Search

Inhibitors of sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown effective glucose-lowering effects associated with improved clinical outcomes in diabetic patients and heart failure patients. As SGLT2 inhibitors can increase phosphate levels, they can also modulate FGF-23 production, a hormone directly involved in regulation of bone and mineral metabolism, but also a strong predictor of adverse cardiovascular events. We therefore discuss the relevance of FGF-23 as a companion testing of SGLT2 treatment, in addition to standard clinical biology tests.

Natriuretic peptides are widely used in clinical practice as cardiac markers for early diagnosis, prognosis and for the monitoring of treatment efficiency of heart Failure (HF). According to the clinical relevance of natriuretic peptides testing, it is important to assess the performances of novel platform for testing. Our study showed the overall good performances of a new NT-proBNP ABEI-based automated immunoassay.

BACKGROUND AND AIMS: Non-alcoholic fatty liver (FL) is comorbid with obesity, metabolic syndrome and type 2 diabetes. Atherogenic dyslipidaemia (AD), frequent in FL, is associated with risk of micro- and macrovascular complications. Given the paradoxical ocular protection of FL in T2DM, we studied how FL modulates micro- and macrovascular complications as a function of AD. METHODS: Cross-sectional factorial analysis of 744 diabetic patients in whom FL, identified by ultrasonography, was present in 68%. AD, defined by low HDL-C plus elevated TG, was present in 45%. Four groups were analysed as regards cardiometabolic features, micro-/macroangiopathies, cataract and ocular hypertonia: FL[-]AD[-] (n = 171); FL[-]AD[+] (n = 66); FL[+]AD[-] (n = 235); and FL[+]AD[+] (n = 272). RESULTS: Age, gender and glycemic control were similar across groups. Prevalence of overall macroangiopathy and coronary artery disease were higher in patients with AD, irrespective of FL. Overall macroangiopathy was higher, by 64% in FL[-]AD[+] and by 38% in FL[+]AD[+]. Coronary artery disease was higher, by 128%, in FL[-]AD[+], and by 67%, in FL[+]AD[+]. (Micro)albuminuria was more frequent (+55%) in FL[-] AD[+] compared to FL[-] AD[-]. Retinopathy prevalence was 35% in FL[-], unaffected by AD. Retinopathy frequency was much lower in FL[+], irrespective of AD, decreased by -47% in FL[+]AD[-] and -32% in FL[+]AD[+] (vs. FL[-]AD[-]). Ocular hypertonia was present in 13%, and its prevalence was also markedly lower (-31%) in FL[+]. Cataract frequency was 29%, also lesser in FL[+] (24% vs. 39%), irrespective of AD. CONCLUSIONS: Multi-level eye protection in diabetes is linked to non-alcoholic fatty liver independently of atherogenic dyslipidemia.

BACKGROUND AND AIMS: In type 2 diabetes mellitus (T2DM), sexual dimorphisms modulate the natural histories of hyperglycemia, anthropophysical/cardiometabolic phenotype, and susceptibility to chronic micro and macrovascular complications. The purpose of this work was to revisit known or new dimorphisms within a multiethnic cohort. METHODS: Among 1238 T2DM patients, men (63%) were compared to women (37%), including leading ethnicities: Whites (67.4%; 542 men; 293 women); Maghrebians (9.4%; 62 men; 54 women); and Blacks (12.5%; 92 men; 63 women). RESULTS: Age, BMI, diabetes duration, insulin sensitivity, B-cell function loss, HbA1c, and hyperglycemia index were similar in both genders. All-cause microangiopathy and cerebrovascular disease did not differ between sexes. Women had significantly more retinopathy (27% vs. 21%) and men more microalbuminuria (25% vs. 19%), all-cause macroangiopathy (40% vs. 26%), CAD (29% vs. 17%) and PAD (11% vs. 6%). Among Blacks, sexual dimorphism in terms of retinopathy was more pronounced (24% in women vs. 11%), while there was no sexual dimorphism in all-cause macroangiopathy, CAD or PAD. B-cell function loss was faster among North African men (+15%), who also had more hepatic steatosis (+27%) than women. CONCLUSIONS: T2DM abolishes the CV protection provided by the female gender in Blacks. In White women, the loss of CV protection in diabetes is limited to cerebrovascular disease. In Black women, a markedly increased risk of retinopathy is present, despite glycemic exposure similat to men. Sexual dimorphisms do not affect glucose homeostasis and metabolic control in all ethnicities, except for lesser B-cell function loss in Maghrebian women.

