Table 2.
Major findings from clinical studies.
| Disease | Metabolites | Major findings | Study design and size | Reference |
|---|---|---|---|---|
| AF | FFA | FFA levels were associated with the development of AF. | Prospective: 182 patients | Jung, Y., et al.30 |
| Diabetes | NEFA | Plasma NEFA was positively association with incident diabetes. | Prospective: 3740 Cardiovascular Health Study participants | Djousse, L., et al.31 |
| CHD | FFA | High FFA might identify patients with stable CHD with worse prognoses. | Prospective: 1206 participants in 3-weeks inpatient rehabilitation programs | Breitling, L.P., et al.32 |
| HF | FFA | Plasma FFA was associated with a higher risk of HF in older adults. | Prospective: 4248 men and women free of HF at baseline and > 65 years old | Djousse, L., et al.33 |
| HF | FFA | A long-term reduction in FFAs with acipimox did not change cardiac function in patients with HF. | Randomized, double-blind and crossover: 24 HF patients with ischemic heart disease | Halbirk, M., et al.35 |
| Heart failure caused by IDCM | FFA | Acutely decreased serum FFA depressed cardiac work. | Randomized and controlled: 18 fasting nondiabetic patients and 8 matched healthy controls | Tuunanen, H., et al.36 |
| Obese HFpEF | UFA | Consumption of UFA was linked to better cardiorespiratory fitness. | Randomized: 23 obese HFpEF patients | Carbone, S., et al.39 |
| Incident congestive heart failure | LCMUFA | LCMUFAs had possible cardiotoxicity in humans. | Retrospective: 3694 older adults and 3577 middle-aged adults | Imamura, F., et al.40 |
| Non-ST‐segmentelevation‐acute coronary syndrome | ω‐3 PUFA | Plasma long‐chain ω3‐PUFAs were inversely associated with lower odds of sudden cardiac death. | Randomized and controlled: 203 patients with cardiovascular death, 325 with myocardial infarction, 271 with ventricular tachycardia, and 161 with atrial fibrillation, and a random sample of 1612 event‐free subjects as controls | Zelniker, T.A., et al.42 |
| CVD | ω‐3 PUFA | Higher levels of blood ω-3 PUFAs were associated with a lower risk of cardiovascular disease death. | Prospective: 42 466 individuals | Harris, W.S., et al.43 |
| CVD | ω‐3 PUFA | ω-3 PUFAs could be predictors of cardiovascular risk. | Randomized and controlled: 356 individuals who are 30 to 74 years, with at least one cardiovascular risk factor, and no previous cardiovascular events | Goncalinho, G.H.F., et al.44 |
| HF | EPA | Higher plasma EPA was associated with reduced risk for HF. | Prospective: a total of 6562 participants | Block, R.C., et al.46 |
| Cardiomyopathy | DHA, EPA | Decreased DHA and EPA levels were associated with reduced LVEF. | Randomized and controlled: 30 patients | Alter, P., et al.47 |
| ADHF | TyG | The elevated plasma TyG was independently associated with poor prognosis in patients with ADHF. | Retrospective: a total of 932 hospitalized patients with ADHF | Huang, R., et al.49 |
| ADHF | ω‐6 PUFA | Lower ω-6 PUFA levels might be useful for identifying higher risk ADHF patients. | Prospective: 685 consecutive ADHF patients | Nagai, T., et al.51 |
| ADHF | AA | The AA score predicted 1-year death in patients with ADHF. | Retrospective: discovery cohort n = 419; validation cohort n = 386 | Ma, K., et al.52 |
| HF | EPA, AA | The ratio of EPA to AA was an independent predictor of cardiac mortality in patients with HF. | Randomized and controlled: a total of 577 consecutive patients | Watanabe, S., et al.53 |
| Congestive heart failure | SCFA | Altered SCFA concentrations were additional intestinal dysfunctions in patients with congestive heart failure. | Dual stable tracer: 14 clinical patients | Kirschner, S.K., et al.57 |
