Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure

OBJECTIVES: The study evaluated the transcardiac extraction or spillover of aldosterone (ALDO) in normal subjects and in patients with congestive heart failure (CHF). BACKGROUND: Aldosterone promotes collagen synthesis and structural remodeling of target organs such as the heart. Spironolactone, an ALDO receptor antagonist, has recently been reported to reduce the mortality of patients with CHF; however, the effects of spironolactone on the transcardiac gradient of ALDO have not been clarified. METHODS: We measured plasma ALDO in the aortic root (AO) and coronary sinus (CS) in normal subjects and 113 consecutive CHF patients and also measured plasma procollagen type III aminoterminal peptide (PIIINP) in CS, a biochemical marker of myocardial fibrosis. RESULTS: Plasma ALDO was significantly lower in the CS than in the AO in normal subjects (n = 15; 61.2 +/- 9.3 vs. 83.1 +/- 11.8 pg/ml, p < 0.0001). In 96 CHF patients who did not receive spironolactone, plasma ALDO was significantly lower in the CS than in the AO (59.3 +/- 3.9 vs. 73.8 +/- 4.9 pg/ml, p < 0.0001). In contrast to the difference in these 96 patients, there was no significant difference in ALDO between the AO and CS in 17 patients who received spironolactone (127.4 +/- 20 vs. 124.0 +/- 19 pg/ml, p = 0.50). Stepwise multivariate analyses showed that spironolactone therapy had an independent and significant negative relationship with the transcardiac gradient of plasma ALDO in patients with CHF. In addition, significant positive correlations were seen between the transcardiac gradient of plasma ALDO and PIIINP (r = 0.565, p < 0.0001) and the left ventricular end-diastolic volume index (r = 0.484, p < 0.0001). CONCLUSIONS: These results indicate that plasma ALDO is extracted through the heart in normal subjects and in CHF patients who do not receive spironolactone and that spironolactone inhibits the transcardiac extraction of ALDO in CHF patients, suggesting that spironolactone blocks the effects of ALDO on the failing heart in patients with CHF.     

The relationship between pulse wave velocity and indexes of collagen synthesis in hypertensive patients, according to the level of systolic blood pressure

Vascular stiffening, a process responsible for the development of isolated systolic hypertension, depends on dysregulation of collagen-elastine production and arrangement, yet it is not known whether the effect is uniform throughout wide blood pressure (BP) range. To check whether arterial stiffness is similarly related to increased fibrotic remodelling, in patients with systolic blood pressure (SBP) above and below 160 mmHg. Consecutive peri- and postmenopausal female outpatients treated for hypertension and free from other disorders interfering with fibrotic processes, had their BP, pulse wave velocity (PWV), and collagen (N-terminal procollagen type III propeptide (PIIINP); C-terminal procollagen type I propeptide-(PICP)) measured. The average age of 100 women was 71.8+/-10.5 years, BP was 145/83+/-25/15 mmHg, pulse pressure 63+/-17 mmHg, and mean blood pressure (MBP) 104+/-17 mmHg. PWV was 12.9+/-3.6 m/s and was significantly higher among 30 patients with SBP of > or =160 mmHg. PIIINP averaged 4.6+/-1.6 ng/ml and PICP 142.2+/-47.0 ng/ml. In the low SBP (<160 mmHg) group there was no relationship between PWV and collagen concentrations. However, in the > or =160 mmHg group there was significant correlation between PWV and PIIINP concentration. The relationship held significant after adjustment for age, and BP components. Our result can help explaining the results of recent intervention trials where older patients tended to benefit more from potentially antifibrotic drugs (ACE-I), whereas those with compliant arteries tend to benefit from diuretics.     

急性心肌梗死后螺内酯干预对左室重构的影响

目的　探讨急性心肌梗死(AMI)患者应用螺内酯干预对于左室重构(LVRM)的影响。方法　4家医院共入选AMI患者88例,采用多中心、随机、对照的方法,对46例AMI患者在常规治疗的基础上加用螺内酯40mg/d(螺内酯组),对照组(n=42)常规治疗。在6个月干预期内检测两组血清Ⅲ型前胶原氨基端肽(PⅢNP)、脑钠肽(BNP)及超声心动图,以评价左室纤维化、左室功能和左室容积。结果　88例中,急性前壁心肌梗死患者43例,螺内酯组23例、对照组20例;急性下壁心肌梗死患者45例,螺内酯组23例、对照组22例。急性前壁心肌梗死组在治疗3、6个月时螺内酯组与对照组相比,血清PⅢNP和BNP明显降低[PⅢNP分别为( 260 .2±59. 9 )ng/L比( 328 .0±70 .3 )ng/L, P=0 .001, ( 197 .1±46 .3 )ng/L比( 266. 7±52 .4 )ng/L, P<0. 001 ,BNP分别为( 347 .4±84 .0)ng/L比(430 .1±62 .9)ng/L, P<0 .001, (243 .7±79. 7)ng/L比(334. 6±62. 8)ng/L, P<0. 001]。治疗6个月时螺内酯组较对照组左室舒张末期内径、左室收缩末期内径明显降低[分别为(51. 0±5 .5)mm比(55. 6±4 .5)mm, P=0 .005, (35 .7±4 .6)mm比(39 .1±5 .6)mm, P=0 .046]。急性下壁心肌梗死组在治疗6个月时螺内酯组与对照组相比血清PⅢNP、BNP水平无统计学意义,(P>0 05),并且左     

