Table 2.

Studies assessing N-terminal pro-brain natriuretic peptide (NT-proBNP).

Citation	Type of Study	Quality of Study	Population	CV Outcomes	Length of Follow-Up	Main Results
James A. de Lemos, et al. Circulation. 2018 [19].	Cohort (Prospective study)	Good	A total of 6621 participants aged 45–84 years from the MESA study (these participants were excluded from the current analysis) and 2202 participants aged 30–65 years from the DHS study.	Non-fatal and fatal defined as ICD-10 a codes, I00-I99 (diseases of the circulatory system), including acute rheumatic fever, chronic rheumatic heart diseases, hypertensive diseases, ischemic heart diseases, cerebrovascular diseases, etc., were included.	Over a median follow-up period of 10.3 years.	In the DHS study, 179 global cardiovascular disease (CVD) events occurred, including 96 ASCVD b events. NT-ProBNP in continuous analysis and categorical analysis (≥100 pg/mL c) after multivariable adjustment for risk factors had hazard ratio (HR) 1.19 (confidence interval (CI) 95%: 1.01–1.41) and 1.88 (1.29–2.75) for CV endpoint.
Hugh Tunstall-Pedoe, et al. Journal American Heart Association (AHA). 2017 [20].	Cohort (Prospective study)	Good	A total of 15,737 participants from the Scottish Heart Health Extended Cohort (SHHEC) with mean age of 49 (standard deviation (SD) 8.3) years.	Coronary heart disease (CHD) was defined as ICD 9 codes 410 to 414 and ICD 10 I20 to I25, while peripheral artery disease (PAD) was defined as ICD 9 440.2, 443.9, 250.6 and ICD 10 I70.2, I73.9, E10.5, E11.5, E12.5, E13.5, E14.5.	A mean follow-up period of 19.9 years.	A total of 3098 CHD events and 499 PAD events occurred. NT-proBNP showed a HR 1.21 (CI 95%:1.16–1.27).
Paul Welsh, et al. European Heart Journal. 2012 [29].	Cohort (Prospective study)	Good	A total of 4128 moderately hypercholesterolaemic men included in the clean CVD cohort from the WOSCOPS clinical trial were included in the current analysis. Clean CVD cohort: patients with positive Rose angina, stroke/TIA d, ECG e abnormalities, claudication and history of another type of vascular disease were excluded.	Death from or hospitalization for CHD, non-fatal MI, and fatal or non-fatal stroke.	A median follow-up period of 14.7 years.	A total of 1357 CVD events were recorded. HRs 1 SD increase in log NT-proBNP for all CVD events was 1.20 (CI 95%: 1.13–1.27, p < 0.001), but was not significant for CHD events after adjusts. However, when the fatal events were analyzed both CVD deaths and CHD deaths had significant differences after the adjustments, HRs 1.29 (1.11–1.48, p < 0.001) and 1.22 (1.03–1.45, p < 0.02) respectively.
MH Olsen, et al. Journal of Human Hypertension. 2009 [39].	Cohort (Prospective study)	Fair	A total of 1988 healthy subjects were included after the exclusion of 472 subjects from the baseline study with known diabetes, prior myocardial infarction or stroke. These healthy subjects were classified using HeartScore as high risk (559) and low-moderate risk (1429), depending on the expected 10-year risk of CV death above or below 5%.	Cardiovascular death, non-fatal myocardial infarction or stroke.	A follow-up period of 9.5 years.	A total of 204 cardiovascular endpoints occurred during follow-up. In univariate Cox-regression analyses for NT-proBNP, HRs for composites of CV endpoint and CV death in low-moderate risk subjects was 1.1 (CI 95%: 0.6–2.1) and 2.1 (CI 95%: 0.6–6.9), which was not significant, and in high-risk subjects was 2.6 (CI 95%: 1.6–4.3) p < 0.001 and 4.7 (CI 95%: 2.5–9.1) p < 0.001 respectively.

^a international classification disease (ICD-10), ^b atherosclerotic cardiovascular disease (ASCVD), ^c picogram/milliliter (pg/mL), ^d transient ischemic attack (TIA), ^e electrocardiogram (ECG).