Cystatin C, NT-proBNP, and inflammatory markers in acute heart failure: insights into the cardiorenal syndrome.

BACKGROUND: Inflammation is thought to be a mediator in the pathophysiology of the cardiorenal syndrome. We evaluated the interactions between kidney function, cardiac stress, and various inflammatory cytokines in patients with acute heart failure (AHF). The effect on 1-year mortality was also assessed. METHODS AND RESULTS: Plasma levels of cystatin C, NT-proBNP, and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-α [TNF-α], IL-10) were measured in consecutive patients (n = 465) hospitalized for AHF. After adjustment for demographic characteristics and comorbidities, TNF-α had the strongest relation with renal function (ß = 0.39, P < 0.0001). Elevated TNF-α levels were seen in patients with high cystatin C, irrespective of NT-proBNP. Levels of IL-6 (ß = 0.26, P < 0.0001) and IL-10 (ß = 0.15, P < 0.01), but not TNF-α, were associated with NT-proBNP. Moreover, the most elevated levels of IL-6 were seen in patients with combined high NT-proBNP and high cystatin C. Cox regression analysis found IL-6 above median to be independently predictive of mortality (hazard ratio 1.9; 95% CI 1.2-2.9, P = 0.003). TNF-α was not significantly associated with prognosis in the overall population after adjustment for multiple covariates, but improved risk stratification in the subgroup with low cystatin C and NT-proBNP. CONCLUSION: Levels of TNF-α in AHF are related to kidney function, but not to NT-proBNP. IL-6 seems to be more associated with cardiac stress. Patients with severe dual organ dysfunction have the highest levels of IL-6 and TNF-α. Different relations of inflammatory cytokines to renal function and cardiac stress need to be considered when evaluating heart--kidney interactions.

Insertion-deletion polymorphism in the gene for angiotensin-converting enzyme is associated with obstetric cholestasis but not with preeclampsia.

OBJECTIVE: Our purpose was to investigate the contribution of angiotensin-converting enzyme insertion-deletion polymorphism in the development of obstetric complications. STUDY DESIGN: In a retrospective case-control study, angiotensin-converting enzyme insertion-deletion polymorphism was investigated in a control group of healthy women (n = 115) and in a group of women diagnosed with preeclampsia (n = 133) and obstetric cholestasis (n = 57). Polymerase chain reaction detection of insertion-deletion polymorphism was used to determine the presence of the two angiotensin-converting enzyme alleles in the groups; the frequencies in the general population in our area are presented for comparison. RESULTS: The frequency of the D allele was 43.9% among women with obstetric cholestasis and 27% among healthy fertile women, which is close to the rate in the general population in our area (28%). The odds ratio for obstetric cholestasis associated with the DD genotype was 2.12 (95% CI, 1.08-4.12) compared with the pooled II and ID genotypes (P = .03). Neither the ID genotype distributions nor the allele frequencies differed significantly between preeclamptic and normotensive pregnancies (P = .36). CONCLUSION: The present data indicate that the DD genotype is a genetic marker associated with an elevated risk of obstetric cholestasis, but this polymorphism of the angiotensin-converting enzyme gene is unlikely to play any significant role in preeclampsia.