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1.
Circ Res ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31476962

RESUMO

RATIONALE: Pro-inflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of monocyte-chemoattractant protein-1 (MCP-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 METHODS AND RESULTS: We used previously unpublished data on 17,180 stroke-free individuals (mean age 56.7{plus minus}8.1 years; 48.8% males) from six population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke over a mean follow-up interval of 16.3 years (280,522 person-years at risk; 1,435 incident stroke events). We applied Cox proportional hazard models and pooled hazard ratios (HR) using random-effects meta-analyses. Following 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 to the 1st quartile (HRs: 2nd quartile: 1.19 [1.00-1.42]; 3rd quartile: 1.35, [1.14-1.59]; 4th quartile: 1.38, [1.07-1.77]). There was no indication for heterogeneity across studies and in a sub-sample of four studies (12,516 individuals) the risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity 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.

2.
Endocr Connect ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505464

RESUMO

OBJECTIVE: Metabolic syndrome and obesity are risk factors for chronic kidney disease. However, early kidney alterations may escape diagnosis in these conditions due to glomerular hyperfiltration. Uromodulin, a glycoprotein exclusively synthesized in tubular cells of the thick ascending limb of Henle's loop, is a novel tissue-specific biomarker for kidney function. In contrast to the commonly used markers creatinine and cystatin C, serum uromodulin does not primarily depend on glomerular filtration. We hypothesized that serum uromodulin is a marker for metabolic syndrome and related components. DESIGN: The analyses included 1088 participants of the population-based KORA F4 study aged 62-81 years. Metabolic syndrome was present in 554 participants. After a mean follow-up time of 6.5 years, 621 participants were reevaluated, of which 92 had developed incident metabolic syndrome. METHODS: The association of serum uromodulin with metabolic syndrome and its components were assessed using multivariable logistic regression models. RESULTS: Serum uromodulin was inversely associated with metabolic syndrome after adjustment for sex, age, estimated glomerular filtration rate, physical activity, smoking, alcohol consumption and high sensitivity C-reactive protein (OR 0.65; 95% CI 0.56-0.76 per standard deviation uromodulin; p<0.001). Serum uromodulin was inversely associated with all single components of metabolic syndrome. However, serum uromodulin was not associated with new-onset metabolic syndrome after the follow-up period of 6.5 ± 0.3 years (OR 1.18; 95% CI 0.86-1.60). CONCLUSIONS: Serum uromodulin is independently associated with prevalent, but not with incident metabolic syndrome. Low serum uromodulin may indicate a decreased renal reserve in the metabolic syndrome.

3.
Nutrients ; 11(8)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412610

RESUMO

The objective of the study was to investigate the potential association of human milk leptin concentrations with child body mass index (BMI) and BMI trajectory patterns up to two years of age among children in the Ulm SPATZ Health Study. Leptin concentration was measured in skimmed human milk by ELISA (R&D System). Child BMI was determined at two to three days, three to four weeks, four to five months, one year, and two years of age. In SPATZ, leptin concentration at six weeks was inversely associated with child BMI at four to five weeks [beta -0.13, 95%CI -0.21;-0.05)] and at three to four months -0.12 -0.21;-0.03)]. Among infants of average BMI shortly after delivery, six week leptin was positively associated with greater increase in BMI from four to five weeks up to two years of age [0.16 (0.04;0.27)]. No associations were observed for six month leptin. Direction of association was the same in the Ulm Birth Cohort Study (UBCS), but statistically insignificant as the point estimate included the null effect value. Our results from SPATZ suggest human milk leptin may play a role in early infant growth. However, it is plausible that the lack of associations in UBCS suggest that these differences of human milk leptin composition between populations could have an impact in infant growth and development in a given population.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31375970