急性心肌梗死患者血B-型尿钠肽水平的变化特点

目的观察急性心肌梗死(AMI)后血B-型尿钠肽(BNP)水平升高的特点,探讨AMI后BNP水平升高的意义。方法连续入选住院AMI患者230例及正常对照111例进行BNP测定。按照首次或再发AMI后ST段抬高型或非ST段抬高型AMI(STEMI或NSTEMI)、不同部位AMI、不同冠状动脉病变、不同梗死相关血管(IRA)、IRA不同TIMI血流和是否急诊经皮冠状动脉介入治疗(PCI)进行分组,采用Student-t检验和ANOVA分析对比各组间BNP水平和心功能相关指标的差异。结果AMI后2~7天,患者BNP水平显著升高(P<0.01),平均为(553.7±735.1)ng/L,是对照组的21倍;与首次AMI组对比,再发组左室射血分数(LVEF)显著降低(P<0.01),左室舒张末径(LVEDd)、BNP水平和LnBNP均显著升高(P均<0.01);与无显著狭窄病变AMI患者对比,单支、三支血管狭窄组的BNP水平显著为高(P均<0.05);IRA的TIMI血流0~1、2级组BNP水平均显著高于TIMI血流3级组(P均<0.01);与未急诊PCI组对比,急诊PCI组血肌酸激酶同工酶(CK-MB)、肌钙蛋白T(TnT)虽显著升高(P<0.05~0.01),然BNP水平显著降低(P<0.05)。结论AMI后,血BNP水平显著升高。以再发AMI、未行急诊PCI治疗和IRA血流TIMI0~2级者更高。急诊PCI可出现心肌酶升高,而BNP降低的矛盾现象。     

GDF-15与心肌梗死后心室重塑指标的相关性分析

目的：探讨心肌梗死后心力衰竭患者血清生长分化因子-15（GDF-15）水平的变化,及与心功能和心肌纤维化指标的相关性。方法：人选急性心肌梗死后心力衰竭患者100例为心衰组,健康体检者50例为健康对照组。检测并分析两组患者GDF-15水平的变化,及其与心功能[左心室收缩期内径（LVESd）、舒张末期内径（LVEDd）、左室射血分数（LVEF）]和心肌纤维化相关指标[脑钠肽（BNP）、血清转化生长因子（TGFp、I型前胶原氨基端肽（PINP）和Ⅲ型前胶原氨基端肽（PIIINP）]的相关性。结果：与健康对照组相比,心衰组血清GDF-15[（623．56±70．21）ng／L比（2003．53±163．2）ng／L]、TGFβ[（21．5±6．80）ng／ml比（58．93±12．81）ng／ml]、PINP[（150．58±32．57）ng／ml比（233．15±26．94）ng／ml]和PIIINP[（17．56±8．72）ng／ml比（48．64±9．28）ng／ml]明显升高（P〈0．05~〈0．01）。随着心功能分级的增加（Ⅱ-Ⅳ）,GDF-15的水平明显升高[（1521．32±98．23）ng／L比（2311．92±108．52）ng／L比（3023．54±129．36）ng／L,P均〈O．01]。Pearson相关分析结果显示,心肌梗死后心力衰竭患者血清GDF-15水平与LVEF呈负相关（r=-0．574,P〈O．05）,与LVESd和LVEDd呈正相关（r=0．688,0．752,P均〈0．05）;GDF-15水平与血浆BNP,血清PINP、PIIINP和TGFβ水平呈正相关（r=0．568～0．82,P均〈0．05）。结论：生长分化因子-15参与心肌梗死后心力衰竭患者的心室重塑。     

Evaluation of cardiac structure by echoreflectivity analysis in acromegaly: effects of treatment

