Digital mammography screening: sensitivity of the programme dependent on breast density.

OBJECTIVES: To analyse the impact of breast density on the sensitivity of a population-based digital mammography screening programme (SP) as key evaluation parameter. METHODS: 25,576 examinations were prospectively stratified from ACR category 1 to 4 for increments of 25 % density during independent double reading. SP was calculated as number of screen-detected cancers divided by the sum of screen-detected plus interval cancers (24-months period) per ACR category, related to the first reading (a), second reading (b) and highest stratification if discrepant (c). Chi-square tests were used for comparison. RESULTS: Overall sensitivity of the programme was 79.9 %. SP in ACR 4 (a: 50 %, b: 50 %, c: 50 %) was significantly lower than in ACR 3 (a: 72.9 %, b: 79.4 %, c: 80.7 %, p < 0.001), ACR 2 (a: 83.9 %, b: 85.7 %, c: 83.2 %, p < 0.001) and ACR 1 (a: 100 %, b: 88.8 %, c: 100 %; p < 0.001). Frequencies of ACR 4 were a: 5.0 %, b: 4.3 %, c: 6.9 %. CONCLUSION: Digital mammography screening with independent double reading leads to a high overall SP. In the small group of women with breast density classified as ACR 4 SP is significantly reduced compared to all other ACR categories. KEY POINTS: • Overall sensitivity of a population-based digital mammography screening programme (SP) was 79.9 %. • In women with ACR 1, 2, or 3, SP ranged between 72.9 %-100 %. • ACR 4 was rare in participants (<7 %) and SP was only 50 %. • SP in ACR 4 differed significantly from ACR 3 (p < 0.001).

[Adherence to Long-term Follow-up in Paediatric Oncology--Results of a Monocentric Analysis]. / Nachsorgeadhärenz in der Pädiatrischen Onkologie - Ergebnisse einer monozentrischen Analyse.

BACKGROUND: Cured paediatric-oncology patients frequently present with health problems even years after treatment. Hence long-term follow-up (LTFU) is essential. This analysis tries to identify factors that influence regular LTFU attendance. STUDY POPULATION: Between 1991 and 2010, 2 153 children and adolescents were treated at Muenster University Department of Paediatric Hematology and Oncology (UKM). 1 708 patients with permanent residence in Germany and completed therapy have been included into this analysis. METHODS: Patients were reviewed for the duration and regularity of LTFU at UKM. Prospective analyses with postponed starting-points have been conducted as well as descriptive analyses to validate correlations. Prospective data were evaluated by Kaplan-Meier-Analyses, the analysis of multivariate correlations by Cox Proportional Hazard Model. RESULTS: 2 years after the end of therapy 83% of the patients were still in LTFU. After 5 and 10 years this percentage decreased to 67 and 42%. Patients diagnosed after the year 2000 and younger patients attended LTFU for a longer period (p<0,005). There were no significant gender differences. Statutory insured patients stayed longer in LTFU than private health insured (p<0,005). The multivariate examination showed only small differences between systemic diseases and solid tumours. The residential distance had no significant influence. CONCLUSIONS: Younger, more recently treated and statutory insured patients showed a significantly longer LTFU.

[Who Hits the Mark? A Comparative Study of the Free Geocoding Services of Google and OpenStreetMap]. / Wer trifft ins Schwarze? Ein qualitativer Vergleich der kostenfreien Geokodierungsdienste von Google und OpenStreetMap.

