[Rare diseases from a life insurance perspective]. / Seltene Erkrankungen aus Sicht der Lebensversicherungswirtschaft.

A rare disease is defined as a disease that affects a maximum of 5 in 10,000 people. As of today there are roughly 7000 different rare diseases known. On account of this one can say that "rare diseases are rare, but people affected by them are common". For Germany this amounts to: 4 million people that are affected by a rare disease. Diagnosis, therapeutic options and prognosis have substantially improved for some of the rare diseases. Besides the general medical advances--especially in the area of genetics--this is also due to networking and sharing information by so-called Centres of Competence on a national and international scale. This results in a better medical care for the corresponding group of patients. Against this backdrop, the number of people applying for life assurance who are suffering from a complex or rare disease has risen steadily in the last years. Due to the scarce availability of data regarding long-term prognosis of many rare diseases, a biomathematical, medical and actuarial expertise on the part of the insurer is necessary in order to adequately assess the risk of mortality and morbidity. Furthermore there is quite a focus on the issue of rare diseases from not only politics but society as well. Therefore evidence based medical assessment by insurers is especially important in this group of applicants--thinking of legal compliance and reputational risk.

[Lone atrial fibrillation--relevance for medical underwriting]. / Idiopathisches Vorhofflimmern--Bedeutung in der medizinischen Risikoprüfung.

Atrial fibrillation is a common and multifaceted cardiac arrhythmia. At present rhythm and rate control can be considered equal regarding morbidity and mortality. Following scientific findings in the past years new therapeutic strategies and treatment options were developed. Therefore, a decision must be made not only between rate and rhythm control but also between the different antithrombotic drug regimes. Oral thrombin and factor X inhibitors herald a new era in antithrombotic therapy. The lack of necessity for routine INR monitoring certainly constitutes one of the greatest advantages of these novel agents in everyday clinical practice. Pulmonary vein isolation is a catheter-based treatment option for atrial fibrillation enabling the cure of arrhythmias for many patients--despite the high rate of recurrence. Many of these new therapeutical options lack long-term findings and previous successes are to be regarded with certain prudence.

[Evidence based risk assessment of coronary heart disease]. / Evidenzbasierte Risikoprüfung der Koronaren Herzerkrankung.

Coronary heart disease (CHD) poses a special challenge for risk assessments. Various kinds of diagnostic or therapeutic procedures, concomitant diseases, risk factors and symptoms need to be connected logically in order to assess the risk of each individual applicant. "Reinsurance manuals" are available to risk assessors in life insurance for this purpose. Using these manuals, the risk assessor can calculate the risk loadings for applicants with specific pre-existing conditions, e.g., CHD. Various tasks thus fall to the reinsurer, which must be able to give grounds for the increased risk loadings, provide the manuals with a process-oriented structure and simultaneously support the primary insurer's business objectives via an intelligent risk assessment. Taking CHD as an example, the following article explains how these tasks can be solved with the aid of medical and mathematical approaches, and how the insurability of applicants with CHD can be extended via the re-evaluation of risks.

QRS prolongation on surface ECG and brain natriuretic peptide as indicators of left ventricular systolic dysfunction.

