Summary
Background
Antiplatelet therapy is the standard treatment for the prevention of cardiovascular events (CVEs). High on‐treatment platelet reactivity (HPR) is a risk factor for secondary CVEs ...in patients prescribed aspirin and/or clopidogrel. The present review and meta‐analysis was aimed at assessing the ability of individual platelet‐function tests to reliably identify patients at risk of developing secondary CVEs.
Methods and Results
A systematic literature search was conducted to identify studies on platelet‐reactivity measurements and CVEs. The main inclusion criteria were: (i) prospective study design; (ii) study medication, including aspirin and/or clopidogrel; and (iii) a platelet‐function test being performed at baseline, before follow‐up started. Of 3882 identified studies, 102 (2.6%; reporting on 44 098 patients) were included in the meta‐analysis. With regard to high on‐aspirin platelet reactivity (HAPR), 22 different tests were discussed in 55 studies (22 441 patients). Pooled analysis showed that HAPR was diagnosed in 22.2% of patients, and was associated with an increased CVE risk (relative risk RR 2.09; 95% confidence interval CI 1.77–2.47). Eleven HAPR tests independently showed a significantly increased CVE risk in patients with HAPR as compared with those with normal on‐aspirin platelet reactivity. As regards high on‐clopidogrel platelet reactivity (HCPR), 59 studies (34 776 patients) discussed 15 different tests, and reported that HCPR was present in 40.4% of patients and was associated with an increased CVE risk (RR 2.80; 95% CI 2.40–3.27). Ten tests showed a significantly increased CVE risk.
Conclusions
Patients with HPR are suboptimally protected against future cardiovascular complications. Furthermore, not all of the numerous platelet tests proved to be able to identify patients at increased cardiovascular risk.
Summary
The plasma concentration of adiponectin, an adipokine that has anti‐inflammatory, anti‐atherogenic and insulin sensitizing properties, is lower in obese subjects and could therefore be a ...target for therapy. In order to review and meta‐analyse prospective cohort studies investigating adiponectin concentration and the risk for incident coronary heart disease (CHD) or stroke, a systematic search of MEDLINE, EMBASE and Cochrane databases was performed. Two independent reviewers selected prospective cohort studies investigating the relationship between adiponectin level and incident CHD or stroke using ‘adiponectin’ and ‘cardiovascular disease’ or ‘stroke’ and their synonyms, excluding patients with clinically manifest vascular disease. Random‐effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI). Generalized least squares regression was used to assess dose–response relationships for adiponectin concentrations from studies that provided RRs solely based upon categorical data regression. In total, 16 prospective cohort studies, comprising 23,919 patients and 6,870 CHD or stroke outcome events, were included in the meta‐analyses. An increase of 1 standard deviation in log‐transformed adiponectin did not lower the risk for CHD (RR 0.97; 95% CI 0.86–1.09). A 10 μg mL–1 increase in adiponectin conferred a RR of 0.91 (95% CI 0.80–1.03) for CHD and a RR 1.01 (95% CI 0.97–1.06) for stroke. In conclusion, plasma adiponectin is not related to the risk for incident CHD or stroke.
Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic ...low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients.
Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria.
307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2-11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01-1.46 and HR 1.26, 95% CI 1.10-1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease.
Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Obesity and risk of bleeding: the SMART study Braekkan, S. K.; Graaf, Y.; Visseren, F. L. J. ...
Journal of thrombosis and haemostasis,
January 2016, 2016-Jan, 2016-01-00, 20160101, Letnik:
14, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Essentials
Whether obesity protects against clinically relevant bleeding is unclear.
We investigated the risk of bleeding according to various measures of obesity in a cohort of 9736 patients.
...Obesity was not associated with a lower risk of bleeding.
The procoagulant profile in obese subjects may not be enough to protect against clinically relevant bleeding.
Summary
Background
Obesity is associated with increased levels of procoagulant factors and decreased fibrinolytic activity. Whether this hemostatic profile protects against clinically relevant bleeding has been scarcely investigated.