BACKGROUND: Geocoding, the process of converting textual information (addresses) into geographic coordinates is increasingly used in public health/epidemiological research and practice. To date, little attention has been paid to geocoding quality and its impact on different types of spatially-related health studies. The primary aim of this study was to compare 2 freely available geocoding services (Google and OpenStreetMap) with regard to matching rate (percentage of address records capable of being geocoded) and positional accuracy (distance between geocodes and the ground truth locations). METHODS: Residential addresses were geocoded by the NRW state office for information and technology and were considered as reference data (gold standard). The gold standard included the coordinates, the quality of the addresses (4 categories), and a binary urbanity indicator based on the CORINE land cover data. 2 500 addresses were randomly sampled after stratification for address quality and urbanity indicator (approximately 20 000 addresses). These address samples were geocoded using the geocoding services from Google and OSM. RESULTS: In general, both geocoding services showed a decrease in the matching rate with decreasing address quality and urbanity. Google showed consistently a higher completeness than OSM (>93 vs. >82%). Also, the cartographic confounding between urban and rural regions was less distinct with Google's geocoding API. Regarding the positional accuracy of the geo-coordinates, Google also showed the smallest deviations from the reference coordinates, with a median of <9 vs. <175.8 m. The cumulative density function derived from the positional accuracy showed for Google that nearly 95% and for OSM 50% of the addresses were geocoded within <50 m of their reference coordinates. CONCLUSION: The geocoding API from Google is superior to OSM regarding completeness and positional accuracy of the geocoded addresses. On the other hand, Google has several restrictions, such as the limitation of the requests to 2 500 addresses per 24 h and the presentation of the results exclusively on Google Maps, which may complicate the use for scientific purposes.

[Evaluation of the impact of the mammography screening program on breast cancer mortality: feasibility study on linking several data sources in North Rhine-Westphalia]. / Evaluation der Auswirkungen des Mammographie-Screening-Programms auf die Brustkrebsmortalität : Machbarkeitsstudie zur Verknüpfung verschiedener Datenquellen in Nordrhein-Westfalen.

BACKGROUND: In the German Mammography Screening Program (MSP), women aged 50-69 years are offered X-ray-based mammography for the early detection of breast cancer (BC) every 2nd year. To maintain the licensing of the MSP, evidence of a positive benefit-risk assessment of the radiation-related health risk has to be provided. Therefore, long-term effects of the program have to be shown by evaluating the BC mortality reduction based on the MSP. A current feasibility study attempts to develop different data flow models to evaluate whether, based on current legislations on data confidentiality, secondary data routinely available in the German health system can be linked in such a way that they can be used for epidemiological evaluation studies. We present the"NRW model," which builds on procedures developed and evaluated in the Epidemiological Cancer Registry of North Rhine-Westphalia (EKR-NRW). METHODS: Data of the Association of Statutory Health Physicians in Westfalen-Lippe (KVWL) are used to enumerate the cohort of women in WL who are entitled to MSP participation and their use of curative mammography outside of the MSP. The EKR-NRW provides epidemiological and medical data on all BC cases in WL, on cohort mortality, and on causes of death. The central MSP database MaSc offers the screening history of all MSP participants. The established uniform encryption methods employed in the EKR-NRW are used for linking records from the three data sources in one data-merging center (DZS). To this end, data are first captured in standardized formats, variably aggregated and transferred in an encrypted format, checked for anonymity and diversity level in an encrypted form, and eventually stored in a factually anonymized manner in the evaluation center (ES). Researchers can obtain data sets with plain text epidemiological-medical data from the ES for analyses.

[Cohort study of cancer incidence in patients with type 2 diabetes: record linkage of encrypted data from an external cohort with data from the epidemiological Cancer Registry of North Rhine-Westphalia]. / Kohortenstudie zur Krebsinzidenz bei Patienten mit Diabetes mellitus Typ 2 : Record Linkage von kryptografierten Daten einer externen Kohorte mit Daten des Epidemiologischen Krebsregisters Nordrhein-Westfalen.