Objectives: To determine concentrations of heart-type fatty acid-binding protein (HFABP) in patients with heart failure with reduced ejection fraction (HFrEF) and its potential value for prognostic assessment. Methods: Circulating levels of HFABP were measured with an automated chemiluminescent immunoassay in 25 healthy volunteers and 60 HFrEF patients. Results: Concentrations of HFABP were significantly increased in heart failure patients in comparison to healthy volunteers. HFABP levels were significantly correlated to New York Heart Association classes and to established biomarkers of cardiac dysfunction and remodeling (amino-terminal pro-B-type natriuretic peptide [NT-proBNP], fibroblast growth factor 23, and galectin-3). HFABP concentrations were also predictive of cardiovascular (CV) death and combination with NT-proBNP might be synergistic for risk assessment. Conclusions: HFABP levels are increased in HFrEF patients, related to adverse CV outcomes, and might assist physicians for patient's management. © 2021 Damien Gruson et al., published by De Gruyter, Berlin/Boston.

BACKGROUND: New recommendations call for lowering LDL-C < 55 mg/dL and non-HDL-C < 85 mg/dL in very-high cardiovascular risk (VH-CVR) patients with type 2 diabetes (T2DM). This study assessed the proportion of VH-CVR diabetics currently meeting these primary and secondary lipid targets, and which therapies/phenotypes predict combined goals achievement. METHODS: We analysed the cardiometabolic phenotype, use of lipid-modulatind drugs (LMD), pre- and post-LMD lipids levels, and CV complications among 1196 T2DM with high (n = 221; 18%) or VH-CVR (n = 975; 82%). Among the latter, the characteristics of combined lipid goal-achievers (n = 158) were compared to those of non-achievers (n = 817), with subgroup analyses of on-statin patients (n = 732) and those with established CVD taking statins (n = 362). Presence of statin-associated muscle symptoms (SAMS) was also recorded. RESULTS: 75% of VH-CVR patients were on statins. Both LDL-C and non-HDL-C goals were achieved by 16.2% of all VH-CVR, 19.3% of on-statin VH-CVR, and 24.3% of patients with established CVD taking statins. Achieving both targets was associated with high-intensity statins, specifically rosuvastatin, [statin + ezetimibe] combination, lower baseline LDL-C, smaller LDLs, lower TG and lipoprotein(a), and reduced metabolic syndrome frequency. SAMS reporting did not differ between achievers and non-achievers. CONCLUSIONS: More than 80% of patients are above targets. To bridge this gap, apart from treating more LMD-naive/refractory diabetics, one should consider for LDL-C to put most patients on high-intensity statins, more often with ezetimibe and, within statins, to switch preferably to rosuvastatin. As regards non-HDL-C, the off-target patients' phenotype suggests that intensifying lifestyle measures against metabolic syndrome should supplement current therapies.

Handedness is a tangible manifestation of cerebral motor lateralization. It is partly hereditary, it arises early in foetal life, and is modulated by intrauterine, perinatal and epigenetic factors. While the molecular bases of handedness have yet to be formally established, genetic studies have hinted at a polygenic origin partly under the control of molecular mechanisms establishing left–right body asymmetry. A previous report had found that non-right-handed (non-RH) patients with type 2 diabetes mellitus (T2DM) had better insulin sensitivity (IS) than their right-handed (RH) counterparts, which was unrelated to differences in obesity, body composition and physical activity. It was also observed that gastrointestinal intolerance to metformin was associated with a lower prevalence of ischaemic heart disease and with being left-handed (LH), whereas being non-RH was over-represented among metabolically-healthy normal-weight T2DM patients without the metabolic syndrome (MetS). Yet, there are virtually no data on lipids, lipoproteins or apolipoprotein (apo) levels as a function of motor laterality. For this reason, our present analysis was performed to determine whether laterality could modulate lipids/lipoproteins, including lipoprotein(a) [Lp(a)], in DM patients [...]