Objectives
To assess the impact of measures of obesity on the risk of bleeding in a large cohort of patients at increased atherothrombotic risk.
Methods
The Second Manifestation of ARTerial disease (SMART) study included 9736 patients aged 18–79 years, followed for a median of 5.9 years. Body mass index (BMI), waist circumference and hip circumference were measured at inclusion. All incident fatal or non‐fatal hemorrhagic events were recorded.
Results
During follow‐up, 359 first bleeding events occurred. In quintile‐based analyses, the risk of bleeding was highest in the lowest quintile (Q) of BMI (age and sex‐adjusted HR Q2 vs. Q1, 0.68; 95% CI, 0.50–0.94), but there was a threshold effect at low BMI levels (men, < 23.84 kg m−2; women, < 22.49 kg m−2), and the risk estimates for bleeding did not further change across the remaining quintiles (HR Q3 0.81 and Q5 0.75). For waist circumference the relationship appeared to be U‐shaped, with the lowest risk of bleeding in quintile 3 (HR Q3 vs. Q1, 0.69; 95% CI, 0.46–1.04). Adjustments for hypertension, hemoglobin level, renal failure, diabetes and use of oral anticoagulants or platelet inhibitors did not affect the results.
Conclusion
Obesity was not associated with lower risk of bleeding. Our findings suggest that presumed protection against bleeding due to an apparently efficient hemostatic system may be counterbalanced by other factors in obese subjects.
Essentials
The association between chronic kidney disease and bleeding is unknown.
We followed 10 347 subjects at high cardiovascular risk for bleeding events.
Chronic kidney disease was associated ...with a 1.5‐fold increased bleeding risk.
Especially albuminuria rather than decreased kidney function was associated with bleeding events.
Summary
Background
There are indications that patients with chronic kidney disease have an increased bleeding risk.
Objectives
To investigate the association between chronic kidney disease and bleeding in patients at high cardiovascular risk.
Methods
We included 10 347 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2015 for an outpatient visit with classic risk factors for arterial disease or with symptomatic arterial disease (Second Manifestation of Arterial disease SMART cohort). Patients were staged according to the KDIGO guidelines, on the basis of estimated glomerular filtration rate (eGFR) and albuminuria, and were followed for the occurrence of major hemorrhagic events until March 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding were calculated with Cox proportional hazards analyses.
Results
The incidence rate for bleeding in subjects with chronic kidney disease was 8.0 per 1000 person‐years and that for subjects without chronic kidney disease was 3.5 per 1000 person‐years. Patients with chronic kidney disease (n = 2443) had a 1.5‐fold (95% CI 1.2–1.9) increased risk of bleeding as compared with subjects without chronic kidney disease (n = 7904) after adjustment. Subjects with an eGFR of < 45 mL min−1 1.73 m–2 with albuminuria had a 3.5‐fold (95% CI 2.3–5.3) increased bleeding risk, whereas an eGFR of < 45 mL min−1 1.73 m–2 without albuminuria was not associated with an increased bleeding risk (HR 1.3, 95% CI 0.7–2.5).
Conclusion
Chronic kidney disease is a risk factor for bleeding in patients with classic risk factors for arterial disease or with symptomatic arterial disease, especially in the presence of albuminuria.
To investigate whether severity and progression of periventricular and deep white matter lesions (WML) and lacunar infarcts were associated with progression of brain atrophy.
Within the SMART-MR ...study, a prospective cohort on MRI changes in patients with symptomatic atherosclerotic disease, 565 patients (57 ± 9 years) without large infarcts had vascular screening and 1.5 T MRI at baseline and after a mean follow-up of 3.9 years. With automated brain segmentation, total brain, cortical gray matter, ventricular, and WML volumes were estimated and expressed relative to intracranial volume (%). Lacunar infarcts were rated manually.