INTRODUCTION: German epidemiologic cancer registries may store only encrypted personal identifiers. Thus, record linkage with secondary databases needs to be performed via procedures that are based on encrypted identifiers. In this paper, we describe the linkage of patient data from a statutory health insurance company (AOK NordWest) and from the Disease Management Program for diabetes mellitus type 2 with the database of the cancer registry. We report the cancer incidence in patients with type 2 diabetes (T2D). METHODS: Personal identifying variables of the patient cohort were encrypted before being sent electronically to the cancer registry and submitted to a probabilistic record linkage with registry data. The study included T2D patients who were residents of the Münster, Detmold, or Arnsberg districts and who were aged 40-79 years. Only primary cancers occurring between the date of enrolment and the censoring date (31 December 2010) were included. The standardized incidence ratio (SIR) was calculated relative to the number of incident cases expected on the basis of the averaged incidence rates in the general population. RESULTS: The record linkage took about 3 weeks of processing time. A total of 67,447 T2D (49.2 % men) cases were included for analyses. Incident cancer was diagnosed in 2,086 men and 1,578 women. Cohort members showed an elevated risk for cancer of the liver (SIR =1.86; 95% CI =1.47-2.31), pancreas (SIR = 1.62; 95 % CI =1.36-1.91), lung (SIR = 1.21; 95% CI 1.11-1.32), and uterus (SIR = 1.34; 95 % CI 1.08-1.65), and they were less likely to be diagnosed with prostate cancer (SIR =0.72; 95% CI = 0.65-0.79). DISCUSSION: The findings of this study suggest that record linkage of secondary databases with cancer registry data for research purposes can be effectively carried out in compliance with strict data-protection regulations.

Cancer detection rates following enrolment in a disease management programme for type 2 diabetes.

AIMS/HYPOTHESIS: Recent prospective studies found an elevated cancer risk shortly after diabetes diagnosis, and this was probably due to increased ascertainment. This study investigated whether site-specific cancer risks are also raised following enrolment in a disease management programme for type 2 diabetes mellitus (DMP-DM2). METHODS: We linked records from a DMP-DM2 to population cancer registry data. The study period was from June 2003 to December 2009. Standardised incidence ratios (SIRs) were calculated for time intervals following DMP enrolment using the cancer incidence rates of the general source population. Additionally, Poisson regression with natural splines was used to assess time-dependent cancer incidence by diabetes duration. RESULTS: There were 2,034 first invasive cancer cases identified over 163,738 person-years of follow-up. Pancreatic cancer risk was significantly increased mainly in the first year after enrolment (SIR 1.62); the increment was only seen for patients in whom diabetes had been diagnosed less than 1 year before DMP-DM2 enrolment. Risk of endometrial cancer was similarly raised in the first year after DMP-DM2 enrolment among individuals newly diagnosed with diabetes but decreased rapidly thereafter. There was no time dependence in the incidence of cancers of the liver, lung, colon, breast and prostate. CONCLUSIONS/INTERPRETATION: Enrolment in a DMP-DM2 did not appear to induce ascertainment bias for most cancers. Cancer risks were initially increased, especially for pancreatic cancer, potentially as a result of reverse causality. Ascertainment bias and time-dependent incidence of cancer appear to be less of a problem in settings using DMP-like structures for the study of the association between diabetes duration, glucose-lowering medication and cancer incidence.

[Data quality or differences in oncological care? - standards of reporting for cancer survival analyses based on registry data]. / Datenqualität oder Unterschiede in der onkologischen Versorgung? - Berichtsstandards für Überlebenszeitanalysen mit Krebsregisterdaten.

BACKGROUND: The results of population-based cancer survival analyses are essential criteria with regard to the evaluation of oncological care. Their use and their interpretation as such require knowledge and transparency with regard to the data basis in order to avoid inadequate conclusions. METHOD: The working group 'survival analysis' of the Association of Population-Based Cancer Registries in Germany (GEKID) has identified factors within cancer registration and data evaluation which may distort population-based cancer survival analyses to a relevant degree. Recommendations in terms of standards of reporting were developed by mutual consent following empirical studies and discussions within GEKID. RESULTS: We provide a list of 17 indicators to be taken into account and to be presented within the scope of population-based survival analyses. CONCLUSIONS: Referring to the "standards of reporting concerning population-based cancer survival analyses" introduced by GEKID there is a proposal on data transparency on hand, which might contribute substantially to the assessability of outcome quality in oncological care.

