02957nas a2200373 4500008004100000022001400041245013400055210006900189260001300258300000900271490000800280520182700288653000902115653002502124653002802149653002802177653003002205653001102235653001402246653003202260653001702292100002502309700001902334700001602353700002402369700002502393700002002418700002402438700001902462700002202481700002402503700002002527856003602547 2014 eng d a1879-148400aFibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study.0 aFibroblast growth factor 23 the anklebrachial index and incident c2014 Mar a91-60 v2333 a

BACKGROUND: Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.

METHODS: Using data (N = 3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.

RESULTS: The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1-1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI < 0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76-1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75-1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28-3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79-2.70).

CONCLUSIONS: In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.

10aAged10aAnkle Brachial Index10aCardiovascular Diseases10aCross-Sectional Studies10aFibroblast Growth Factors10aHumans10aIncidence10aPeripheral Arterial Disease10aRisk Factors1 aGarimella, Pranav, S1 aIx, Joachim, H1 aKatz, Ronit1 aChonchol, Michel, B1 aKestenbaum, Bryan, R1 ade Boer, Ian, H1 aSiscovick, David, S1 aShastri, Shani1 aHiramoto, Jade, S1 aShlipak, Michael, G1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/623904500nas a2200337 4500008004100000022001400041245014900055210006900204260001300273300001200286490000600298520343400304100002503738700002403763700001803787700002003805700001903825700002103844700001903865700002203884700001703906700002403923700002503947700002303972700002203995700001804017700001904035700002404054710004804078856003604126 2017 eng d a2213-859500aMeasures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data.0 aMeasures of chronic kidney disease and risk of incident peripher c2017 Sep a718-7280 v53 a

BACKGROUND: Some evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease.

METHODS: In this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics.

FINDINGS: We analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m2, adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m2 and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m2. Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR <30 mL/min per 1·73 m2 plus ACR ≥300 mg/g or dipstick proteinuria 2+ or higher vs eGFR ≥90 mL/min per 1·73 m2 plus ACR <10 mg/g or dipstick proteinuria negative). Both eGFR and ACR significantly improved peripheral artery disease risk discrimination beyond traditional predictors, with a substantial improvement prediction of amputation with ACR (difference in c-statistic 0·058, 95% CI 0·045-0·070). Patterns were consistent across clinical subgroups.

INTERPRETATION: Even mild-to-moderate chronic kidney disease conferred increased risk of incident peripheral artery disease, with a strong association between albuminuria and amputation. Clinical attention should be paid to the development of peripheral artery disease symptoms and signs in people with any stage of chronic kidney disease.

FUNDING: American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

1 aMatsushita, Kunihiro1 aBallew, Shoshana, H1 aCoresh, Josef1 aArima, Hisatomi1 aArnlöv, Johan1 aCirillo, Massimo1 aEbert, Natalie1 aHiramoto, Jade, S1 aKimm, Heejin1 aShlipak, Michael, G1 aVisseren, Frank, L J1 aGansevoort, Ron, T1 aKovesdy, Csaba, P1 aShalev, Varda1 aWoodward, Mark1 aKronenberg, Florian1 aChronic Kidney Disease Prognosis Consortium uhttps://chs-nhlbi.org/node/7575