Using linear regression analyses adjusted for demographics and vascular risk factors, periventricular WML volume at baseline was associated with greater decrease in cortical gray matter volume (B = -1.73%, 95% confidence interval CI -3.15% to -0.30%, per 1% WML volume increase) and greater increase in ventricular volume (B = 0.12%, 95% CI 0.04% to 0.20%). Progression of periventricular WML volume corresponded with a greater decrease in cortical gray matter volume (B = -0.45%, 95% CI -0.9% to 0%) and greater increase in ventricular volume (B = 0.15%, 95% CI 0.1% to 0.2%). Presence of lacunar infarcts was associated with greater decline in total brain volume (B = -0.25%, 95% CI -0.49% to -0.01%) and progression of lacunar infarcts with a greater decrease of total brain (B = -0.30%, 95% CI -0.59% to 0.01%) and cortical gray matter volume (B = -0.81%, 95% CI -1.43% to -0.20%).
In patients with symptomatic atherosclerotic disease, presence and progression of periventricular WML and lacunar infarcts is associated with greater progression of brain atrophy independent of vascular risk factors.
Various cardiovascular prediction models have been developed for patients with type 2 diabetes. Their predictive performance in new patients is mostly not investigated. This study aims to quantify ...the predictive performance of all cardiovascular prediction models developed specifically for diabetes patients.
Follow-up data of 453, 1174 and 584 type 2 diabetes patients without pre-existing cardiovascular disease (CVD) in the EPIC-NL, EPIC-Potsdam and Secondary Manifestations of ARTerial disease cohorts, respectively, were used to validate 10 prediction models to estimate risk of CVD or coronary heart disease (CHD). Discrimination was assessed by the c-statistic for time-to-event data. Calibration was assessed by calibration plots, the Hosmer-Lemeshow goodness-of-fit statistic and expected to observed ratios.
There was a large variation in performance of CVD and CHD scores between different cohorts. Discrimination was moderate for all 10 prediction models, with c-statistics ranging from 0.54 (95% CI 0.46 to 0.63) to 0.76 (95% CI 0.67 to 0.84). Calibration of the original models was poor. After simple recalibration to the disease incidence of the target populations, predicted and observed risks were close. Expected to observed ratios of the recalibrated models ranged from 1.06 (95% CI 0.81 to 1.40) to 1.55 (95% CI 0.95 to 2.54), mainly driven by an overestimation of risk in high-risk patients.
All 10 evaluated models had a comparable and moderate discriminative ability. The recalibrated, but not the original, prediction models provided accurate risk estimates. These models can assist clinicians in identifying type 2 diabetes patients who are at low or high risk of developing CVD.
Aims
To predict individualized treatment effects of angiotensin receptor blockers (ARBs) on cardiovascular and renal complications in order to help clinicians and patients assess the benefit of ...treatment (or adherence) and estimate remaining disease risk.
Materials and methods
In patients with diabetic nephropathy, the 3‐year treatment effect of ARBs was predicted in terms of absolute risk reduction (ARR) for end‐stage renal disease (ESRD) and cardiovascular disease (CVD; i.e. myocardial infarction, stroke, hospitalization for heart failure) and all‐cause mortality. Competing‐risk‐adjusted proportional hazard models were developed based on the Irbesartan Diabetic Nephropathy Trial (IDNT) and externally validated in the Reduction of Endpoints NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial.
Results
Predictors included in the model were age, sex, smoking sex, systolic blood pressure, urinary albumin/creatinine ratio, estimated glomerular filtration rate, albumin and phosphorus. The median predicted 3‐year risk without treatment was 6.0% for ESRD and 28.0% for CVD and mortality. The median interquartile range (IQR) predicted 3‐year ARR was 1.2 (0.4‐3.1)% for ESRD and 2.2 (1.8‐2.6)% for CVD and mortality, resulting in a combined ARR of 3.4 (2.4‐5.5)%. The remaining disease risk was 4.7 (IQR 1.7‐12.8)% for ESRD and 25.8% (IQR 20.3‐31.9)% for CVD and mortality.