[Development and first results of fast and cost-effective examination methods for an ophthalmological screening within the National Cohort]. / Entwicklung und erste Anwendungserfahrungen einer schnellen und kostengünstigen ophthalmologischen Untersuchung für die Nationale Kohorte.

BACKGROUND: For an implemented ophthalmological screening within a German long-term cohort study (National Cohort) simple and effective methods for an examination of visual acuity and for non-mydriatic retina photografies should be evaluated. Furthermore standard operating-procedures (SOP) should be developed. METHODS: In the years 2011 and 2012 pinhole visual acuity measurements and automated retina photographies (DRS, CenterVue S. p. a., Padua, Italy) were made at three different epidemiological study centers within Germany. Furthermore, anterior segment images were taken by the camera. Standard operating procedures (SOP) regarding the ophthalmological screening were developed and evaluated within the study. The main question was whether it is possible to implement the screening methods within the National Cohort. Further main outcomes were quality and interpretability of the taken images. RESULTS: 457 subjects (914 eyes) were examined within the investigation. Median VA was 0.8 for right and left eyes (p > 0.42). Image quality of the photographies was good in 491 cases (54 %), fair in 239 cases (26 %) and bad in 179 cases (20 %). The usability of the images was without limitations in 686 cases (75 %), limited in 152 cases (17 %) and not given in 71 cases (8 %). Increasing age of the subjects was slightly correlated with decreasing image quality (r = 0.26) and decreasing image usability (r = 0.2). Anterior segment photographies were usable in 176 eyes (56 %). CONCLUSION: The developed screening method fulfilled the specifications of the National Cohort. The used pinhole visual acuity examination was fast and cheap. Image quality and usability of the retina photographies could be improved with prolonged pupil recovery times. The quality of the anterior segment images could not fulfill the expectations and were taken out of the further examinations of the ophthalmological screening. The written SOP showed good acceptance within the investigators' daily routine. The ophthalmological screening within the National Cohort generates information (e. g., pathologies of the vessels or of the retina) which are useful not only from an ophthalmological point of view.

[Linkage of secondary data with cancer registry data on the basis of encrypted personal identifiers - results from a pilot study in North Rhine-Westphalia]. / Abgleich von Sekundärdaten mit einem epidemiologischen Krebsregister auf der Basis verschlüsselter Personendaten - Ergebnisse einer Pilotstudie in Nordrhein-Westfalen.

BACKGROUND: The Cancer Registry of North-Rhine-Westphalia stores exclusively encrypted personal identifiers of registered cancer patients. Therefore, comparisons with secondary data sets can only be performed by record linkage procedures that are based on encrypted personal identifiers. We report on a pilot study which linked encrypted personal data from the disease management program for patients with diabetes mellitus type 2 (DMP-DM2) with the database of the EKR NRW in order to test the feasibility and efficiency of these record linkage procedures. METHODS: Personal identifying variables of the DMP records were encrypted in a 2-stage process before being sent electronically to the EKR NRW where they were subsequently submitted to a probabilistic record linkage with the registry data. The study included 27 450 participants who were insured at the AOK NordWest, residents of the district Münster and who were aged 40-79 years at the time of first enrolment to the DMP-DM2 between June 2003-July 2008. RESULTS: The electronic processing time of the semi-automatic record linkage procedure took about 24 h. Approximately 2% of the records had to be reviewed manually. After exclusion of prevalent cancer cases, multiple primaries and inadequate data, 26 742 participants (47.3% men; 52.7% women) remained in the data set. About 1 364 cohort members (759 men, 605 women) were diagnosed with cancer after submission to the disease management program. DISCUSSION: The DMP-DM2 records were encrypted and linked to cancer registry data with a moderate personnel and financial input and high efficiency. Linked records were instantly usable for epidemiological analyses. Experiences of the pilot study suggest that future linkage studies can further advance the level of data protection, without losses in efficiency, by moderately complex software modifications and amendments of the data flow.