OBJECTIVES: Cardiac echoreflectivity is a noninvasive tool for evaluating cardiac fibrosis. The present paper aimed to study the modifications of cardiac echoreflectivity in a group of acromegalic patients before and after therapy, and to assess possible correlations with serum levels of procollagen III (PIIINP), a peripheral index of collagen synthesis. DESIGN AND METHODS: Cardiac echoreflectivity (as assessed by analyzing 2-D echocardiograms digitized off-line onto a personal computer) and PIIINP levels were evaluated in 16 acromegalic patients of new diagnosis not affected by arterial hypertension (10 males, six females, age+/-s.d.: 38+/-10 years), and in a group of 16 sex- and age-matched healthy subjects. All the patients were re-evaluated after surgical and/or medical therapy for acromegaly. The echo patterns were analyzed by software that supplies the derived collagen volume fraction (dCVF), an index of fibrosis. RESULTS: At baseline, acromegalic patients showed significantly higher dCVF values and PIIINP levels than healthy controls (3.1+/-0.5% vs 1.6+/-0.3%, P<0.01 and 8.7+/-2.2 vs 3.1+/-1.1 ng/ml, P<0.05, respectively, by unpaired Student's t-test). After therapy, dCVF and PIIINP levels normalized in the six controlled patients (that is, GH of <2.5 microg/l and IGF-I within normal range) (dCVF from 2.8+/-0.4% to 1.4+/-0.2%, P<0.001; PIIINP from 8+/-2.7 to 3.3+/-1.9 ng/ml, P<0.05), while no significant changes were found in noncontrolled patients (dCVF from 3.3+/-0.6% to 2.9+/-1.2% and PIIINP from 9.1+/-1.9 to 7.9+/-3.5 ng/ml, P=NS). A positive correlation between dCVF and PIIINP (r=0.75, P<0.001) and between IGF-I and both dCVF and PIIINP (r=0.65 and 0.61 respectively, P<0.05) was found in acromegalic patients. CONCLUSIONS: Cardiac echoreflectivity, which may be a reflection of heart collagen content, is increased in patients with active acromegaly and correlates with PIIINP concentrations. After cure or adequate control of the disease, both parameters revert to normal. Echoreflectivity analysis could be a useful adjuvant parameter in the assessment of the activity of acromegalic disease.     

Effects of 12 months rec-GH therapy on bone and collagen turnover and bone mineral density in GH deficient children with thalassaemia major

Children suffering from thalassaemia major are reported to have growth delay and bone alterations even when well transfused and chelated. In the present study we evaluated bone and collagen turnover (bone Gla-protein, BGP; carboxyterminal telopeptide of type I collagen, ICTP; aminoterminal propeptide of type III procollagen, PIIINP, respectively) and bone mineral density (BMD) in 5 pre-pubertal GH deficient thalassaemic children before and during rec-GH treatment (0.6 IU/kg/week). Data were compared with those recorded in an age- and sex-matched control group. Before treatment, serum BGP and ICTP levels were significantly lower (p<0.0001) in children with thalassaemia (9.3+/-0.7 ng/ml and 5.3+/-0.5 ng/ml, respectively) than in healthy controls (18.9+/-0.9 ng/ml and 14.4+/-0.6 ng/ml, respectively), while serum PIIINP levels did not significantly differ in the two groups (6.7+/-0.7 ng/ml vs 6.7+/-0.7 ng/ml). Mean lumbar BMD values of patients (0.62+/-0.05 g/cm2) were significantly lower (p<0.05) than those recorded in healthy controls (0.78+/-0.01 g/cm2), while femoral BMD values were similar in the two groups (patients: 0.70+/-0.08 g/cm2 vs controls: 0.74+/-0.01 g/cm2). One-year GH therapy significantly increased height velocity (from 2.3+/-0.2 cm/year to 6.1+/-0.4 cm/yr, p<0.0001) and IGF-I levels (from 61.6+/-15.4 to 342+/-38.5 ng/ml, p<0.005). Serum BGP (basal: 9.3+/-0.7 ng/ml, 6th month: 10.8+/-0.6 ng/ml, 12th month: 14.9+/-1.4 ng/ml), ICTP (basal: 5.3+/-0.5 ng/ml, 6th month: 7.9+/-0.8 ng/ml, 12th month: 10.9+/-1.7 ng/ml) and PIIINP levels (basal: 6.7+/-0.7 ng/ml, 6th month: 9.9+/-1.0 ng/ml, 12th month: 9.6+/-1.4 ng/ml) significantly increased (p<0.05), while no significant effects were observed on lumbar and femoral BMD values. Although the GH-induced stimulation of bone turnover markedly increased BGP (+60%) and ICTP (+105%) levels, one-year GH therapy was not sufficient to completely normalize these parameters, which remained significantly lower than in healthy controls. In conclusion, our study shows that pre-pubertal GH deficient children with thalassaemia major have reduced bone turnover (both bone formation and resorption) and lumbar BMD values, thus indicating that bone metabolism should be monitored and improved even in well-transfused patients. One-year GH treatment is able to increase, but not normalize, bone turnover, this effect being insufficient to improve BMD values. More prolonged periods of GH therapy are probably requested to positively affect both bone turnover and BMD values in GH deficient thalassaemic patients, as occurs in children and adults with GH deficiency.     