RESUMO

PURPOSE: To investigate the associations of diuretics overall, non-potassium-sparing diuretics in specific, and laxative use with cardiovascular mortality (CVM) in subjects with antihypertensive treatment. METHODS: Analyses included 4253 participants, aged 50 to 75 years, from the German ESTHER cohort and 105,359 participants, aged 50 to 69 years, from the UK Biobank. Cox proportional hazard regression models were applied in both studies, and then results were pooled using random-effects model meta-analyses. RESULTS: During 14 and 7 years of follow-up, 476 and 1616 CVM cases were observed in the ESTHER study and the UK Biobank, respectively. Compared to non-users, a 1.6-fold (hazard ratio [95% confidence interval] 1.57 [1.29; 1.90]), a 1.4-fold (1.39 [1.26; 1.53]), and no statistically significantly increased (1.13 [0.94; 1.36]) CVM were observed in users of diuretics overall, non-potassium-sparing diuretics in specific, and laxatives, respectively. Concurrent use of non-potassium-sparing diuretics and laxatives was associated with a 2-fold increased CVM (2.05 [1.55; 2.71]) when compared to users of neither diuretics nor laxatives. However, a test for interaction slightly missed statistical significance (p = 0.075). CONCLUSIONS: These consistent results from two large cohort studies imply that more research is needed on the safety of diuretics in routine care. Although not statistically significant in this study, a drug-drug interaction of non-potassium-sparing diuretics and laxatives appears plausible. Physicians and pharmacists are advised to clarify additional laxative use in users of non-potassium-sparing diuretics and inform about the risk of concurrent use. Moreover, closer potassium monitoring intervals (e.g., every 3 months) might be indicated in concurrent users to prevent fatal cardiovascular events.

6.
J Am Heart Assoc ; 8(15): e010881, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31311438

RESUMO

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

7.
Eur Heart J ; 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31209498

RESUMO

AIMS: Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with atherosclerotic coronary heart disease in three independent cohort studies. METHODS AND RESULTS: Ceramides and PCs were analysed using liquid chromatography-mass spectrometry (LC-MS) in three studies: WECAC (The Western Norway Coronary Angiography Cohort) (N = 3789), LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) trial (N = 5991), and KAROLA (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung) (N = 1023). A simple risk score, based on the ceramides and PCs showing the best prognostic features, was developed in the WECAC study and validated in the two other cohorts. This score was highly significant in predicting CVD mortality [multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.44 (1.28-1.63) in WECAC, 1.47 (1.34-1.61) in the LIPID trial, and 1.69 (1.31-2.17) in KAROLA]. In addition, a combination of the risk score with high-sensitivity troponin T increased the HRs to 1.63 (1.44-1.85) and 2.04 (1.57-2.64) in WECAC and KAROLA cohorts, respectively. The C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. The ceramide-phospholipid risk score showed comparable and synergistic predictive performance with previously published CVD risk models for secondary prevention. CONCLUSION: A simple ceramide- and phospholipid-based risk score can efficiently predict residual CVD event risk in patients with coronary artery disease.

8.
Cardiovasc Diabetol ; 18(1): 71, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164165

RESUMO

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

9.
J Am Heart Assoc ; 8(12): e011882, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31189389

RESUMO

Background High-sensitivity cardiac troponins T and I (hs- cTnT and hs- cTnI ) are established biomarkers for myocardial injury and used for diagnostic and prognostic purposes. However, whether repeat measurements improve prediction of recurrent cardiovascular disease ( CVD ) events in patients with stable coronary heart disease ( CHD ) after adjustment for several other novel biomarkers remains unclear. Methods and Results We measured both troponins in 873 coronary heart disease patients from the KAROLA (Langzeiterfolge der Kardiologischen Anschlussheilbehandlung) study about 9 weeks after their initial acute event (baseline) and after 12 months, followed them for 12 years, assessed a combined CVD end point, and adjusted for several risk factors. As we found evidence for effect modification, results were stratified according to presence of myocardial infarction at baseline. During follow-up, 186 fatal and non-fatal CVD events occurred. Both baseline and 12-months troponin concentrations were significantly associated with CVD events in patients without myocardial infarction at baseline; in tendency 12 months of troponin showed stronger hazard ratios (hs- cTnT : hazard ratios 1.91 (95% CI 1.17-3.11) versus baseline values 1.71 (95% CI 1.08-2.70) and for hs- cTnI : hazard ratio 1.55 (95% CI 1.05-2.30) versus baseline value 1.22 (95% CI 0.88-1.68) in the fully and simultaneously adjusted model. Conclusions Both troponins are consistently associated with recurrent cardiovascular events after adjustment for emerging risk factors during follow-up in our study especially evident in patients without myocardial infarction at baseline. Troponin values at 12 months of follow-up showed independent associations with future CVD events in addition to baseline assessments of troponins.

