Review
Copyright ©The Author(s) 2020.
World J Diabetes. Aug 15, 2020; 11(8): 322-350
Published online Aug 15, 2020. doi: 10.4239/wjd.v11.i8.322
Table 1 Classification of cardiorenal syndromes
TypePrimary and secondary organs and processes affected in the syndromes
PrimarySecondary
Type 1Cardiac impairment, acuteRenal impairment
Type 2Cardiac impairment, chronicRenal impairment
Type 3Renal impairment, acuteCardiac impairment
Type 4Renal impairment, chronicCardiac impairment
Type 5Systemic conditionCardiac and renal impairment
Table 2 The range of adiposity - classifications and thresholds for white individuals
General adiposity (SAT and VAT) BMI, kg/m2Thresholds and classification
< 24.9Normal
25-29.9Overweight
30-34.9Class I
35-39.9Class II
≥ 40Class III
Central adiposity (VA)Thresholds
WCM: ≥ 94 cm, W: ≥ 80 cm
Thresholds depend on BMI and ethnicity
Waist-to-height ratio (index of central obesity)> 50 yr: ≥ 0.6, < 40 yr: ≥ 0.5
Waist-to-hip ratioM: ≥ 0.9, W: ≥ 0.85
Neck circumferenceM: ≥ 40.5 cm W: ≥ 34.2 cm
Sagittal abdominal diameter> 30 cm correlates with CV risk
Visceral adiposity index[189]The formula for M and W depends on WC,BMI, TG and HDL-cholesterol
Ectopic and parenchymal adiposity
Liver, epicardial and renal fat tissueContinuous variable, MRI or TC
Table 3 Major studies on the effect of bariatric surgery in heart failure outcomes
Year, countryParticipantsSurgical/ControlFollow-up Surgical proceduresHF typeHF and LV outcomes
Alpert et al[190]1985, United States62 vs none4.3 ± 0.3 moNAA decrease in LV dimensions
Surgical gastric restriction.(↑ LVS, ↑ LVpW)Lower mean blood pressure
Ramani et al[131]2008, United States12 vs 101 yrHFrEF (treated)Lower hospital readmission
Mostly LRYGBLVEF improved
NYHA improved
Miranda et al[130]2013, United States13 vs 64.3 yrHFrEF 77%Better Quality of life
Mostly RYGBHFpEF 23%Better functional capacity
Less leg edema
Vest et al[127]2016, United States38 vs 2588 non surgical obese2.6 yrHFrEFImprovement in LVEF; 28% improved; LVEF > 10% vs < 1% control
RYGB, AGB, SG
Shimada et al[126]2016, United States524 vs none2 yrNALower rate of HF exacerbations (ED visits), 1 to 2 yr after surgery
Lower rate of hospitalizations
Berger et al[191]2018, Switzerland676 (meta-analysis of surgery vs conventional treatment)NANAHR for the incidence of HF in MO without pre-existing HF 0.44 (0.36, 0.55) vs conventional treatment
Reduced ED visits and readmission
Increase left ventricular ejection
Improve the quality of life and symptoms
Table 4 Major studies onf the effect of bariatric surgery on renal outcomes
AuthorsYear, countryFollow upPatientsSurgical/controlSurgical procedureDiabetes, CVD, RDOutcomes
Serra et al[192]2015, Spain (76 ± 42 mo)92 vs noneGBD2: 14%No WRF
Renal biopsyGlomerulopathy 75%A decrease in creatinine and albuminuria
No progression (not related to glomerular lesions)
Neff et al[142]201, France (1 and 5 yr)190 vs 271RYGB vsD2: 39%. CVD:Improvement in eGFR in both procedures
LAGB28%. CKD: 4%
RYGB better in remission of hypertension
RYGB better in diabetes
Nehus et al[143]2017, United States242 vs none3 yrD2: 12.6%eGFR increased by 3.9 mL/min per 1.73 m2 for each 10-unit loss of BMI.
RYGB 66.5%Albuminuria: 17%
SG: 27.7%A decrease in ACR
AGB: 5.8%
Wakamatsu[141]2018, Japan254LSG 24D2: 51%Improvement of eGFRcys in mild CKD (eGFRcys ≥ 60 mL/min per 1.73 m2)
LSG-DJB 94
LRYGB 26
LAGB 10
NS: eGFRcys in moderate CKD (< 60 mL/min per 1.73 m2)
Solini et al[138]2019, Italy25 vs none1 yrNo D2. No HTAImprovement in mGFR
RYGBImprovement in a renal resistive index and correlates with mGFR
Lowers carotid intima-media thickness
Inge et al[144]2019, United StatesAdoles vs adults5 yrD2: 14% vs 31%HTA and D2 remissions are higher in adolescents than in adults. Rate of death (NS)
161 vs 396RYGBHTA: 30% vs 61%
Table 5 Recent major clinical trials of MRA in cardiorenal syndrome and their relationship with adiposity
Trialn (follow-up)BMI > 30 %eGFR % < 60 mL/minCVD(%) vs HF(%)DM2CV and RO (HR, significant)
EMPHASIS-HF[159] (eplerenone vs PBO)2737 (21 mo)27%33%70% (IHD)31%CVO1,2,3,4,5
HFrEF (NYHAII)RO: NS
High WC: Greater benefit of eplerenone[163]
TOPCAT[96] (spironolactone vs PBO)3445 (3.3 yr)50%39%59%(IHD)32%CVO4
HFpEF (NYHAII-IV)
TOPCAT post hoc[193] (BMI&NP categories)997 (3.3 yr)NRNRNRNRHigh BMI/high NP1,4,5
High NP5
TOPCAT post hoc[166] (eGFR categories)1767 (3.3 yr)70%53.4%MI (20.3%)44.5%AE increased with declining eGFR eGFR ≥ 60 vs eGFR ≤ 451,2,4,5
FIDELIO-DKD[170] (finerenone vs PBO)5734 (< 48 mo)58%87%45.9% & 7.5 (HFpEF)100%Outcomes expected in 2020 (composite RO and secondary endpoints CV )
FIGARO-DKD[171] (finerenone vs PBO)7437 (< 53 mo)60%38%44.3% & 7.6% (HFpEF)100%Outcomes expected in 2021 (composite RO and secondary endpoints CV )
AMBER[167] (patiromer vs PBO)295 (3 mo)NR100%19.3% (MI) & 45% (HF)49.1%Les hyperkaliemia
Less Spironolactone withdrawal
Table 6 Major sodium-glucose cotransporter 2 inhibitors clinical trials and cardiorenal outcomes
Trialn (follow-up)BMI > 30eGFR < 60 mL/min per 1.73 m2CVD and HFDiabetesCVO and RO (HR; significant)
EMPA-REG[175] (empagliflozin vs PBO)7020 (3.1 yr)51%25.9%99.2% and 10.1%About 100%CVO1,2,3,4 RO6,7,8,9,10
CANVAS[172] (canagliflozin vs PBO)10142 (2.4 yr)59%20,1%65.6% and 14.4%About 100%CVO1,3 RO6,7,8,9
DECLARE-TIMI[174] (dapagliflozin vs PBO)17160 (4.2 yr)60%7.4%40.6% and 10%About 100%CVO1,3 RO6,7
CREDENCE[173] (canaglifozin vs PBO)4401 (2.6 yr)54.4%60%50.4% and 15%52%RO6,7,8,9 CVO1,2,3,4
DAPA-HF[176] (dapagliflozin vs PBO)2373 (18.2 mo)35%26.1%55.5% (IHD) and 100% (HFrEF)41%CVO1,2,3 RO: NS HFrEF: Better dapagliflozin
DAPA-CKD[194] (dapagliflozina vs PBO)4304 (NA)NAAbout 90%NANon-DM: ≥ 30%Outcomes expected in 2020 (composite renal and secondary CV endpoints)
EMPEROR-Preserved[195] (empagliflozin vs PBO)5988 (NA)NANA (eGFR ≥ 20)HFpEF (100%)NAOutcomes expected late in 2020 (composite CV, HF and secondary R endpoints)
EMPEROR-Reduced[196] (empaglifozin vs PBO)3730 (NA)NANA (eGFR ≥ 20)HFrEF (100%)NAOutcomes expected late in 2020 (composite CV, HF and secondary RO)
Table 7 Major GLP-1 clinical trials and cardiorenal outcomes
Trialn(follow-up)BMI >30 %eGFR %< 60 mL/minCVD% vsHF%DM2CVO & RO (HR, significant)
LEADER[197] (liraglutide vs PBO)9340 (3.8 yr)61%23.1%81% vs 14% (NYHAII-III)ALLCVO12
RO6: Reduction in progression to Macroalbuminuria
FIGHT[183] (liraglutide vs PBO)300 (180 d)50%40%100% vs 100%HFrEF (NYHAIII-IV)59%CVO:NS
RO: Increase in cystatin C in the liraglutide group
SUSTAIN-6[198] (Semaglutide vs PBO)3297 (2.1 yr)64%28.5%83% vs 24%ALLCVO1245
RO6: Reduction in progression to macroalbuminuria
EXSCEL[199] (exenatide-ER vs PBO)14752 (3.2 yr)63%21.6%73% vs 16%ALLCVO: NS; RO: NA
HARMONY OUTCOMES[200] (Albiglutide vs PBO)9463 (1.6 yr)62%NA100% vs 20%ALLCVO13; RO: NA
REWIND[201] (dulaglutide vs PBO)9901 (5.4 yr)46%22%31.5% vs 9% (NYHAII-III)ALLCVO14
RO6: Reduction in Macroalbuminuria and eGFR (dulaglutide group)
PIONEER 6[202]3183 (1.33 yr)60%26.9%%85% vs 12%ALLCVO12 for noninferiority