Elite volunteer athletes of different sport disciplines may have elevated baseline GH levels divorced from unaltered levels of both IGF-I and GH-dependent bone and collagen markers: a study on-the-field

Seventy-seven Italian eliteathletes(42 M, 35 F, mean age +/- SE: 24.4-0.7 yr, age range: 17-47 yr) of different sport disciplines (sprinters, triathletes, middle-distance runners, road-walkers, cyclists, rowing athletes, skiers, roller hockey players, swimmers) were sampled on-the-field (before a training session) for the determination of basal GH, IGF-I, C-terminal cross-linked telopeptide of type I collagen (ICTP) and amino-terminal propeptide of type III procollagen (PIIINP) levels, two GH-dependent peripheral markers of bone and collagen turnover, respectively. Basal GH concentrations were significantly higher (p<0.001) in female (5.8 +/- 1.0 ng/ml) vs male athletes (1.8 +/- 0.5 ng/ml), with a large spread of values in either gender. Mean GH levels of athletes were significantly higher than those recorded in age-matched sedentary controls (females: 2.5 +/- 0.5 ng/ml, p<0.001; males: 0.5 +/- 0.2 ng/ml, p<0.05). Among female athletes, 7/35 had basal GH values higher than the upper limit of control values (>9.5 ng/ml), while among males 7/42 had values higher than the upper limit of male sedentary controls (>3.6 ng/ml). No significant differences in basal GH concentrations were found between females taking oral contraceptives (OC) and those who did not receive this treatment (5.0 +/- 2.1 vs 6.0 +/- 1.2 ng/ml). IGF-I levels (236.4 +/- 7.8 ng/ml) were in the normal range for age in all athletes (except for 1 athlete with slightly increased levels), no significant correlation being found between GH and IGF-I levels (R2=0.0393). Mean ICTP (4.6 +/- 0.2 ng/ml) and PIIINP (4.4-0.1 ng/ml) concentrations of elite athletes were not significantly different from those recorded in age and matched healthy sedentary subjects; 4 athletes showed increased PIIINP levels and 2 had increased ICTP levels. ICTP and PIIINP levels were positively correlated with chronological age (p<0.001), a positive correlation being also found between the two markers (p<0.001). On the contrary, no significant correlation was found between basal GH/IGF-I levels and ICTP/PIIINP levels. In conclusion, the present study demonstrates that: 1) elite athletes (particularly females), which have frequently increased basal GH on-the-field, have actually normal IGF-I levels; 2) ICTP and PIIINP levels of athletes are similar to those recorded in healthy sedentary, being significantly higher in younger subjects of both groups; 3) the presence of increased basal GH levels, being associated with normal IGF-I, ICTP and PIIINP levels, is probably the result of a transient GH peak in this study group. Further additional studies are requested to verify the possible use of these peripheral GH-dependent markers for detecting exogenous chronic administration of recombinant GH in athletes.     

The dissociation of renin and aldosterone during critical illness

A syndrome of elevated PRA accompanied by inappropriately low plasma aldosterone (ALDO) levels has been identified in some critically ill patients. To determine whether this phenomenon is due to a disturbance in factors that stimulate ALDO, we measured PRA, angiotensin II (AII), potassium (K+), and ACTH levels in 83 patients admitted to an intensive care unit. In 59 patients, PRA was greater than 2.0 ng/ml X h. Of these, 24 had an ALDO to PRA ratio (ALDO/PRA) below 2 (group I), and 35 had an ALDO/PRA ratio of 2 or more (group II). An ALDO/PRA ratio below 2 was deemed inappropriately low. Despite markedly elevated PRA [34 +/- 12 (+/- SE) ng/ml X h], the group I patients had inappropriately low ALDO levels (19 +/- 5 ng/dL). Patients in group II had significantly higher ALDO levels (48 +/- 6 ng/dL) despite lower PRA (9 +/- 1 ng/ml X h). AII levels were appropriately elevated in group I (39 +/- 26 pg/mL) and significantly greater (P less than 0.5) than those in group II. PRA correlated well with AII in both groups. There were no differences in plasma ACTH or K+ in these 2 groups, and plasma cortisol levels were similarly elevated in both groups of patients. Of 66 consecutively studied patients, 14 (21%) had inappropriate ALDO (group I). Mortality was significantly greater in group I (75%) than in group II (46%; P less than 0.001). In summary, a significant subset (21%) of seriously ill patients have inappropriately low ALDO levels despite elevated PRA. This dissociation is not due to an impairment of AII production or changes in plasma ACTH or K+. This phenomenon is associated with a higher mortality during critical illness. In light of evidence of decreased adrenal androgen secretion during severe illness, this dissociation of renin and aldosterone may represent an additional adrenal adaptation designed to promote cortisol production in critically ill patients.     

