Factors predicting cardiovascular events in chronic kidney disease patients. Role of subclinical atheromatosis extent assessed by vascular ultrasound

<div><p>Patients with chronic kidney disease (CKD) have an increased incidence of cardiovascular events (CVE). The contribution of subclinical atheromatosis extent, including femoral arteries, to CVE in CKD patients has not been investigated. In this paper, we examine the prognostic value of subclinical atheromatosis extent, assessed as the number of arterial territories with plaque, in predicting the incidence of major and minor CVE. The NEFRONA is a multicenter, prospective cohorts study that recruited 2445 CKD subjects and 559 controls, free from previous cardiovascular disease, in 81 medical centers across Spain. The presence of atheroma plaque was assessed by arterial ultrasound in ten arterial territories (carotid and femoral). The predictive power of the presence or absence of atheroma plaque in any territory was compared with the quantification of atheroma extent as the number of territories with plaque. During the median follow up of 48 months, 216 CVE were reported. Factors predicting the incidence of CVE in the whole cohort were being male, CKD patient, lower levels of 25(OH) vitamin D, higher levels of cholesterol and the extent of subclinical atheromatosis, yielding a higher concordance (C) index than the presence or absence of plaque. In stratified analysis including specific factors of CKD patients not on dialysis, the variables predicting CVE were the same as in the whole cohort, plus higher levels of potassium. Again, the inclusion of the information about atheromatosis as number of territories with plaque, presented a higher C index than the presence or absence of plaque. In the dialysis population, significant variables were older age, diabetes, dialysis vintage and higher levels of cholesterol and phosphate. In this case the higher C index was obtained with the information about plaque presence.</p><p>Subclinical atheromatosis extent, including femoral arteries, influences CVE in CKD and its detection could improve the prediction of cardiovascular events.</p></div

Bivariate analysis of the basal characteristics of the CKD patients not on dialysis in the NEFRONA cohort according to the incidence of CVE.

<p>Quantitative data are expressed as mean and standard deviation (SD) or median, (p25, p75) depending on the normality of the distribution. Qualitative variables are expressed as N (%). HR: Hazard ratio; CI95%: 95% confidence interval. SBP: systolic blood pressure; PP: pulse pressure; cIMT: intima media thickness; ABI: ankle-brachial index; hsCRP: high sensitivity C-reactive protein. Ref: Reference.</p

Bivariate analysis of the basal characteristics of the NEFRONA cohort according to the incidence of CVE.

<p>Quantitative data are expressed as mean and standard deviation (SD) or median, (p25, p75) depending on the normality of the distribution. Qualitative variables are expressed as N (%). HR: Hazard ratio; CI95%: 95% confidence interval. SBP: systolic blood pressure; PP: pulse pressure; cIMT: intima media thickness; ABI: ankle-brachial index; hsCRP: high sensitivity C-reactive protein. Ref: Reference.</p

Multivariate competing risk regression to model the incidence of CVE.

<p>Results are expressed as Hazard Ratios (HR; *Exponential β for independent variables with interactions) and 95% Confidence interval (95% CI). The variables introduced to build multivariate models were all the significant variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186665#pone.0186665.t001" target="_blank">Table 1</a> plus any potential confounder.</p

Kaplan-Meier curve showing the unadjusted incidence of CVE along the follow up time (months) depending on (A) the presence or absence of atheroma plaque (p<0.000 Mantel-Haenzel) or (B) the number of arterial territories with atheroma plaque (p<0.000 Mantel-Haenzel linear trend).

<p>Kaplan-Meier curve showing the unadjusted incidence of CVE along the follow up time (months) depending on (A) the presence or absence of atheroma plaque (p<0.000 Mantel-Haenzel) or (B) the number of arterial territories with atheroma plaque (p<0.000 Mantel-Haenzel linear trend).</p

Bivariate analysis of the basal characteristics of the dialysis patients in the NEFRONA cohort according to the incidence of CVE.

<p>Quantitative data are expressed as mean and standard deviation (SD) or median, (p25, p75) depending on the normality of the distribution. Qualitative variables are expressed as N (%). HR: Hazard ratio; CI95%: 95% confidence interval. SBP: systolic blood pressure; PP: pulse pressure; cIMT: intima media thickness; ABI: ankle-brachial index; hsCRP: high sensitivity C-reactive protein. Ref: Reference.</p

Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium

OBJECTIVE:To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. DESIGN:Individual participant data meta-analysis. SETTING:Cohorts from 40 countries with data collected between 1970 and 2017. PARTICIPANTS:Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607). MAIN OUTCOME MEASURES:GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality. RESULTS:Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. CONCLUSIONS:Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR