Long-term prognostic role of adiponectin in stable coronary artery disease: A meta-analysis of prospective studies

Table 1 Newcastle Ottawa Scale for critical appraisal of included studies

Criteria		Study 1	Study 2	Study 3	Study 4	Study 5
Selection
Representativeness of the exposed cohort	Were the included patient’s representative of the population with stable CAD	Yes	Yes	Yes	Yes	Yes
Selection of the non-exposed cohort	Were appropriate comparison groups selected to evaluate the association between adiponectin and outcomes in stable CAD patients	-	-	Yes	-	Yes
Ascertainment of exposure	Were adiponectin levels accurately measured and defined in the studies	Yes	Yes	Yes	Yes	Yes
Demonstration that outcome of interest was not present at the start of the study	Were patients with pre-existing conditions or adverse outcomes excluded or adequately accounted for at baseline	Yes	Yes	Yes	Yes	Yes
Comparability
Comparability of cohorts on the basis of the design or analysis	Did the studies control for only for main factor or all potential confounding factors or perform appropriate adjustments when examining the association between adiponectin and outcomes in stable CAD patients	Yes	Yes	Yes	Yes	Yes
Outcome
Assessment of outcome	Were the outcomes of interest (e.g., cardiovascular events, mortality) clearly defined and assessed using standardized criteria across the studies	Yes	Yes	Yes	Yes	Yes
Was follow-up long enough for outcomes to occur	Did the studies have a sufficient follow-up period to capture the occurrence of outcomes in stable CAD patients with adiponectin levels	Yes	Yes	Yes	Yes	Yes
Adequacy of follow-up of cohorts	Did the studies achieve a high follow-up rate for both the exposed and non-exposed cohorts throughout the follow-up period	-	-	Yes	-	Yes

CAD: Coronary artery disease.

Table 2 Characteristics of study population, n (%)

Ref.	Location	Study design	Cohort	Sample size	Mean/median age (years)	Median follow-up (years)	Male participants	Hypertension	Hyperlipidemia	DM	Obesity (BMI > 25 kg/m2)	History of myocardial infarction	Smoking	Adiponectin cut offs	Outcomes reported (ACM, MACE)	Multivariable regression analysis was adjusted for which variables/confounders
Marino et al[15], 2018	Netherlands	Prospective	Total: 570, ACS: 309, SAP: 261	261	N/A	1	203 (77.8)	161(61.70)	Hypercholesterolemia: 180 (69)	59 (22.60)	N/A	N/A	49 (18.8)	In ACS patients-median IQR: 2.9 (1.8-4.1 μg/mL) μg/mL. In SAP patients-median IQR: 2.9 (1.9-3.9 μg/mL) μg/mL	ACM adjusted OR/HR = 8.48 (0.92-78.03), MACE adjusted OR/HR = 1.33 (0.41-4.28)	ACS and SAP-adjusted for age, gender, diabetes, hypertension, and CRP. Additionally, adjusted for indication for coronary angiography in the total cohort
Pratesi et al[16], 2016	Italy	Prospective	Stable CAD	138	69.3 ± 10.4	3.8	122 (89.7)	98 (71)	99 (71.70)	61 (42.20)	Mean level of BMI was 26.8 kg/m2 ± 4.1 kg/m2	114 (82.60)	91 (65.94)	13.2 ng/mL	ACM adjusted OR/HR = 11.31 (2.89-44.28)	Model 1 (ACM), age, gender, BMI, Inflammatory Disease Score, previous percutaneous transluminal coronary angioplasty, atrial fibrillation, peripheral artery disease, NYHA class, EF, hemoglobin, NT-proBNP, eGFR. Model 2 (cardiovascular hospitalisation rate): age, gender, BMI, smoking, NYHA class, hemoglobin, NT-proBNP, EF
Hascoet et al[14], 2013	France	Prospective	Stable CAD	715	60.2 ± 8	8.1	715 (100)	44.60%	64.90%	24.8%	N/A	N/A	82.50%	9.1 μg/mL	ACM adjusted OR/HR = 1.71 (1.16-2.52)	Diabetes mellitus, dyslipidaemia, and hypertension, systolic blood pressure, resting heart rate, tobacco consumption, hsCRP, HDL cholesterol, lipoprotein (a), ankle-arm index, and physical activity
Beatty et al[13], 2012	United States	Prospective	Stable ischemic heart disease	981	64 ± 10.5, 64.9 ± 10.2, 67.6 ± 10.9, 70.5 ± 11.2	7.1	800 (81.5)	691	N/A	259	N/A	N/A	N/A	Lowest detectable: 145.4 pg/mL. Median: 21.3 μg/mL	ACM adjusted OR/HR = 1.77 (1.12-2.67)	Model 1 adjusts for Demographics (age, sex, race). Model 2 adjusts for model 1 + clinical risk factors (diabetes, eGFR, beta-blocker, aspirin, statin). Model 3 adjusts for model 2 + metabolic markers (BMI, hemogloblin A1c, insulin, glucose, non-HDL cholesterol, HDL, triglycerides). Model 4 adjusts for model 3 + measures of baseline cardiac disease severity (left ventricle ejection fraction, diastolic dysfunction, inducible ischemia, log CRP, log NT-proBNP)
Schnabel et al[17], 2008	Germany	Prospective	Total: 1890; stable CAD: 1130; ACS: 760	1130	63	2.5	906 (80.2)	896	Total cholesterol: 194; HDL: 48; low density lipoprotein: 121; triglycerides: 129	DM: None or diet: 929; oral: 103; insulin: 98	N/A	N/A	No: 413; past: 523; present: 194	Not mentioned but concentrations were similar in patients presenting with SAP [9.03 μg/mL (6.7-13.45 μg/mL)] or ACS [(9.19 μg/mL (6.72-13.15 μg/mL)]	MACE adjusted OR/HR = 1.04 (1.008-1.062)	Model 1, univariate analysis. Model 2 is adjusted for age, sex, BMI, hypertension, diabetes mellitus, smoking, status, HDL cholesterol family history, ACS (only for total population). Model 3 is adjusted for age, sex, BMI, hypertension, diabetes mellitus, smoking, status, family history, ACS, statins, and beta blocker. Model 4 is adjusted for age, sex, BMI, hypertension, diabetes mellitus, smoking, status, family history, statins and beta blocker, BNP, and CRP

ACM: All cause mortality; ACS: Acute coronary syndrome; BMI: Body mass index; CAD: Coronary artery disease; CRP: C-reactive protein; DM: Diabetes mellitus; EF: Ejection fraction; EGFR: Estimated glomerular filtration rate; HDL: High density lipoprotein; HR: Hazard ratio; NT-proBNP: N-terminal pro B-type Natriuretic Peptide; NYHA: New York Heart Association; IQR: Interquartile range; MACE: Major adverse cardiovascular events; N/A: Not available; OR: Odds ratio; SAP: Stable angina pectoris.