Different effects of thyroid disease on serum levels of procollagen III N-peptide and hyaluronic acid

Serum levels of procollagen III N-peptide (PIIINP) and hyaluronic acid (HA) reflect secretion of procollagen III and HA from fibroblasts, a cell type sensitive to thyroid hormones. Serum PIIINP and HA concentrations were measured in different thyroid function states, the former by two different assays, one detecting intact and aggregated PIIINP (PIIINP assay) and another detecting low mol wt degradation products of PIIINP as well (Fab-PIIINP assay). Two thirds of 28 hyperthyroid patients had elevated serum PIIINP values (mean, 192% in the PIIINP assay and 243% in the Fab-PIIINP assay) compared to age- and sex-matched controls (P less than 0.001). Normalization was seen after medical treatment (n = 16). In contrast, serum HA levels increased from 49 +/- 30 to 68 +/- 37 ng/mL (P less than 0.01) when a euthyroid state was achieved. Hypothyroid patients (n = 23) had increased serum HA levels (mean, 162%; P less than 0.05), which normalized after L-T4 treatment (71 +/- 50 before and 41 +/- 20 ng/mL after treatment (n = 16; P less than 0.02). L-T4 treatment also increased serum PIIINP levels significantly. Subjects with familial dysalbuminemic hyperthyroxinemia (n = 8), representing a situation with elevated circulating levels of T4 due to enhanced protein binding, and patients with nontoxic goiter with serum TSH levels ranging from 3.6-0.05 mU/L had normal serum levels of PIIINP and HA. Our data suggest that the secretion of procollagen III and that of HA from fibroblasts are influenced differently by thyroid hormones, since the secretion of procollagen III seems enhanced by thyroid hormones, whereas the secretion of HA seems reduced. Neither euthyroidism with enhanced serum T4 levels (familial dysalbuminemic hyperthyroxinemia) nor euthyroidism with reduced serum TSH levels (nontoxic goiter) seems associated with alterations at the connective tissue level.     

Utility of metabolic exercise testing in distinguishing hypertrophic cardiomyopathy from physiologic left ventricular hypertrophy in athletes

OBJECTIVES: This study evaluated the role of metabolic (cardiopulmonary gas exchange) exercise testing in differentiating physiologic LVH in athletes from HCM. BACKGROUND: Regular intensive training may cause mild increases in left ventricular wall thickness (LVWT). Although the degree of left ventricular hypertrophy (LVH) is typically less than that seen in hypertrophic cardiomyopathy (HCM), genetic studies have shown that a substantial minority of patients with HCM have an LVWT in the same range. The differentiation of physiologic and pathologic LVH in this "gray zone" can be problematic using echocardiography and electrocardiography alone. METHODS: Eight athletic men with genetically proven HCM and mild LVH (13.9 +/- 1.1 mm) and eight elite male athletes matched for age, size and LVWT (13.4 +/- 0.9 mm) underwent symptom limited metabolic exercise stress testing. Peak oxygen consumption (pVO2), anaerobic threshold, oxygen pulse and respiratory exchange ratios were measured in both groups and compared with those observed in 12 elite and 12 recreational age- and size-matched athletes without LVH. RESULTS: Elite athletes with LVH had significantly greater pVO2 (66.2 +/- 4.1 ml/kg/min vs. 34.3 +/- 4.1 ml/kg/min; p < 0.0001), anaerobic threshold (61.6 +/- 1.8% of the predicted maximum VO2 vs. 41.4 +/- 4.9% of the predicted maximum VO2; p < 0.001) and oxygen pulse (27.1 +/- 3.2 ml/beat vs. 14.3 +/- 1.8 ml/beat; p < 0.0001) than individuals with HCM. A pVO2 >50 ml/kg/min or >20% above the predicted maximum VO2 differentiated athlete's heart from HCM. CONCLUSIONS: Metabolic exercise testing facilitates the differentiation between physiologic LVH and HCM in individuals in the "gray zone."     

Long-term monitoring of rec-GH treatment by serial determination of serum aminoterminal propeptide of type III procollagen in children and adults with GH deficiency

