Long-term treatment with supraphysiologic doses of levothyroxine in treatment-refractory mood disorders - A prospective study of cardiovascular tolerability.

BACKGROUND: To investigate long-term effects of adjunctive prophylactic treatment with supraphysiologic doses of levothyroxine (L-T4) on cardiovascular tolerability in 23 patients with treatment-refractory mood disorders. METHODS: Starting point for a comprehensive cardiovascular assessment in patients was the indication for long-term maintenance treatment with L-T4 (mean dose 463 mcg/day). Prospective longitudinal assessment of the cardiovascular risk profile included in addition to a physical examination and blood pressure measurement, several technical investigations: resting electrocardiogram, transthoracic echocardiogram, cardiac stress test, and holter electrocardiogram. Statistical analysis was performed by linear mixed effects models (LMM) for evaluation of longitudinal changes in various heart measures. RESULTS: During the mean observational period of 20.4 months none of the heart measures reached statistical significance in change over time. None of the assessed cardiac parameters of each single patient was in a range predictive for cardiac dysfunction. LIMITATIONS: Small sample size, no technical cardiac investigations prior to L-T4 initiation, no patient control group with mood disorders who did not receive L-T4. CONCLUSIONS: Results of this study indicated no increased risk for cardiovascular disorders during treatment with supraphysiologic L-T4 doses in patients with refractory mood disorders.

Usefulness of detectable levels of troponin, below the 99th percentile of the normal range, as a clue to the presence of underlying coronary artery disease.

The aim of the study was to evaluate whether markers of myocardial injury and ischemia are helpful in detecting coronary artery disease (CAD) in patients with stable angina. Venous blood was obtained before and after a bicycle exercise test in 47 outpatients with suspected CAD for measurement of cardiac troponin I (cTnI), heart-type fatty acid binding protein, and glycogen phosphorylase BB. Patients with a coronary artery stenosis >/=70% in diameter (n = 33) were compared with patients with coronary narrowing <50% (controls, n = 14). None of the markers increased after bicycle exercise testing. cTnI measured before and after exercise was higher in the CAD group than in controls (p <0.001). The area under the curve for diagnosis was greater when the cTnI value was detectable than with stress testing alone. In conclusion, baseline cTnI was of value in detecting CAD and also during follow-up in predicting the need for further revascularization.

Pregnancy-associated plasma protein A values in patients with stable cardiovascular disease: use of a new monoclonal antibody-based assay.

BACKGROUND: PAPP-A is promising in improving risk stratification and invasive treatment decisions in stable cardiovascular patients. We evaluated the prognostic value of pregnancy-associated plasma protein A (PAPP-A) measured by a novel assay in stable cardiovascular patients. METHODS: We investigated 228 stable cardiovascular outpatients. Blood was drawn for PAPP-A measurement after echocardiography and ergometry prior to heart catheterization. Angiographically we determined severity as well as qualitative characteristics suspect for vulnerability of coronary lesions. After 1108±297 days, follow-up information was obtained by questionnaire mailings and interviews by phone. RESULTS: 104 patients had coronary stenosis≥70%, 75 had B-type lesions≥50%, 46 showed complex lesions, and 68 were suspected to have vulnerable lesions. Median PAPP-A was 1.76 (interquartile range 1.21, 2.63) µIU/ml in the entire cohort. PAPP-A concentrations did not differ in dependence on coronary artery findings. A cutpoint of 2.7 µIU/ml was derived from receiver-operator characteristics for outcome measures. For this cutoff, Cox proportional hazard models with 19 further clinical variables showed that PAPP-A was predictive for all-cause death (HR 4.73, 95% CI 1.46-15.31, p=0.01), all-cause death or nonfatal infarction (HR 4.01, 95% CI 1.58-10.13, p=0.003) and all-cause death, nonfatal myocardial infarction or hospitalization (HR 1.96, 95% CI 1.03-3.70, p=0.04). The predictive value of PAPP-A did not change substantially after correction for values of cardiac troponin, using a highly sensitive cardiac troponin I research assay. CONCLUSIONS: PAPP-A, measured by a new, monoclonal antibody-based assay is a promising prognostic marker in patients with stable cardiovascular disease and an indication for heart catheterization.