of diabetes than those with low levels of ErbB2. The multivariable-adjusted hazard ratio was 1.31 (95% CI 1.03-1.66; P < 0.05) for the highest versus the lowest quartile of ErbB2 and was 1.15 (95% CI 1.05-1.25; P < 0.05) per 1-SD increase in ErbB2. CONCLUSIONS: Elevated levels of ErbB2 are associated with increased incidence of diabetes.

15.
Environ Health ; 18(1): 56, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200698

RESUMO

BACKGROUND: Smoking is a strong risk factor for cardiovascular disease (CVD) and causes exposure to cadmium, which is a pro-atherosclerotic metal. Cadmium exposure has also been shown to increase the risk of CVD, even after adjustment for smoking. Our hypothesis was that part of the risk of CVD in smokers may be mediated by cadmium exposure from tobacco smoke. We examined this hypothesis in a mediation analysis, trying to assess how much of the smoking-induced CVD risk could be explained via cadmium. METHODS: We used prospective data on CVD (incidence and mortality) in a Swedish population-based cohort of 4304 middle-aged men and women (the Malmö Diet and Cancer Study). Blood cadmium was analyzed in base-line samples from 1991, and clinical events were followed up for 16-19 years based on registry data. Mediation analysis was conducted to evaluate the indirect effect (via cadmium) of smoking on CVD. Survival was analyzed by the accelerated failure time (AFT) model and the Aalen additive hazard model. RESULTS: The mean blood cadmium level in the study population was 0.43 µg/L (median 0.24 µg/L) and increased with recent and current smoking. As expected, shorter survival time (AFT model) and higher incidence rate (Aalen model) were found in current smokers for all CVD outcomes and this effect seemed to be partly mediated by cadmium. For the sum of acute myocardial infarction, bypass grafts and percutaneous coronary intervention, and death in ischemic heart disease, about half of the increased risk of such events in current smokers was mediated via cadmium, with similar results for the AFT and Aalen models. CONCLUSIONS: Cadmium plays an important role in smoking-induced CVDs. This provides evidence for mechanisms and is of importance for both individuals and policy makers.

16.
Angiology ; 70(10): 929-937, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31234636

RESUMO

The morphology and function of the arteries can be directly measured using different established methods. This prospective cohort study aimed to translate 2 of these, aortic pulse wave velocity (aPWV) and carotid intima-media thickness (cIMT), into a combined Vascular Aging Index (VAI) and then evaluate the predictive power of aPWV, cIMT, and VAI. Patients (n = 2718) were included from the cardiovascular arm of the Malmö Diet and Cancer Study (median age 71.9 years, 62.2% females). Total follow-up time was 16 448 person-years and a composite cardiovascular disease (CVD) end point was used. Cox regressions yielded adjusted hazard ratios (95% confidence interval) per 1 standard deviation increment of loge aPWV, loge cIMT, and loge VAI of 1.25 (1.08-1.45, P = .003), 1.27 (1.13-1.44, P < .001), and 1.45 (1.26-1.68, P < .001), respectively. The C-statistics increased from 0.714 to 0.734 when adding aPWV and cIMT to a model of conventional risk factors. Net Reclassification Index also showed a significant (P < .001) improvement for the classification of event-free patients and no change for patients with events. A VAI based on aPWV and cIMT had a good predictive performance. Used together, aPWV and cIMT incrementally and significantly improve the prediction of CVD events by correctly down-adjusting the predicted risk for noncases.


Assuntos
Envelhecimento , Aorta/fisiopatologia , Doenças Cardiovasculares/mortalidade , Espessura Intima-Media Carotídea/mortalidade , Idoso , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Onda de Pulso/métodos , Fatores de Risco , População Urbana/estatística & dados numéricos
17.
Diab Vasc Dis Res ; 16(5): 466-473, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31064217

RESUMO

BACKGROUND: Advanced glycation end product is an established risk marker in diabetic vascular disease, but its possible associations with atherosclerosis in a general population are yet to be investigated. We studied the degree of carotid atherosclerosis and its association with skin autofluorescence in an elderly population. METHODS: Carotid ultrasound and skin autofluorescence measurements were performed in a subpopulation within the 'Malmö Diet and Cancer Cardiovascular Cohort' re-examination study (n = 523). Total plaque area including all prevalent plaques in the right carotid artery was calculated. Complete data on all variables were available for 496 subjects (mean age 72 years). RESULTS: Each 1 standard deviation increment of skin autofluorescence was associated with increased risk of prevalent large plaques (odds ratio, 1.32; 95% confidence interval, 1.05-1.66; p = 0.018) independently of diabetes and cardiovascular risk factors. The top versus bottom tertile of the skin autofluorescence was associated with an approximately twofold risk of being in the population with the highest plaque burden [top quartile with total plaque area ⩾ 35 mm2 (odds ratio, 1.88; 95% confidence interval, 1.05-3.39; p for trend = 0.027)] in fully adjusted analysis. CONCLUSION: In an elderly population, skin autofluorescence was associated with increasing degree of carotid atherosclerosis measured as total plaque area, independently of diabetes and cardiovascular risk factors.