Serum aminoterminal propeptide of type III procollagen (PIIINP) levels, a reliable marker of collagen formation, were evaluated in children (C=7) and adults with childhood-onset (CO=10) and acquired (A=18) GH deficiency (GHD) before, during and after withdrawal of rec-GH therapy (C=0.6 IU/kg/week, CO=0.5 IU/kg/week, A=0.25 IU/kg/week). The duration of treatment was 12 months for C and A and 6 months for CO; investigations were carried out before and at 3, 6, 9 and 12 months (for C and A) and at 3 and 6 months (for CO) of GH treatment and 6 months after the withdrawal of therapy (for A and CO). Data obtained from patients were compared with those recorded in two age- and sex-matched control groups. Before treatment, serum PIIINP levels were significantly lower (p<0.001) in C with GHD (mean+/-SE: 2.9+/-0.4 ng/ml) than in controls (6.1+/-0.4 ng/ml), while no significant differences were recorded between adults with CO/A-GHD (3.7+/-0.5 ng/ml and 3.4+/-0.2 ng/ml) and controls (3.2+/-0.2 ng/ml). GH treatment caused a significant increase (p<0.0001) of PIIINP levels both in C (3rd month: 4.4+/-0.2 ng/ml, 6th month: 5.1+/-0.4 ng/ml, 12th month: 5.1+/-0.5 ng/ml), CO-GHD (3rd month: 12.7+/-1.2 ng/ml; 6th month: 10.2+/-0.6 ng/ml) and A-GHD (3rd month: 10.0+/-1.0 ng/ml; 6th month: 8.4+/-0.6 ng/ml; 12th month: 7.0+/-0.7 ng/ml), the increase being dose-dependent (more marked and sustained in adults with CO-GHD). The maximal stimulation of collagen synthesis occurred after 3 months of GH treatment in adults with GHD, while a more gradual and less relevant increase was observed in C with GHD. Six months after the withdrawal of GH therapy, serum PIIINP levels of adults with CO-GHD (3.6+/-0.3 ng/ml) were similar to those recorded before treatment, while in adults with A-GHD serum PIIINP levels (2.6+/-0.2 ng/ml) were significantly lower (p<0.01) than in basal condition. In conclusion, our study shows that: a) GHD is associated with a reduction of soft tissue formation in children, while it seems to exert no relevant effects in adults with GHD; b) GH therapy causes a rapid stimulation of collagen turnover, which shows a different pattern in children and adults; c) the GH-induced stimulation of collagen synthesis is rapidly removed after the withdrawal of GH treatment. For these reasons, the determination of peripheral markers of GH effects appears useful for the monitoring of GH therapy and can contribute to assess the "tailored" substitutive dose for the individual patient.     

B型尿钠肽水平对急性心肌梗死患者心源性死亡的预测价值

目的 探讨急性心肌梗死（AMI）患者血B型尿钠肽（BNP）水平预测死亡的价值。方法对264例AMI患者随访（14．7±5．3）个月,随访率为87．1％。检测肌酸激酶同工酶（CK—MB）、肌钙蛋白（TnT）、左室舒张末径、左室射血分数和BNP,并绘制受试者工作特性曲线（ROC）对比评价BNP等指标对AMI后心源性死亡的预测价值。结果ROC曲线显示仅BNP能预测心源性死亡。据ROC曲线定864ng／L为最佳分界值时,预测AMI后1、6个月和1年时心源性死亡的敏感性、特异性、准确度、阳性和阴性预测值分别为76．2％-92．9％、84．3％-85．6％、82．2％-86．1％、21．3％-36．2％和97．3％-98．9％。多元回归分析显示BNP是预测AMI后近、远期心源性死亡的独立危险因素（P〈0．01）。BNP≤864ng／L组1年无心源性死亡生存率显著高于BNP〉864ng／L组（97．3％比72．3％,P〈0．001）,死亡者中位生存时间在前者亦显著长于后者（16．0比10．7个月,P〈0．01）,且与急诊PCI和ST段抬高与否无关。结论 与传统指标相比BNP水平能预测AMI患者心源性死亡,且预测作用最佳。     

Left ventricular hypertrophy and geometry in untreated essential hypertension is associated with blood levels of aldosterone and procollagen type III amino-terminal peptide.

BACKGROUND: The present study examined the role of aldosterone in left ventricular hypertrophy (LVH) and geometry in patients with untreated essential hypertension (EHT), and investigated the contribution of myocardial fibrosis to the process of LVH. METHODS AND RESULTS: The relationship of the plasma aldosterone concentration (PAC) to LVH and left ventricular (LV) geometry was investigated in 57 consecutive patients with untreated EHT. PAC correlated with both LV mass index (LVMI: r=0.46, p=0.0004) and relative wall thickness (RWT: r=0.33, p=0.013). In patients with LVH (LVMI > or =125 g/m(2)), the serum concentration of procollagen type III amino-terminal peptide (PIIINP), a marker of myocardial fibrosis, correlated with RWT (r=0.46, p=0.029). These patients were divided into 2 groups: concentric hypertrophy (CH) with RWT > or =0.44, and eccentric hypertrophy (EH) with RWT <0.44. The serum PIIINP concentration was significantly higher in the CH group than in the EH group (0.52+/-0.02 ng/ml vs 0.44+/-0.03 ng/ml, respectively; p<0.05). CONCLUSIONS: Aldosterone may be involved in LVH and LV geometry, particularly in the development of CH. Myocardial fibrosis seems more strongly involved in the hypertrophic geometry of CH than with EH.     