| HF | LCAC | Increased circulating LCACs were associated with adverse effects of HF. | Randomized and controlled: 72 control subjects and 68 HF patients | Ruiz, M., et al.65 |
| HF | LCAC | The plasma LCACs were substantially higher as the HF developed. | Randomized and controlled: 515 participants | Cheng, M.L., et al.66 |
| HFpEF, HFrEF | LCAC | LCACs were independently associated with HF and differentially elevated in HFpEF and HFrEF. | Randomized and controlled: HFpEF cases (n = 282), HFrEF controls (n = 279), no-HF controls (n = 191) | |
| Hunter, W.G., et al.67 | ||||
| HFpEF, HFrEF | AC, FC | The ratio of AC/FC could identify high risk HF patients, especially those with HFpEF. | Prospective: 168 HF patients | Yoshihisa, A., et al.68 |
| CHF | LCAC | Increased LCACs were independently associated with adverse clinical outcomes and decreased after circulatory support. | Randomized and controlled: 453 chronic systolic HF patients | Ahmad, T., et al.69 |
| HF | Amino acids, LCAC | Circulating amino acids and LCACs were associated with progression of HF. | Randomized and controlled: a total of 96 HF cases and 97 controls | Liu, C., et al.70 |
| HF, DM | LCAC | LCACs were differentially associated with clinical outcomes in HF patients with or without DM. | Randomized and controlled: 664 participants | Truby, L.K., et al.71 |
| T2DM | LCAC | Elevated LCACs were associated with CVD risk in T2DM. | Cross-sectional: 741 patients with T2DM | Zhao, S., et al.73 |
| HF | Triglycerides | Stepwise higher concentrations of nonfasting triglycerides were associated with stepwise higher risk of heart failure. | Prospective: 113 554 individuals | Varbo, A. and B.G.77 |
| CAD, ACS | Ceramides | Ceramides were significant predictors of CV death both in patients with stable CAD and ACS. | Prospective: 160 stable CAD patients | Laaksonen, R., et al.79 |
| Major adverse cardiovascular events | Ceramides | Ceramides were associated with the risk of major adverse cardiovascular events. | Prospective: 8101 apparently healthy individuals. | Havulinna, A.S., et al.81 |
| HF | Ceramide, Sphingomyelins | Plasma levels of ceramide and sphingomyelins were associated with risk of heart failure. | Prospective: 1179 cases of incident heart failure | Lemaitre, R.N., et al.85 |
| HF | VLSFA | Higher levels of circulating VLSFAs were associated with lower risk of incident HF in older adults. | Prospective: 1304 incident heart failure events | Lemaitre, R.N., et al.88 |
| HF | SFA | Plasma phospholipid SFAs were not associated with HF. | Prospective nested matched case–control: 788 cases of incident HF and 788 controls | Matsumoto, C., et al.90 |
| HF | Glucose | Admission glucose levels had no significant association with mortality in patients hospitalized with other cardiovascular conditions. | Retrospective: 50 532 elderly patients | Kosiborod, M., et al.93 |
| HF | FPG | FPG was positively, continuously, and independently associated with risk for HF. | Prospective: 1740 men aged 42–61 years | Khan, H., et al.95 |
| HF, diabetes | FPG | Impaired FPG and diabetes were predictors of death in patients with HF. | Prospective: 1791 military veterans | Gotsman, I., et al.101 |
| Congestive heart failure | Ketone bodies | Blood ketone bodies were increased in accordance with the severity of cardiac dysfunction in CHF. | Randomized and controlled: 45 patients with chronic CHF and 14 control subjects free of CHF | Lommi, J., et al.114 |
| HFrEF | 3-OHB | High plasma concentrations of 3-OHB were associated with an increased risk of HFrEF, particularly in women. | Prospective: 227 subjects (137 with HFrEF, 90 with HFpEF) | Flores-Guerrero, J.L., et al.115 |
| CHF | 3-OHB | Increased 3-OHB after treatment with empagliflozin had negative effects on vascular function in patients with stable CHF ketone bodies. | Prospective, double blind, placebo controlled and parallel-group single centre: 75 patients | Pietschner, R., et al.119 |
