Aortic Calcification and Arterial Stiffness Burden in a Chronic Kidney Disease Cohort with High Cardiovascular Risk: Baseline Characteristics of the Impact of Phosphate Reduction On Vascular End-Points in Chronic Kidney Disease Trial

Abstract

Chronic kidney disease (CKD) is associated with excess cardiovascular morbidity and mortality compared to the general population. Hyperphosphataemia, associated with vascular calcification and arterial stiffness, may play a key role in the pathogenesis of cardiovascular disease (CVD) associated with CKD, although phosphate reduction strategies have not consistently proven to beneficially affect clinically relevant outcomes. The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) study is an international, multi-centre, randomized, placebo-controlled trial investigating the effect of the phosphate binder lanthanum carbonate on intermediate cardiovascular markers in patients with stage 3b–4 CKD. The primary end-point is change in carotid-femoral pulse wave velocity (PWV, SphygmoCor) after 96 weeks. Secondary outcomes include change in abdominal aortic calcification (AAC, computed tomography), serum phosphate and fibroblast growth factor 23 (FGF-23). In total, 278 participants were recruited and randomized, mean age 63 ± 13 years, 69% male, 45% diabetes, 32% CVD, 33% stage 3b CKD and 67% stage 4 CKD. Mean estimated glomerular filtration rate and serum phosphate were 26.6 ± 8.3 mL/min/1.72 m2 and 1.25 ± 0.20 mmol/L, respectively. Median (interquartile range) intact and c-terminal FGF-23 levels were 133.0 (89.1–202) pg/mL and 221.1 (154.3–334.1) RU/mL, respectively. Mean PWV was 10.8 ± 3.6 m/s and 81% had AAC (median Agatston score 1,535 [63–5,744] Hounsfield units). PWV ≥10 m/s was associated with older age, diabetes, CVD, presence of AAC, higher systolic blood pressure (BP), larger waist circumference and higher alkaline phosphatase. AAC was associated with older age, male sex, diabetes, CVD, higher diastolic BP, dyslipidaemia (and use of statins), smoking, larger waist circumference and increased PWV. In conclusion, IMPROVE-CKD participants had high baseline risk for cardiovascular events, as suggested by high baseline PWV and AAC values.

High Pulse Wave Velocity Is Associated With Decreased Macular Vessel Density in Normal-Tension Glaucoma

“…Moreover, PWV has been associated with DM, 50,51 abnormal lipid metabolism, 52,53 smoking, 54 elevated uric acid levels, 55 high body mass index, 56 and chronic kidney disease. 57,58 Although we included all the possible systemic factors influencing PWV as covariates, mVD was still significantly associated with PWV in patients with NTG in the multivariate logistic regression analysis.…”

State of the Art Review: Brachial-Ankle PWV

“…Risk factors for CKD, such as hypertension and diabetes mellitus, act directly to increase the arterial stiffness 18 , 19 , 22 , 23 ) , and in some studies, the PWV was higher in subjects with diabetic CKD than in those with non-diabetic CKD 41 ) . Even so, increased arterial stiffness has been observed even in the early stages of CKD 42 – 45 ) , and vascular calcification related to advanced CKD may augment this increase in arterial stiffness 45 ) . Recently, the ARIC study reported that the estimated glomerular filtration rate is more closely associated with the carotid-femoral PWV than with the brachial-ankle/heart-ankle PWV 46 ) .…”

“…Details of the underlying mechanisms are described in section 4-2. Conversely, hypertension, diabetes mellitus and CKD also contribute to the progression of arterial stiffening 16 – 19 , 22 , 23 , 41 – 45 ) , thus forming a vicious cycle 63 , 64 ) , which may exacerbate the risk status for CVD ( Fig. 2 ).…”

Epidemiology of kidney disease: consolidating and integrating the evidence to improve kidney care from early childhood to adulthood

“…These 2 publications are pivotal in defining the risk factors of disease progression and cardiovascular complications in people with kidney disease. Based on these studies, novel intervention trials, such as the SHARP, 6 CKD-FIX, 7 and IMPROVE-CKD, 8 have since been conducted to test whether such treatments as lipid-lowering therapies, allopurinol, and phosphate binders may reduce the risk of vascular disease and renal progression in highrisk individuals with moderate-to advancedstage CKD. Although the findings of these intervention trials are largely negative, they are crucial in refining and asking the important research questions.…”