OBJECTIVES: This study sought to compare the prognostic value of 2-dimensional (2D) right ventricular (RV) speckle tracking (STE) against cardiac magnetic resonance (CMR) RV ejection fraction (EF) and feature tracking (FT) and conventional echocardiographic parameters on overall and cardiovascular (CV) survival in patients with heart failure with reduced EF (HFrEF). BACKGROUND: Prior works showed that RV systolic function predicts prognosis in HFrEF. 2D RVSTE had recently been proposed as new echocardiographic method to evaluate RV dysfunction. METHODS: A total of 266 patients with HFrEF (mean LVEF 23 ± 7%, 60 ± 14 years of age; 29% women) underwent RV function assessment using CMR and 2D echocardiography and were followed for a primary endpoint of overall death and secondary endpoint of CV death. RESULTS: Average CMR-RVEF was 42 ± 15%, average STE RV global longitudinal strain (STE-RVGLS) was -18.0 ± 4.9%, and average CMR-FT-RVGLS was -11.8 ± 4.3%. After a median follow-up of 4.7 years, 102 patients died, 84 of a CV cause. RVEF, FT-RVGLS, tricuspid annulus plane systolic excursion (TAPSE), fractional area change (FAC), and STE-RVGLS were significant univariate predictors of overall and cardiac death. In multivariate Cox regression, age, ischemic etiology, diabetes, New York Heart Association functional class III to IV, and beta-blocker treatment were independent clinical predictors of overall mortality. CMR-RVEF (chi-square to enter = 3.9; p < 0.05), FT-RVGLS (chi-square to enter 3.7; p = 0.05), FAC (chi-square to enter 6.2; p = 0.02), and TAPSE (chi-square to enter = 4.1; p = 0.04) provided additional prognostic value over these baseline parameters, but the additional predictive value of STE-RVGLS (chi-square to enter = 10.8; p < 0.001) was significantly (p < 0.05) higher than the other tests. Additional hazard ratio to predict overall mortality was 2.5 (95% confidence interval [CI]: 1.6 to 3.9) for STE-RVGLS <-19%, 2.15 (95% CI: 1.34 to 3.43) for TAPSE >15 mm, 1.

BACKGROUND: The usefulness of C-reactive protein (CRP) to predict cardiovascular disease (CVD) in type 2 diabetes (T2DM) remains controversial. As many factors linked to obesity can modulate CRP in T2DM, we comprehensively revisited the cardiometabolic phenotype of patients with normal or raised CRP, taking into account the sexual dimorphism of its serum value. METHODS: 1005 T2DM patients (651 males, 354 females; macroangiopathy 38%; coronary artery disease 26%; microangiopathy 47%) were divided depending on whether CRP level was ≤ or >3 mg/L. Thirty percent of men (n = 195) and 39% of women (n = 137) had raised CRP. Their cardiometabolic phenotype and presence of micro- and macrovascular complications were compared to those with normal CRP. RESULTS: In both gender, patients with elevated CRP had higher body mass index, waist circumference, fat mass, visceral fat, insulinemia, HbA1c, and lower muscle mass and insulin sensitivity. They had more atherogenic dyslipidemia, higher non-HDL-C and apolipoprotein B100, and more lipoprotein(a) (+59% in men and +38% in women). In both sexes, there was no difference between patients with normal or high CRP regarding overall macroangiopathy (42% vs. 45% [men]; 27% vs. 28% [women]), coronary and peripheral artery disease, or stroke. Only in men, microangiopathy was more prevalent when CRP was raised (61% vs 44%; p < 0.0001). CONCLUSIONS: This study shows major sex-related differences in microangiopathies in T2DM patients with high CRP levels. The latter are unrelated to prevalent CVD despite an unfavorable metabolic phenotype. By contrast, increased CRP may represent an extended biomarker of microvascular risk in men with T2DM.

Fibroblast growth factor 23 (FGF-23), a key hormone for the regulation of the phosphorus homeostasis, has also several direct effects on cardiac function. In heart failure (HF), the increase of FGF-23 participates to cardiac hypertrophy and remodeling. Measurement of the intact, biologically active hormone is now available. We determined intact FGF-23 in HF patients with reduced ejection fraction and assess its prognosis value for cardiovascular death over a long-term follow-up. We observed that intact FGF-23 is an independent predictor of cardiovascular death in HF patients and provides added value to the standard of care, natriuretic peptide, for risk estimation.