Conclusions
The combined effects of ARBs on ESRD and CVD and mortality in patients with diabetic nephropathy vary considerably between patients. A substantial proportion of patients remain at high risk for both outcomes despite ARB treatment.
Pharmacological lowering of inflammation has proven effective in reducing recurrent cardiovascular event rates. Aim of the current study is to evaluate lifestyle changes (smoking cessation, weight ...loss, physical activity level increase, alcohol moderation, and a summary lifestyle improvement score) in relation to change in plasma C-reactive protein (CRP) concentration in patients with established cardiovascular disease.
In total, 1794 patients from the UCC-SMART cohort with stable cardiovascular disease and CRP levels ≤10 mg/L, who returned for a follow-up study visit after median 9.9 years (IQR 5.4–10.8), were included. The relation between changes in smoking status, weight, physical activity, alcohol consumption, a summary lifestyle improvement score and change in plasma CRP concentration was evaluated with linear regression analyses.
Smoking cessation was related to a 0.40 mg/L decline in CRP concentration (β-coefficient −0.40; 95%CI -0.73,-0.07). Weight loss (per 1SD = 6.4 kg) and increase in physical activity (per 1 SD = 48 MET hours per week) were related to a decrease in CRP concentration (β-coefficients −0.25; 95%CI -0.33,-0.16 and −0.09; 95%CI -0.17,-0.01 per SD). Change in alcohol consumption was not related to CRP difference. Every point higher in the summary lifestyle improvement score was related to a decrease in CRP concentration of 0.17 mg/L (β-coefficient −0.17; 95%CI -0.26,-0.07).
Smoking cessation, increase in physical activity, and weight loss are related to a decrease in CRP concentration in patients with stable cardiovascular disease. Patients with the highest summary lifestyle improvement score have the most decrease in CRP concentration. These results may indicate that healthy lifestyle changes contribute to lowering systemic inflammation, potentially leading to a lower cardiovascular risk in patients with established cardiovascular disease.
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•In patients with established cardiovascular disease (CVD), lifestyle improvements are related to a decrease in C-reactive protein (CRP).•These lifestyle improvements are smoking cessation, physical activity increase, and weight loss.•Multiple lifestyle changes are related to the most decrease in CRP concentration.•Lifestyle changes might reduce CVD risk partly through lowering systemic inflammation.
Objectives
To report the variation in computed tomography perfusion (CTP) arterial input function (AIF) in a multicenter stroke study and to assess the impact this has on CTP results.
Methods
CTP ...datasets from 14 different centers were included from the DUtch acute STroke (DUST) study. The AIF was taken as a direct measure to characterize contrast bolus injection. Statistical analysis was applied to evaluate differences in amplitude, area under the curve (AUC), bolus arrival time (BAT), and time to peak (TTP). To assess the clinical relevance of differences in AIF, CTP acquisitions were simulated with a realistic anthropomorphic digital phantom. Perfusion parameters were extracted by CTP analysis using commercial software (IntelliSpace Portal (ISP), version 10.1) as well as an in-house method based on block-circulant singular value decomposition (bSVD).
Results
A total of 1422 CTP datasets were included, ranging from 6 to 322 included patients per center. The measured values of the parameters used to characterize the AIF differed significantly with approximate interquartile ranges of 200–750 HU for the amplitude, 2500–10,000 HU·s for the AUC, 0–17 s for the BAT, and 10–26 s for the TTP. Mean infarct volumes of the phantom were significantly different between centers for both methods of perfusion analysis.
Conclusions
Although guidelines for the acquisition protocol are often provided for centers participating in a multicenter study, contrast medium injection protocols still vary. The resulting volumetric differences in infarct core and penumbra may impact clinical decision making in stroke diagnosis.
Key Points
• The contrast medium injection protocol may be different between stroke centers participating in a harmonized multicenter study.
• The contrast medium injection protocol influences the results of X-ray computed tomography perfusion imaging.
• The contrast medium injection protocol can impact stroke diagnosis and patient selection for treatment.
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