OBJECTIVE: To determine whether the combination of prolonged QRS duration and brain natriuretic peptide (BNP) levels predicts left ventricular systolic dysfunction (LVSD) with a higher accuracy compared with QRS duration or BNP alone. SETTING: University hospital. METHODS: We studied 128 consecutive patients with suspected cardiac disease. At rest the QRS duration on 12-lead ECG and BNP levels were determined. A left ventricular ejection fraction (LVEF) <50% at echocardiography was defined as LVSD. RESULTS: QRS duration in the LVSD group (n = 66, LVEF 30 +/- 8%) was longer than in the group without LVSD (n = 62, LVEF 60 +/- 5%; QRS 129 +/- 34 vs. 96 +/- 20 ms, P < 0.001). BNP was higher in the LVSD group compared with controls (467 +/- 397 vs. 169 +/- 242 pg mL(-1), P < 0.001). A QRS duration of >0.1, >0.11 or >0.12 s was highly specific (63, 90 and 98%) but less sensitive (84, 81 and 75%) for the prediction of LVSD. A QRS cut-off value of 106 ms was moderately sensitive (65%) but very specific (87%) for the prediction of LVSD, whereas a BNP cut-off value of >84 pg mL(-1) was highly sensitive (89%) but only modestly specific (58%). The positive likelihood ratio for LVSD of abnormal BNP (2.0) and QRS prolongation >0.1 s (2.3) was improved by the combination of both criteria (5.1). In multivariate analysis, BNP and QRS duration were independent predictors of LVSD. CONCLUSIONS: The combination of abnormal BNP and QRS prolongation yields a higher positive likelihood ratio for the detection of LVSD compared with the two criteria alone.

Lower cardiac troponin T and I results in heparin-plasma than in serum.

BACKGROUND: The use of plasma rather than serum for determination of cardiac troponins can improve turnaround time and potentially avoid incomplete serum separation that may produce falsely increased results. We investigated the influence of incomplete serum separation and the effect of heparin-plasma on cardiac troponin concentrations. METHODS: Serum and heparin-plasma samples were drawn simultaneously from 100 patients (50 patients with acute coronary syndrome and 50 patients after open heart surgery) and measured on three different analytical systems, two for determination of cardiac troponin I (cTnI; Abbott AxSYM and Bayer ACS:Centaur) and one for cardiac troponin T (cTnT; Roche Elecsys cTnT STAT). Serum samples were reanalyzed after a second centrifugation to assess the influence of incomplete serum separation. RESULTS: Mean results (+/- 95% confidence interval) in heparin-plasma compared with serum were 101% +/- 2% (AxSYM cTnI), 94% +/- 3% (ACS:Centaur cTnI), and 99% +/- 3% (Elecsys cTnT). Differences >20% were seen in 11% of results on the ACS:Centaur, 9% of results on Elecsys cTnT, and 2% of results on the AxSYM. For the Elecsys cTnT assay, the magnitude of the difference between serum and plasma was independent of the absolute concentration and confined to individual samples, and was reversed by treatment with heparinase. A second centrifugation had no effect on serum results by any of the assays. CONCLUSION: The concentrations of troponins measured in heparin-plasma are markedly lower than in serum in some cases.

Changes of beta-adrenergic signaling in compensated human cardiac hypertrophy depend on the underlying disease.

In human heart failure, desensitization of the beta-adrenergic signal transduction has been reported to be one of the main pathophysiological alterations. However, data on the beta-adrenergic system in human compensated cardiac hypertrophy are very limited. Therefore, we studied the myocardial beta-adrenergic signaling in patients suffering from hypertrophic obstructive cardiomyopathy (HOCM, n = 9) or from aortic valve stenosis (AoSt, n = 8). beta-Adrenoceptor density determined by [(125)I]iodocyanopindolol binding was reduced in HOCM and AoSt compared with nonhypertrophied, nonfailing myocardium (NF) of seven organ donors. In HOCM the protein expression of stimulatory G protein alpha-subunit (G(s)alpha) measured by immunoblotting was unchanged, whereas the inhibitory G protein alpha-subunit (Galpha(i-2)) was increased. In contrast, in AoSt, Galpha(i-2) protein was unchanged, but G(s)alpha protein was increased. Adenylyl cyclase stimulation by isoproterenol was reduced in HOCM but not in AoSt. Plasma catecholamine levels were normal in all patients. In conclusion, both forms of hypertrophy are associated with beta-adrenoceptor downregulation but with different changes at the G protein level that occur before symptomatic heart failure due to progressive dilatation of the left ventricle develops and are not due to elevated plasma catecholamine levels.