10.
Eur J Nutr ; 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31089867

RESUMO

PURPOSE: Inter-individual metabolic differences may be a reason for previously inconsistent results in diet-diabetes associations. We aimed to investigate associations between dietary intake and diabetes for metabolically homogeneous subgroups ('metabotypes') in a large cross-sectional study. METHODS: We used data of 1517 adults aged 38-87 years from the German population-based KORA FF4 study (2013/2014). Dietary intake was estimated based on the combination of a food frequency questionnaire and multiple 24-h food lists. Glucose tolerance status was classified based on an oral glucose tolerance test in participants without a previous diabetes diagnosis using American Diabetes Association criteria. Logistic regression was applied to examine the associations between dietary intake and diabetes for two distinct metabotypes, which were identified based on 16 biochemical and anthropometric parameters. RESULTS: A low intake of fruits and a high intake of total meat, processed meat and sugar-sweetened beverages (SSB) were significantly associated with diabetes in the total study population. Stratified by metabotype, associations with diabetes remained significant for intake of total meat (OR 1.67, 95% CI 1.04-2.67) and processed meat (OR 2.23, 95% CI 1.24-4.04) in the metabotypes with rather favorable metabolic characteristics, and for intake of fruits (OR 0.83, 95% CI 0.68-0.99) and SSB (OR:1.21, 95% CI 1.09-1.35) in the more unfavorable metabotype. However, only the association between SSB intake and diabetes differed significantly by metabotype (p value for interaction = 0.01). CONCLUSIONS: Our findings suggest an influence of metabolic characteristics on diet-diabetes associations, which may help to explain inconsistent previous results. The causality of the observed associations needs to be confirmed in prospective and intervention studies.

11.
Calcif Tissue Int ; 105(2): 173-182, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31069442

RESUMO

Effects of low serum 25OHD on age-related changes in muscle mass and function remain unclear. Our aims were to explore associations of baseline 25OHD levels with prevalent and incident sarcopenia and changes in muscle parameters, and to examine the role of parathyroid hormone (PTH) therein. Cross-sectional (n = 975) and prospective analyses (n = 702) of older adults aged 65-93 years participating in the KORA-Age study. Sarcopenia was defined using the 2010 European Working Group on Sarcopenia in Older People (EWGSOP) criteria as low muscle mass combined with low grip strength or low physical performance. Associations with baseline 25OHD were examined in multiple regression analyses. Low vitamin D status was linked to increased odds of prevalent sarcopenia. Over three years, low baseline 25OHD < 25 vs. ≥ 50 nmol/L were associated with greater loss of muscle mass and increased time for the Timed Up and Go test. The risk for developing incident sarcopenia was not significantly elevated in individuals with low baseline 25OHD but when including death as combined outcome alongside incident sarcopenia, there was a strong positive association in multivariable analysis [OR (95% CI) 3.19 (1.54-6.57) for 25OHD < 25 vs. ≥ 50 nmol/L]. There was no evidence for a PTH-mediating effect. Low baseline 25OHD levels were associated with unfavorable changes in muscle mass and physical performance, but not with incident sarcopenia. Future randomized trials are needed to assess causality and to address the issue of competing risks such as mortality in older cohorts.