Serum carboxy terminal propeptide of type I procollagen to amino terminal propeptide of type III procollagen ratio is a better indicator than each single propeptide and 7S domain type IV collagen for progressive fibrogenesis in chronic viral liver diseases

Twenty chronic viral hepatitis patients, mainly with hepatitis B related with progression to liver cirrhosis were included for an assay of serum collagen markers: PICP (carboxy terminal propeptide of type I procollagen), PIIINP (amino terminal propeptide of type III procollagen), and 7S-IV (7S-domain type IV collagen). PICP is increased in 20% of chronic hepatitis patients with a mean of 190.3 ng/ml, which is not different from that of the follow-up concentration in liver cirrhosis, where 35% of cases were abnormal with a mean of 220.5 ng/ml. The serum level and percent of abnormality of PIIICP in chronic hepatitis and in liver cirrhosis are 23.5 ng/ml vs 14.8 ng/ml and 90% vs 100%, respectively (P>0.05). PICP/PIIINP is significantly higher during liver cirrhosis (15.11 vs 10.08,P<0.05). PICP during chronic hepatitis is not related to serum biochemical changes, while PICP during liver cirrhosis and PIIINP are correlated with hepatic enzymes. 7S-IV in chronic hepatitis and in liver cirrhosis is 14.0 ng/ml vs 10.9 ng/ml, respectively; both were positively correlated with hepatic enzymes. These results suggest that PICP/PIIINP is a better indicator of hepatic fibrogenesis than either PICP or PIIINP alone in viral hepatitis. A ratio of more than 12 is suggestive of liver cirrhosis.     

慢性心力衰竭患者血浆BNP、IL-27水平及其临床意义

目的探讨血浆脑钠肽(BNP)、白介素-27(IL-27)的水平变化在慢性心力衰竭(chronic heart failure,CHF)发生发展中的临床意义。方法选取50例CHF患者作为观察组,50例健康人作对照组。采用酶联免疫吸附法检测血浆中BNP、IL-27水平变化,观察不同程度CHF患者左心室射血分数(LVEF)与血浆BNP、IL-27的关系。结果观察组血浆BNP的表达水平[(512.42±324.43)pg/ml]明显高于对照组[(30.50±20.30)pg/ml](P0.05),血浆IL-27表达水平[(0.58±0.21)pg/ml]低于对照组[(0.89±0.43)pg/ml],且BNP与IL-27的表达水平呈负相关(r=-0.54,P0.05)。血浆BNP水平从心功能Ⅱ级[(756.45±184.82)pg/ml]、心功能Ⅲ级[(1090.78±220.32)pg/ml]、心功能Ⅳ级[(2130.26±265.89)pg/ml]依次上升,差异有统计学意义(P0.05);IL-27表达水平从心功能Ⅱ级[(0.51±0.18)pg/ml]、心功能Ⅲ级[(0.32±0.15)pg/ml]、心功能Ⅳ级[(0.18±0.10)pg/ml]依次降低,差异有统计学意义(P0.05);LVEF与血浆BNP、IL-27相关性分别为(r=-0.51,r=0.61,P0.05)。结论血浆BNP、IL-27水平变化均可反映CHF程度,而BNP表达的更为敏感,且两者之间有一定影响。     

Serum carboxy-terminal propeptide of type I procollagen (PIP) is a marker of diastolic dysfunction in patients with early type 2 diabetes mellitus

This study was designed to investigate whether the serum concentration of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of myocardial fibrosis, is related to changes of the ventricular filling dynamics in patients with early type 2 diabetes mellitus (T2DM). The T2DM group had lower mitral and tricuspid E/A ratios than the control group. Serum PIP was higher in patients with T2DM than in controls (131.1+/-45.6 vs. 109.3+/-32.5 ng/mL, p=0.039). A-Ar, an estimate of passive diastolic function, was inversely related to serum PIP levels in T2DM (r=-0.42, p=0.03). These results show a relation between LV diastolic function and serum PIP levels in early T2DM.     

Evaluation of impaired left ventricular ejection fraction and increased dimensions by multiple neurohumoral plasma concentrations.

BACKGROUND: A range of neurohumoral substances have been suggested as diagnostic markers in heart failure. It is, however, undetermined which marker has the greatest diagnostic potential, and whether additional information is gained by a comprehensive neurohumoral evaluation. AIMS: The purpose of the study was to compare the value of epinephrine, norepinephrine, renin activity, aldosterone (ALDO), atrial (ANP) and brain (BNP) natriuretic peptides, arginine-vasopressin and endothelin (ENDO) as markers for left ventricular (LV) dimensions and ejection fraction (LVEF) in patients with systolic heart failure. METHODS: Forty-eight patients with symptomatic heart failure were examined with blood samples and magnetic resonance imaging along with 20 age and gender-matched normal controls. RESULTS: In multiple regression analyses, BNP was the strongest independent marker for LV end-diastolic (r=0.71, P<0.0001), and end-systolic (r=0.75, P<0.0001) volumes, myocardial mass (r=0.69, P<0.0001), and LVEF (r=-0.78, P<0.0001). ANP was a supplementary independent marker for LV end-diastolic (r=0.76, P<0.0001) and end-systolic (r=0.78, P<0.0001) (ANP and BNP combined) volumes, ENDO for myocardial mass [r=0.71, P<0.0001 (ENDO/BNP)], and ALDO for LVEF [r=-0.81, P<0.0001 (ALDO/BNP)]. CONCLUSION: BNP is the strongest marker for LV dimensions and LVEF in patients with systolic heart failure. However, a comprehensive neurohumoral evaluation may add some information to the diagnosis.     

