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      Carotid intima-media thickness is an independent predictor of all-cause mortality and cardiovascular morbidity in patients with diabetes mellitus type 2 and chronic kidney disease

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          Abstract

          Background: Intima-Media-Thickness of the carotid artery wall (cIMT) is a strong predictor of cardiovascular (CV) disease. The aim of this study was to investigate the significance of cIMT as an independent prognostic factor for CV morbidity and mortality in patients with chronic kidney disease (CKD) and diabetes mellitus type 2 (DM2).

          Methods: The study included 142 diabetic patients in different stages of CKD. Patients were categorized into two groups according to low (≤0.86 mm) or high cIMT (>0.86 mm), respectively. CV events and death from all causes were registered during a seven-year follow-up.

          Results: Mean age, BMI and duration of diabetes were 68 years (range: 45–90), >30 kg/m 2 and 15 years (range: 5–40), respectively. Patients with increased cIMT were older, suffered from a lower estimated glomerular filtration rate (eGFR), peripheral atherosclerosis and plaque presence in either carotid artery. Increased BMI (beta= −0.29, p = .01), lower eGFR (beta = 0.353, p = .003) and male gender (beta= −0.339, p = .005) were found to predict increased cIMT. Predictors of all-cause mortality in Cox proportional hazard models were low eGFR and high cIMT with HR = 0.96 (CI = 0.94–0.98), p < .001 and HR = 2.9 (CI = 1.03–7.99), p = .04, respectively. The risk of future CV event was determined by albuminuria and cIMT with HR = 1 (CI = 1.0–1.0), p < .001 and HR = 2.04 (CI = 1.1–3.78), p = .02, respectively. Patients with high cIMT presented significantly higher all-cause mortality and a new CV event ( p = .005/ p = .018, respectively).

          Conclusions: cIMT is a strong and independent predictor of CV morbidity and mortality, and should be considered a valuable tool for the stratification of CV risk in patients with CKD and DM2.

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          Most cited references20

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          Carotid intima-media thickness and plaque in cardiovascular risk assessment.

          Carotid intima-media thickness (CIMT) has been shown to predict cardiovascular (CV) risk in multiple large studies. Careful evaluation of CIMT studies reveals discrepancies in the comprehensiveness with which CIMT is assessed-the number of carotid segments evaluated (common carotid artery [CCA], internal carotid artery [ICA], or the carotid bulb), the type of measurements made (mean or maximum of single measurements, mean of the mean, or mean of the maximum for multiple measurements), the number of imaging angles used, whether plaques were included in the intima-media thickness (IMT) measurement, the report of adjusted or unadjusted models, risk association versus risk prediction, and the arbitrary cutoff points for CIMT and for plaque to predict risk. Measuring the far wall of the CCA was shown to be the least variable method for assessing IMT. However, meta-analyses suggest that CCA-IMT alone only minimally improves predictive power beyond traditional risk factors, whereas inclusion of the carotid bulb and ICA-IMT improves prediction of both cardiac risk and stroke risk. Carotid plaque appears to be a more powerful predictor of CV risk compared with CIMT alone. Quantitative measures of plaques such as plaque number, plaque thickness, plaque area, and 3-dimensional assessment of plaque volume appear to be progressively more sensitive in predicting CV risk than mere assessment of plaque presence. Limited data show that plaque characteristics including plaque vascularity may improve CV disease risk stratification further. IMT measurement at the CCA, carotid bulb, and ICA that allows inclusion of plaque in the IMT measurement or CCA-IMT measurement along with plaque assessment in all carotid segments is emerging as the focus of carotid artery ultrasound imaging for CV risk prediction.
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            Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study.

            Data are limited with regard to the relations of low-grade albuminuria (below the microalbuminuria threshold) and incidence of cardiovascular disease (CVD) events in nondiabetic, nonhypertensive individuals. We examined the association of urinary albumin excretion (spot urine albumin indexed to creatinine [UACR]) and the incidence of CVD events and all-cause mortality in 1568 nonhypertensive, nondiabetic Framingham Offspring Study participants (mean age, 55 years; 58% women) free of CVD. On follow-up (median, 6 years), 54 participants (20 women) developed a first CVD event, and 49 (19 women) died. After adjustment for established risk factors, increasing UACR was associated with greater risk of CVD (hazards ratio [HR] per SD increment in log UACR, 1.36; 95% CI, 1.00 to 1.87) and death (HR per SD increment in log UACR, 1.55; 95% CI, 1.10 to 2.20). Participants with UACR greater than or equal to the sex-specific median (> or =3.9 microg/mg for men, > or =7.5 microg/mg for women) experienced a nearly 3-fold risk of CVD (adjusted HR, 2.92; 95% CI, 1.57 to 5.44; P<0.001) and a borderline significantly increased risk of death (adjusted HR, 1.75; 95% CI, 0.95 to 3.22; P=0.08) compared with those with UACR below the median. The increased CVD risk associated with UACR at or above the median remained robust in analyses restricted to individuals without microalbuminuria (n=1470) and in subgroups with intermediate (n=1469) and low (n=1186) pretest probabilities of CVD. In our community-based sample of middle-aged nonhypertensive, nondiabetic individuals, low levels of urinary albumin excretion well below the current microalbuminuria threshold predicted the development of CVD. Our observations add to the growing body of evidence that challenges the notion that UACR <30 microg/mg indicates "normal" albumin excretion.
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              Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study.

              Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction. Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged > or = 65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (> 3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72% (95% CI, 1.46 to 2.01) increased risk for CVD death and a 52% (95% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54% for CVD death and 79% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic. In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.
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                Author and article information

                Journal
                Ren Fail
                Ren Fail
                IRNF
                irnf20
                Renal Failure
                Taylor & Francis
                0886-022X
                1525-6049
                2019
                26 March 2019
                : 41
                : 1
                : 131-138
                Affiliations
                [a ]Department of Nephrology, “Democritus” University of Thrace, Medical School, University General Hospital of Alexandroupolis , Alexandroupolis, Greece;
                [b ]Department of Vascular Surgery, “Democritus” University of Thrace, Medical School, University General Hospital of Alexandroupolis , Alexandroupolis, Greece;
                [c ]Laboratory of Pharmacology, “Democritus” University of Thrace, Medical School , Alexandroupolis, Greece
                Author notes
                CONTACT George S. Georgiadis ggeorgia@ 123456med.duth.gr , georgiadis_gs@ 123456hol.gr Department of Vascular Surgery, “Democritus” University of Thrace, Medical School, University General Hospital of Alexandroupolis , Alexandrou Papanastasiou 7 str, Alexandroupolis68131, Greece
                Article
                1585372
                10.1080/0886022X.2019.1585372
                6442115
                30909780
                9232b92b-c517-4ba4-b14d-52ff1d76b408
                © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 September 2018
                : 27 December 2018
                : 17 February 2019
                Page count
                Figures: 2, Tables: 5, Pages: 13, Words: 5248
                Categories
                Clinical Study

                Nephrology
                carotid intima-media thickness,diabetes mellitus type 2,cardiovascular disease
                Nephrology
                carotid intima-media thickness, diabetes mellitus type 2, cardiovascular disease

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