| HF | 277 metabolites | Comprehensive quantification of fuel use by the failing and nonfailing human heart | Randomized and controlled: 110 patients | Murashige, D., et al.124 |
| T2DM | BCAAs | Circulating levels of BCAAs were positively associated with incident HF in patients with T2DM. | Prospective: 2139 T2D patients free of cardiovascular-renal diseases | Lim, L.L., et al.126 |
| STEMI with AHF | BCAAs | Increased plasma BCAA levels were associated with long-term adverse cardiovascular events in patients with STEMI and AHF. | Prospective: 138 patients with STEMI and AHF | Du, X., et al.127 |
| HF | Leucine, valine and acylcarnitines | A profile that consisted of leucine, valine and acylcarnitines was a predictor of mortality. | Randomized and controlled: 1032 HFrEF patients | Lanfear, D.E., et al.128 |
| Asymptomatic left ventricular diastolic dysfunction | BCAAs | Higher BCAAs could maintain diastolic left ventricular function in individuals without structural heart disease. | Prospective: 570 randomly recruited people | Zhang, Z.-Y., et al.132 |
| HF | Two metabolic panels | The profile of metabolites provided better prognostic value compared to conventional biomarkers. | Randomized and controlled: 515 participants | Cheng, M.L., et al.66 |
| HF | Phenylalanine | Phenylalanine was a novel predictor for incident heart failure hospitalization in the elderly | Double-blind, randomised, placebo-controlled trial: the Elderly (n = 12 671) | Delles, C., et al.133 |
| HFpEF, HFrEF | Amino acids, phospholipids and acylcarnitines | Higher levels of hydroxyproline and symmetric dimethyl arginine, alanine, cystine, and kynurenine, and lower levels of serine and arginine were found in the plasma of HFpEF patients compared to HFrEF patients. | Randomized and controlled: HFpEF (n = 46) and HFrEF (n = 75) patients | Hage, C., et al.134 |
| HF and reduced muscle endurance | Kynurenine | kynurenine might be a potential biomarker for patients with HF and reduced muscle endurance. | Prospective: 18 HFrEF, 17 HFpEF, and 20 healthy controls | Bekfani, T., et al.135 |
| AHF | Lactate | Infusion of half-molar sodium lactate improved cardiac performance in AHF patients without any detrimental effects on organ function. | Prospective, randomized, controlled and open-label: 40 patients | Nalos, M., et al.139 |
| AHF | Lactate | An elevated blood lactate on admission was common in AHF patients. | Prospective: 237 patients with AHF | Zymlinski, R., et al.142 |
AF, Atrial fibrillation; FFA, Free fatty acid; NEFA, Nonesterified fatty acids; CHD, Coronary heart disease; HF, Heart failure; IDCM, Idiopathic dilated cardiomyopathy; HFpEF, Heart failure with preserved ejection fraction; UFA, Unsaturated fatty acid; LCMUFA, Long-chain monounsaturated fatty acid; ω-3 PUFA, Omega-3 polyunsaturated fatty acid; EPA, Eicosapentaenoic acid; DHA, Docosahexaenoic acid; ADHF, Acute decompensated heart failure; TyG, The triglyceride glucose; ω-6 PUFA, Omega-6 polyunsaturated fatty acid; AA, Arachidonic acid; SCFA, Short-chain fatty acid; LCAC, Long-chain acylcarnitine; AC, Acylcarnitine; FC, Free carnitine; HFrEF, Heart failure with preserved ejection fraction; DCM, Dilated cardiomyopathy; VHD, valvular heart disease; DM, Diabetes mellitus; T2DM, Type 2 diabetes mellitus; CAD, Coronary artery disease; ACS, Acute coronary syndromes; VLSFA, Very-long-chain saturated fatty acid; SFA, Saturated fatty acids; FPG, Fasting plasma glucose; 3-OHB, 3-hydroxybutyrate; CHF, Chronic heart failure; BCAAs, Branched-chain amino acids; STEMI, ST-segment elevation myocardial infarction; AHF, Acute heart failure.