12.
Eur Heart J ; 40(26): 2142-2151, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31098611

RESUMO

AIMS: We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). METHODS AND RESULTS: We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission. CONCLUSIONS: Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

13.
Horm Metab Res ; 51(9): 602-607, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132798

RESUMO

The aim of this study was to investigate any association between the adipose tissue-derived protein, visfatin, and non-alcoholic fatty liver disease (NAFLD) and its potential long-term impact on hepatic steatosis. A cross-sectional study including 2429 randomly selected subjects was performed in 2002. Later, 403 subjects were re-evaluated in 2013. Serum visfatin concentrations were determined by sandwich enzyme-linked immunosorbent assay. Phenotyping included abdominal ultrasonography, anthropometric data, and laboratory investigations. No association was found between circulating visfatin levels and the presence of NAFLD at baseline (2002: p=0.0967) or during follow-up (2013: p=0.1312). However, a significant increase in visfatin levels in relation to the level of steatosis was seen during follow-up (p<0.0001). During the more than 10-year follow-up, the metabolic status of the study subjects worsened, with a significant increase in body mass index (BMI) (p<0.0001), waist-to-hip ratio (p<0.0001), triglycerides (TG) (p<0.0001), low-density lipoprotein (p=0.0305), homeostasis model assessment (p<0.0001), and presence of diabetes (p<0.0001). This change was accompanied by an increase in serum visfatin levels, which showed a weak correlation with BMI (p<0.0001, r=0.27586) and presence of diabetes (p<0.0043, r=0.14188). A statistically significant correlation between leucocyte numbers and serum visfatin concentration (p<0.0001, r=0.25615) was found. We found no association between visfatin levels and the presence or absence of NAFLD or the degree of hepatic fatty infiltration at baseline. There was a strong correlation between serum visfatin concentrations and the number of leucocytes, which may suggest a proinflammatory role for visfatin.

14.
PLoS One ; 14(5): e0216222, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31075152

RESUMO

BACKGROUND: Fibrinogen is an essential hemostatic factor and cardiovascular disease risk factor. Early attempts at evaluating the causal effect of fibrinogen on coronary heart disease (CHD) and myocardial infraction (MI) using Mendelian randomization (MR) used single variant approaches, and did not take advantage of recent genome-wide association studies (GWAS) or multi-variant, pleiotropy robust MR methodologies. METHODS AND FINDINGS: We evaluated evidence for a causal effect of fibrinogen on both CHD and MI using MR. We used both an allele score approach and pleiotropy robust MR models. The allele score was composed of 38 fibrinogen-associated variants from recent GWAS. Initial analyses using the allele score used a meta-analysis of 11 European-ancestry prospective cohorts, free of CHD and MI at baseline, to examine incidence CHD and MI. We also applied 2 sample MR methods with data from a prevalent CHD and MI GWAS. Results are given in terms of the hazard ratio (HR) or odds ratio (OR), depending on the study design, and associated 95% confidence interval (CI). In single variant analyses no causal effect of fibrinogen on CHD or MI was observed. In multi-variant analyses using incidence CHD cases and the allele score approach, the estimated causal effect (HR) of a 1 g/L higher fibrinogen concentration was 1.62 (CI = 1.12, 2.36) when using incident cases and the allele score approach. In 2 sample MR analyses that accounted for pleiotropy, the causal estimate (OR) was reduced to 1.18 (CI = 0.98, 1.42) and 1.09 (CI = 0.89, 1.33) in the 2 most precise (smallest CI) models, out of 4 models evaluated. In the 2 sample MR analyses for MI, there was only very weak evidence of a causal effect in only 1 out of 4 models. CONCLUSIONS: A small causal effect of fibrinogen on CHD is observed using multi-variant MR approaches which account for pleiotropy, but not single variant MR approaches. Taken together, results indicate that even with large sample sizes and multi-variant approaches MR analyses still cannot exclude the null when estimating the causal effect of fibrinogen on CHD, but that any potential causal effect is likely to be much smaller than observed in epidemiological studies.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30892596