18.
Sci Rep ; 9(1): 5609, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30948779

RESUMO

Long follow up is needed in prospective cohort study evaluation of plasma biomarkers for incident peripheral arterial disease (PAD) Middle-aged PAD-free individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (n = 5550; 1991-94) were followed prospectively for a median time of 23.4 years. The plasma biomarkers lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and mass, proneurotensin, and CRP, were studied in relation to incidence of PAD until December 31st, 2016. The diagnosis of PAD could be validated and confirmed in 98%. Cox regression was used to calculate hazard ratios (HR) per 1 standard deviation increment of each respective log transformed plasma biomarker. Cumulative incidence of PAD was 4.4% (men 5.9%, women 3.3%). Adjusting for age, gender, smoking, body mass index, hypertension, diabetes mellitus, Lp-PLA2 activity (HR 1.33; 95% CI 1.17-1.52), Lp-PLA2 mass (HR 1.20; 95% CI 1.05-1.37) and CRP (HR 1.55; 95% CI 1.36-1.76) remained independently associated with incident PAD. The plasma biomarkers Lp-PLA2 activity and mass, and CRP were markers of PAD risk, implying that they might be useful biomarkers for subclinical atherosclerosis and atherosclerotic disease.

19.
PLoS One ; 14(3): e0214083, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30883602

RESUMO

BACKGROUND: Breathlessness is prevalent in the general population and may be associated with adverse health outcomes. This study aimed to evaluate the association of breathlessness with Chronic Obstructive Pulmonary Disease (COPD) events, cardiac events and all-cause mortality from middle-age throughout life. METHODS: Breathlessness was measured in 699, 55-year old men residing in Malmö, Sweden using modified Medical Research Council (mMRC). COPD events (hospitalisation, death or diagnosis) cardiac events and all-cause mortality was assessed using The Swedish Causes of Death Register and Hospital Discharge Register. Data was analyzed using Cox- and competing risks (Fine-Gray) regression analysis. RESULTS: 695 (99%) of 699 participants died and four emigrated during follow up. Eighty-seven (12%) had mMRC = 1 and 19 (3%) had mMRC≥2. Breathlessness was associated with COPD events; adjusted Sub-Hazard Ratio 2.1 (95% CI, 1.2-3.6) for mMRC = 1 and 7.5 (2.6-21.7) for mMRC ≥ 2 but not associated with cardiac events when adjusting for competing events and confounding. Breathlessness was associated increased all- cause mortality (Hazard Ratios of 1.4 (1.1-1.7) (mMRC = 1) and 3.4 (2.1-5.6) (mMRC ≥ 2)). CONCLUSION: Breathlessness is associated with increased risk of COPD events and increase in all-cause mortality from age 55 until death.

20.
Arterioscler Thromb Vasc Biol ; 39(5): 925-933, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30917679

RESUMO

Objective- RAGE (receptor for advanced glycation end products) and EMMPRIN (extracellular matrix metalloproteinase inducer) are immune receptors for proinflammatory mediators. These receptors can also be found in a soluble form in the circulation. Soluble RAGE (sRAGE) has shown atheroprotective properties in animal studies, possibly by acting as a decoy receptor for its ligands. Whether sEMMPRIN (soluble EMMPRIN) has similar roles is unknown. We hypothesized that sRAGE and sEMMPRIN might be associated with vascular disease progression, incident coronary events, and mortality. Approach and Results- We measured baseline sRAGE and sEMMPRIN in 4612 cardiovascular disease-free individuals from the population-based Malmö Diet and Cancer cohort. Measurements of intima-media thickness in the common carotid artery were performed at inclusion and after a median of 16.5 years. sRAGE was negatively correlated with carotid intima-media thickness progression, independently of traditional cardiovascular risk factors, kidney function, and hsCRP (high sensitive C-reactive protein). Additionally, sRAGE was associated with decreased risk for major adverse coronary events (hazard ratio=0.90 [0.82-0.97]; P=0.009) and mortality (hazard ratio=0.93 [0.88-0.99]; P=0.011) during a follow-up period of 21 years. The relationship with mortality was independent of all considered potential confounders. We found no correlations between EMMPRIN, intima-media thickness progression, or prognosis. Conclusions- Individuals with high levels of circulating sRAGE have a slower rate of carotid artery disease progression and a better prognosis. Although its predictive value was too weak to promote sRAGE as a useful clinical biomarker in the population, the findings support further research into the potential anti-inflammatory and atheroprotective properties of this soluble receptor.

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