Cholesfytol, a lipid-lowering dietary supplement with antioxidant and anti-atherosclerotic properties, combines red yeast rice (RYR) and olive extract (5mg hydroxytyrosol equivalent) and represents an alternative for patients who do not wish or are unable to use chemical statins, including individuals with previous statin-associated muscle symptoms (SAMS). A 2-months observational non-randomized study was performed to evaluate the efficacy, tolerance and safety of Cholesfytol (1 tablet/day) in 642 hypercholesterolemic patients (mean age: 59 yrs; total cholesterol (TC) ≥200; LDL-C ≥140mg/dl). Patients were followed by 126 GPs, and included irrespective of SAMS history and/or diabetes. None of the patients were taking statins or other lipid-modifying therapy at inclusion. At baseline, 26% had fasting glucose >100 ≤125mg/dL, and 5% >125mg/dL; 32% (n=194) had a SAMS history; and 21% had atherogenic dyslipidemia (AD). In the entire cohort, pre-treatment TC; non-HDL-C; LDL-C; and TG were 259; 200; 168; 158mg/dL, respectively, and decreased significantly on treatment (-17.5% (TC) and -23.3% (LDL-C)). Fasting glucose and HbA decreased between visits. The reduction in lipids was greater in patients with higher values at baseline. For comparable pre-treatment values, patients with SAMS history had reductions in TC, LDL-C, non-HDL-C, and apoB slightly less than patients without myalgia. AD patients had greater on-treatment decrease in TG. Overall, 13 patients reported minor side-effects, and 4 patients reporting myalgia had antecedent SAMS. In conclusion, a substantial decrease in LDL-C was obtained with a combination of RYR and olive extract in high-risk hypercholesterolemic patients, without inducing new-onset SAMS.

BACKGROUND: Limited data are available regarding the prognostic value of right ventricular (RV) systolic dysfunction (RVSD) in patients with coronary artery disease. Our objective was to evaluate the effect of RVSD assessed by cardiac magnetic resonance on survival of patients with low left ventricular (LV) ejection fraction (EF) undergoing coronary bypass grafting (CABG). METHODS: We prospectively assessed overall and cardiovascular death of 107 consecutive patients (94 men; age, 66 ± 10 years) undergoing CABG who had a LVEF of 0.35 or less by cardiac magnetic resonance before CABG. RESULTS: Mean LVEF was 0.25 ± 0.07, and mean RVEF was 0.46 ± 0.16. RVSD, defined by RVEF of 0.35 or less, was present in 32 patients (30%). In-hospital mortality rate (n = 8) was significantly higher in patients with RVSD (18.7% vs 2.7%, p = 0.004). Over a median follow-up of 4.7 years, 44 patients died, 33 of a cardiovascular cause. The primary end point of cardiovascular death was reached by 15 of 32 patients with RVSD and 18 of 75 patients without RVSD (47% vs 24%, p = 0.019). Univariate survival analysis showed that age, New York Heart Association Functional Classification, diabetes, estimated glomerular filtration rate, LVEF, LV indexed end-diastolic volume, RVEF, RV indexed end-diastolic volume, RV systolic function, and The Society of Thoracic Surgeons risk score were independent predictors of the primary end point of cardiovascular death. By multivariable analysis, the Society of Thoracic Surgeons risk score (hazard ratio, 1.32; 95% confidence interval, 1.13 to 1.55; p = 0.001) and RVSD (hazard ratio, 2.14; 95% confidence interval, 1.06 to 4.31; p = 0.034) remained significant independent predictors of cardiovascular death. CONCLUSIONS: RVSD strongly and independently predicts cardiovascular death in patients with coronary artery disease and low EF undergoing CABG. Evaluation of RV function should thus be part of preoperative evaluation of such patients.

BACKGROUND: Type 2 diabetes (T2DM) is associated with obesity, insulin resistance and the metabolic syndrome (MetS). In non-diabetic populations, features of metabolic obesity (MO) are observed in a minority of normal-weight (NW) subjects. The cardiometabolic status of metabolically obese but normal-weight (MONW) individuals has not yet been phenotyped in T2DM. PATIENTS AND METHODS: Prevalence and features of MONW were analyzed in 1244 T2DM patients, in whom MONW was identified as a BMI <25.0 and a MetS score ≥3/5. Among NW (n=262; 21%), those without MetS (n=152; NW-MetS[-]) were compared to NW-MetS[+] (n=110; i.e. 42% of NW and 9% of all T2DM). RESULTS: There were no differences between groups in age; gender; diabetes duration; smoking; BP; and LDL-C. NW-MetS[+] had higher BMI; waist; fat mass; visceral fat; liver steatosis and HbA1c, and lower insulin sensitivity. Non-right-handedness was twice-higher (18%) in NW-MetS[-]. NW-MetS[+] had higher apoB100 and triglycerides, and lower HDL-C and LDL size. Macroangiopathy was present in 39% of NW-MetS[+] vs. 22% of NW-MetS[-], as coronary (23% vs. 14%) or peripheral artery disease (14% vs. 5%) and TIA/stroke (15% vs. 7%). Microangiopathy was present in 54% of NW-MetS[+] vs. 32% of NW-MetS[-], as retinopathy (25% vs. 13%); neuropathy (29% vs. 18%); and albuminuria (39% vs. 20%). CONCLUSIONS: MONW among T2DM represents a significant minority (about 1 in 10). Their cardiometabolic phenotype deserves attention due to multiple comorbidities, including a twice-higher prevalence of micro-/macrovascular damage in patients wrongly perceived at lower risk due to normal BMI. Unexpectedly, non-right-handedness was over-represented among metabolically healthy patients