RESUMO

AIMS: Serum uromodulin has recently emerged as promising biomarker for kidney function and was suggested to be associated with type 2 diabetes (T2D) in coronary patients. Here, we analyzed the association of serum uromodulin with T2D in the population-based KORA F4/FF4 study. METHODS: In 1119 participants of the KORA F4 study aged 62 - 81 years, serum uromodulin was measured and the association of serum uromodulin with T2D was assessed using logistic and linear regression models stratified for sex. After a mean follow-up time of 6.5 years, 635 participants where reevaluated. Glucose tolerance status was determined by oral glucose tolerance test at baseline and at the follow-up examination except in cases of known T2D. RESULTS: Serum uromodulin was inversely associated with T2D in the crude analysis and after adjustment for age and BMI in men (p < 0.001) and in women (p < 0.05). After further adjustment for estimated glomerular filtration rate, serum uromodulin was significantly inversely associated with T2D in men (p < 0.001), but not in women. Serum uromodulin was not associated with prediabetes after multivariate adjustment and did not predict T2D in men or in women after the follow-up time of 6.5 ± 0.3 years. CONCLUSIONS: In participants of the KORA F4 study, serum uromodulin is independently associated with T2D in men, but is no predictor of future development of T2D.

16.
PLoS One ; 14(3): e0213334, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845176

RESUMO

OBJECTIVE: Patients with coronary heart disease (CHD) commonly suffer from depression and anxiety, yet transitions of symptom severity and cardiovascular events (CVE) over time are not well characterized. METHODS: We included 997 patients with stable CHD from a prospective cohort study. We estimated 5- and 10-year transition probabilities of depression and anxiety symptom severity levels and fatal- and non-fatal adverse CVE. Depression and anxiety symptoms were measured with the Hospital Anxiety and Depression Scale 5 times over 13 years and categorized as no, mild, or moderate/severe symptoms. Using multi-state modeling, we calculated 5- and 10-year transition probabilities for depression and anxiety symptom severity and CVE and calculated transition intensity ratios for factors associated with symptom severity progression and regression. RESULTS: At 5 years, only approximately half of participants with moderate or severe symptom severity at baseline transitioned to no symptom severity. Patients with low physical activity (<1x/week or never) had a higher probability of worse symptom severity after 5 and 10 years and a higher probability of a CVE after 5 and 10 years regardless of their depression status at baseline compared to higher physical activity groups. Higher body mass index, <10 years of education, and lower physical activity were associated with depression symptom progression; female and lower physical activity were associated with anxiety symptom progression. CONCLUSIONS: Patients with CHD had a consistent burden of depression and anxiety symptoms. Secondary prevention strategies should target depression and anxiety and include a physical activity component.

17.
Dtsch Med Wochenschr ; 144(5): 315-321, 2019 03.
Artigo em Alemão | MEDLINE | ID: mdl-30836402

RESUMO

Since the early 1990 s, both experimental and clinical data have clearly demonstrated that inflammatory processes accompany atherosclerotic disease from its initiation to the development of clinical complications. Numerous biomarkers involved at various levels of the inflammation cascade have been shown to be associated with adverse cardiovascular outcomes. Among them, the classical acute phase reactant C-reactive protein (CRP) has been most intensively investigated. Recent research in this field has been driven by the observation that despite low LDL-cholesterol levels, a remarkably high number of patients are still at increased risk for recurrent cardiovascular events. This is argued to be attributable to the presence of a prolonged inflammatory response (reflected by a persistently elevated hsCRP), a concept, which is currently known as "residual inflammatory risk". The unequivocal proof that the inflammatory process is not only a simple bystander but is also causally involved in atherogenesis, came from the recent CANTOS trial, showing a 15 % reduction of primary MACE outcomes despite aggressive statin therapy and lower LDL-cholesterol levels. Thus, an anti-inflammatory treatment strategy might represent a promising tool to improve the outcome of this still deadly disease.


Assuntos
Aterosclerose , Inflamação , Biomarcadores/sangue , Proteína C-Reativa/análise , LDL-Colesterol/sangue , Humanos
18.
Dtsch Med Wochenschr ; 144(5): 322-328, 2019 03.
Artigo em Alemão | MEDLINE | ID: mdl-30836403

RESUMO

Atherosclerotic cardiovascular disease is the leading cause of premature mortality and morbidity worldwide. Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. The causality of plasma low-density lipoprotein-cholesterol (LDL-C) in the pathophysiology of cardiovascular disease has been established beyond any reasonable doubt. In this context, individual risk estimation, the determination of target values and lipid-lowering strategies represent an essential part and a challenge in the daily clinical practice to prevent cardiovascular events. Statins are recommended as first-line therapy for patients with hypercholesterolemia in secondary prevention. Controversies remain in the context of primary prevention, however, as to which kind of subjects to treat, the magnitude of the benefit, and potential harm. This article gives a brief overview of the current evidence, guideline recommendations and strategies for lowering of LDL-C in the primary prevention of cardiovascular disease.