Plasma B-type natriuretic peptide reflects left ventricular hypertrophy and diastolic function in hypertension

BACKGROUND: Hypertension is associated with changes in concentrations of vasoactive peptides and procollagen propeptides, but their relationships with left ventricular hypertrophy and cardiac function are unclear. METHODS: We measured plasma levels of atrial natriuretic peptide (ANP), its amino terminal propeptide (NT-proANP), B-type natriuretic peptide (BNP), endothelin-1 (ET-1), and serum levels of the aminoterminal propeptide of type I procollagen (PINP) and the aminoterminal propeptide of type III procollagen (PIIINP) and echocardiographic parameters in 97 patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial. RESULTS: Median values (reference values) of the peptides were: ANP 11.2 (6.9-14.9) pmol/l, NT-proANP 351 (143-311) pmol/l, BNP 1.1 (0.4-7.2) pmol/l, ET-1 8.7 (1.2-5.0) pmol/l, PIIINP 2.8 (1.7-4.2) microg/l and PINP 29 (19-84) microg/l. Plasma BNP levels in patients with left ventricular hypertrophy (1.2 pmol/l) and patients with echocardiographic signs of diastolic dysfunction (1.5 pmol/l) were greater than those in patients without hypertrophy (0.7 pmol/l) and normal diastolic parameters (0.9 pmol/l) (p<0.05). BNP was the only biochemical parameter that independently predicted interventricular septal diastolic diameter (p<0.05), left ventricular mass index (p<0.01) and ratio of the velocity-time integrals of the E and A waves of the mitral inflow in a stepwise logistic regression analysis (p<0.05). CONCLUSIONS: The results show that BNP reflects the remodelling process in hypertension.     

Cardiac troponin T vs other biochemical markers in patients with congestive heart failure.

BACKGROUND: Several pathologic processes can cause myocardial injury, which is followed by cardiac remodeling and congestive heart failure (CHF). Cardiac troponin T (cTnT), a specific and sensitive marker of myocardial injury, has been related to long-term outcome in patients with CHF, so the relationship between cTnT and other biochemical markers associated with the pathophysiology of CHF was investigated in the present study. METHODS AND RESULTS: Between February 2004 and December 2005, 145 consecutive hospitalized patients (mean left ventricular ejection fraction (LVEF) 31.6+/-0.9%) with CHF were divided into low (<0.01 ng/ml) and high (> or =0.01 ng/ml) serum cTnT groups. Correlations with other prognostic biochemical markers, including brain natriuretic peptide (BNP), type I collagen C-terminal telopeptide (ICTP), procollagen type III peptide (PIIIP), renin, norepinephrine (NOREPI), C-reactive protein (CRP), cholesterol, hemoglobin (Hb), uric acid and HbA1c were examined. cTnT was high in 46 (32%) and low in 99 (68%) patients at baseline. Patients with high cTnT had abnormally high blood concentrations of BNP (p<0.0001), ICTP (p<0.0001), PIIIP (p=0.0006), NOREPI (p=0.0119), CRP (p=0.0003), uric acid (p=0.0026) and HbA1c (p=0.0361). In contrast, concentrations of cholesterol and Hb were significantly lower in patients with high cTnT (p=0.0319 and 0.0005, respectively). Death from or rehospitalization for CHF occurred in 41% in the high vs 9% in the low cTnT group (p=0.0002). Univariate analysis showed that high cTnT (p=0.0005), BNP (p=0.0001), renin (p=0.0158), NOREPI (p=0.0094), old age (p=0.0390), low LVEF (p=0.0231) and high New York Heart Association (NYHA) class (p=0.0006) were predictors of death from or rehospitalization for CHF. By multivariate analysis including BNP, NOREPI, age, LVEF and NYHA class, high cTnT and renin remained as significant predictors. CONCLUSIONS: Patients with ongoing myocardial injury and high cTnT had associated findings consistent with activation of the sympathetic system, synthesis of cardiac fibrosis, inflammation and metabolic abnormalities. By multivariate analysis, high cTnT and renin remained significant predictors of death or rehospitalization.