Biomarkers offer new perspectives for a more personalized management of patients with heart failure (HF). Hyperparathyroidism is common in HF patients and parathyroid hormone (PTH) testing might provide added value for the prognostication of HF patients. Our objectives were therefore to determine the efficiency of multiple biomarker strategy based on PTH and natriuretic peptides measurement for the risk stratification of patients with HF. Circulating concentrations of bioactive PTH 1-84 and natriuretic peptides, B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP), were measured with automated immunoassays in 45 healthy individuals and 137 HF patients with reduced left ventricular ejection fraction. Circulating levels of PTH 1-84 and natriuretic peptides were significantly increased in HF patients in comparison to HF patients. Over a long-term follow-up, baseline PTH 1-84 levels were related to the risk of cardiovascular death. Furthermore, in multiple biomarker approach, PTH measurement was additive to BNP and NT-proBNP testing for the cardiovascular risk assessment of HF patients. In conclusion, the combination of PTH 1-84 and natriuretic peptides testing improves the prognostication of HF patients and might allowed more personalized approach for risk stratification and treatment selection in HF patients.

Background: Diabetes is a major cardiovascular risk factor. However, its influence on the rate of occurrence of cardiovascular (CV) events during a clinical trial that included a diabetes subgroup has not yet been quantified. Aims: To establish equations relating baseline diabetes prevalence and incident CV events, based on comparator arms data of major lipid-modifying trials. Methods: Meta-analysis of primary outcomes (PO) rates of key prospective trials, for which the baseline proportion of diabetics was reported, including studies having specifically reported CV outcomes within their diabetic subgroups. Results: 47 studies, representing 330,376 patients (among whom 124,115 diabetics), were analyzed as regards the relationship between CV outcomes rates (including CHD) and the number of diabetics enrolled. Altogether, a total of 18,445 and 16,156 events occurred in the comparator and treatment arms, respectively. There were significant linear relationships between diabetes prevalence and both PO and CHD rates (%/year): y = 0.0299*x + 3.12 [PO] (p = 0.0128); and y = 0.0531*x + 1.54 [CHD] (p = 0.0094), baseline diabetes predicting PO rates between 3.12 %/year (no diabetic included) and 6.11 %/year (all patients diabetic); and CHD rates between 1.54 %/year (no diabetic) and 6.85 %/year (all patients diabetic). The slopes of the equations did not differ according to whether they were derived from primary or secondary prevention trials. Conclusions: Absolute and relative CV risk associated with diabetes at inclusion can be readily predicted using linear equations relating diabetes prevalence to primary outcomes or CHD rates.

OBJECTIVES: The purpose of this study was to evaluate the impact of hypertrabeculation and left ventricular (LV) myocardial noncompaction phenotype by cardiac magnetic resonance (CMR) on outcomes of patients with nonischemic dilated cardiomyopathy (DCM). BACKGROUND: Myocardial trabeculations and noncompaction are increasingly observed in patients with DCM, but their prognostic impact remains unknown. METHODS: We prospectively evaluated outcomes of 162 consecutive patients (102 men; age 55 ± 15 years; ejection fraction [EF] 25 ± 8%) with DCM undergoing CMR. The amount of noncompaction was quantified as noncompacted/compacted (NC/C) length in the long-axis view and as the ratio of NC/C mass in the short-axis view and compared against 48 healthy control subjects (age 60 ± 10 years). RESULTS: Fifty-eight DCM patients (36%) had NC/C length ≥2.3, and 71 (44%) had NC/C mass greater than the 95% confidence interval (CI) of control subjects. NC/C length and NC/C mass did not correlate with any clinical, echocardiographic, or CMR parameters. Over a 3.4-year median follow-up, 29 patients experienced major adverse cardiovascular events (MACE) (12 cardiovascular deaths, 8 heart transplantations, 4 LV assist device implantations, and 5 resuscitated cardiac arrests or appropriate device shocks). Cox univariate analysis identified smoking, New York Heart Association functional class, blood pressure, LV and right ventricular end-diastolic and end-systolic volumes, LV EF, right ventricular EF, and late gadolinium enhancement as predictors of MACE. In multivariate analysis, only LV EF and late gadolinium enhancement were independent predictors of MACE-free survival (hazard ratio: 0.922, 95% CI: 0.878 to 0.967, p = 0.001 and HR: 1.096, 95% CI: 1.004 to 1.197, p = 0.04, respectively). Neither NC/C length nor NC/C mass had significant predictive value for MACE-free survival, either unadjusted or after adjustment for baseline variables. Also, there was no difference in cardioembolic event