Assuntos
Hipercolesterolemia , Prevenção Primária , Humanos , Hipercolesterolemia/prevenção & controle , Hipercolesterolemia/terapia , Guias de Prática Clínica como Assunto
19.
Age Ageing ; 48(4): 541-546, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30855645

RESUMO

BACKGROUND: Growth differentiation factor 15 (GDF-15) has been associated with many adverse age-related outcomes and other age-related disorders. The aim of the study was to investigate if baseline levels of GDF-15 are associated with total mortality in community living, older adults during eight years of follow-up after simultaneous consideration of key biomarkers and functional parameters. METHODS: prospective cohort study including 1,470 community-dwelling older adults aged 65 years or older. GDF-15 was measured by ElectroChemi-Lumisnescence Immunoassays (Roche, Mannheim, Germany). We used Cox-proportional hazards regression to estimate the association of GDF-15 levels with 8-year all-cause mortality. RESULTS: GDF-15 levels were independently of age and sex strongly associated with many biomarkers such as CRP, IL-6, NT-proBNP, hs-troponines as well as with lipids, metabolic and endocrine markers and kidney function (all P-values < 0.001). GDF-15 showed also a statistically significant correlation to gait speed, hand grip strength and walking duration. In addition, we found a consistent association between levels of GDF-15 and risk of subsequent all-cause mortality which persisted after additional adjustment for key markers of inflammation, cardiac function and damage, and physical function. The hazard ratio (HR) per unit increase of log-transformed GDF-15 was 1.72 (95% CI 1.35; 2.18). CONCLUSIONS: GDF-15 levels were not only strongly associated with many functional parameters and key biomarkers independently of age and sex, but also with 8-year all-cause mortality even after adjusting for gait speed, NT-proBNP and hs-TnT.

20.
Clin Chem ; 65(7): 849-861, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30917972

RESUMO

BACKGROUND: Anemia has been shown to be a risk factor for coronary artery disease (CAD) and mortality, whereas the role of iron metabolism remains controversial. METHODS: We analyzed iron metabolism and its associations with cardiovascular death and total mortality in patients undergoing coronary angiography with a median follow-up of 9.9 years. Hemoglobin and iron status were determined in 1480 patients with stable CAD and in 682 individuals in whom significant CAD had been excluded by angiography. RESULTS: Multivariate-adjusted hazard ratios (HRs) for total mortality in the lowest quartiles of iron, transferrin saturation, ferritin, soluble transferrin receptor (sTfR), and hemoglobin were 1.22 (95% CI, 0.96-1.60), 1.23 (95% CI, 0.97-1.56), 1.27 (95% CI, 1.02-1.58), 1.26 (95% CI, 0.97-1.65), and 0.99 (95% CI, 0.79-1.24), respectively, compared to the second or third quartile, which served as reference (1.00) because of a J-shaped association. The corresponding HRs for total mortality in the highest quartiles were 1.44 (95% CI, 1.10-1.87), 1.37 (95% CI, 1.05-1.77), 1.17 (95% CI, 0.92-1.50), 1.76 (95% CI, 1.39-2.22), and 0.83 (95% CI, 0.63-1.09). HRs for cardiovascular death were similar. For hepcidin, the adjusted HRs for total mortality and cardiovascular deaths were 0.62 (95% CI, 0.49-0.78) and 0.70 (95% CI, 0.52-0.90) in the highest quartile compared to the lowest one. CONCLUSIONS: In stable patients undergoing angiography, serum iron, transferrin saturation, sTfR, and ferritin had J-shaped associations and hemoglobin only a marginal association with cardiovascular and total mortality. Hepcidin was continuously and inversely related to mortality.

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