Le diabète est un facteur de risque cardiovasculaire (CV) majeur; son influence sur le taux de survenue d’événements CV au cours d'un essai clinique qui inclut une sous-cohorte de diabétiques n'a pas encore fait l'objet d'une évaluation quantifiée. Ce travail a déterminé dans quelle mesure un diabète à l'inclusion, à titre individuel ou à un niveau de sous-groupe de patients, augmente le risque résiduel CV au cours d'un essai clinique randomisé. Cette méta-analyse a repris les critères principaux d’essais prospectifs- clés, pour lesquels la proportion de diabétiques à l’inclusion était connue, y compris les études ayant spécifiquement rapporté des résultats pour leurs sous-groupes de diabétiques. L’analyse a permis de quantifier formellement la relation linéaire entre la prévalence du diabète et les taux de maladies CV. La composante de risque CV absolu et relatif résiduel associé à la présence à l’inclusion de diabétiques peut ainsi être facilement prédite à partir d’équations linéa, [Treatment of dyslipidemia and cardiovascular risk in diabetes: a meta-analysis of 198.930 patients included in 57 randomized studies] Diabetes is a major cardiovascular (CV) risk factor; its influence on the rate of occurrence of CV events during a clinical trial that includes a sub-cohort of diabetics has not been quantified. This work determined the extent to which diabetes at baseline, individually or at a sub-group level, increases residual CV risk during a randomized clinical trial. This meta-analysis reviewed landmark prospective lipid-lowering trials for which the proportions of diabetes at baseline were known, including studies having specifically reported results for their diabetic subgroups. The analysis allowed to formally quantify the linear relationship between the prevalence of diabetes at baseline and primary CV outcomes rates. The absolute residual CVD risk component associated with the presence of diabetes at inclusion can be easily predicted from these linear equations relating the prevalence of diabetes to various CV outcomes.

Objectives: Vitamin D deficiency and hyperparathyroidism are common in patients with heart failure (HF). There is a growing body of evidence supporting the role of vitamin D and parathyroid hormone (PTH) in cardiac remodeling and worsening of HF. Lack of reliable automated testing of 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active metabolite of vitamin D, has limited its contribution to the prognostic assessment of HF. Here, the association of 1,25(OH)2D and PTH(1–84) levels was evaluated for prediction of cardiovascular death in chronic HF patients. Methods: We conducted a single center prospective cohort including 170 chronic HF patients (females n = 36; males n = 134; NYHA II-IV; mean age: 67 years; etiology: ischemic n = 119, dilated cardiomyopathy n = 51; mean LVEF: 23%). The primary outcome was cardiovascular death. Results: Serum levels of 1,25(OH)2D decreased markedly with increased HF severity. Medians were 33.3 pg/mL for NYHA-II patients, 23.4 pg/mL for NYHA-III, and 14.0 pg/mL for NYHA-IV patients (p<0.001). Most patients had levels of 25(OH)D below 30ng/mL, and stratification by NYHA functional class did not show significant differences (p = 0.249). The 1,25(OH)2D to PTH(1–84) ratio and the (1,25(OH)2D)2 to PTH(1–84) ratio were found to be the most significantly related to HF severity. After a median follow-up of 4.1 years, 106 out of 170 patients reached the primary endpoint. Cox proportional hazard modeling revealed 1,25(OH)2D and the 1,25(OH)2D to PTH(1–84) ratios to be strongly predictive of outcomes. Conclusions: 1,25(OH)2D and its ratios to PTH(1–84) strongly and independently predict cardiovascular mortality in chronic HF.