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: the MONICA/KORA Augsburg cohort study.

BACKGROUND AND AIM: It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. METHODS AND RESULTS: We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n=833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n=36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n=21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). CONCLUSIONS: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes.

Prevalence of congenital heart defects in newborns in Germany: Results of the first registration year of the PAN Study (July 2006 to June 2007).

OBJECTIVE: To investigate the current prevalence of congenital heart defects (CHD) in live births in Germany and to assess its relation to demographic and gestational parameters. DESIGN: Nation-wide study (PAN: Praevalenz angeborener Herzfehler bei Neugeborenen) with passive registration of infants born between 1st July 2006 and 30th June 2007 in Germany diagnosed with CHD. RESULTS: Data were provided by 260 participating institutions. 7 245 infants with CHD were registered to give a total CHD prevalence of 1.08%. The most common lesions were: ventricular septal defect (all types) (48.9%), atrial septal defect (17.0%), valvular pulmonary stenosis (6.1%), persistent arterial duct (4.3%) and aortic coarctation (3.6%). The most common cyanotic lesions were tetralogy of Fallot (2.5%) and complete transposition of the great arteries (2.2%). A single ventricle (all types) was identified in 2.8%, half of them being a hypoplastic left heart syndrome. Female gender was more common among mild CHD (57.3%) while there was a striking predominance of male infants among severe lesions (58.4%). Prematurity (18.7% vs. 9.1%), a birth weight below 2 500 g (17.5% vs. 6.8%) and multiple births (6.2% vs. 3.3%) were more frequent in infants with CHD than in all live births. More than 80% of the CHD diagnoses were made within three months after birth. CONCLUSIONS: The PAN study recorded an overall CHD prevalence of 1.08% in Germany. The proportion of mild CHD may indicate a high diagnostic level, the prevalence of severe lesions is concordant with ranges reported by others. CHD is associated with prematurity, low birth weight and multiple births.

[Epidemiology of prostate cancer: recent results from the Epidemiological Cancer Register of the District of Münster (Germany)]. / Aktuelle Daten zur Epidemiologie des Prostatakarzinoms : Ergebnisse aus dem Regierungsbezirk Münster.

BACKGROUND: Prostate cancer is characterized by worldwide increasing incidence rates, improved survival, and decreasing mortality. We investigated the current situation in the Epidemiological Cancer Register of the District of Münster, Germany (which has approximately 1.25 million male inhabitants). MATERIALS AND METHODS: We calculated the incidence and mortality rates, stage distribution, and relative survival rates for prostate cancer between the years 2002 and 2004. RESULTS: The age-standardized incidence rate was 115/100,000 men per year, and the median age at diagnosis was 70 years. The tumour stage was T1/T2 in 69.6% of cases. The estimated relative survival after 5 years was 83.5% (95% confidence interval 81.4-85.4) and after 10 years was 73.3% (69.5-77.0). Survival was barely affected when the tumour was limited to the prostate (UICC I-II), whereas survival rates were markedly reduced when the tumour had spread or had infiltrated adjacent structures (UICC IV; relative 10-year survival rate 22.1%). CONCLUSIONS: The majority of patients with prostate cancer now have a favourable prognosis. Increased incidence rates must be interpreted in the context of widespread use of prostate-specific antigen testing.

[Practice of early detection of prostate cancer : Descriptive survey in preparation for the PSAInForm study]. / Praxis der Früherkennung des Prostatakarzinoms : Deskriptive Erhebung im Vorfeld der PSAInForm-Studie.

BACKGROUND: The randomized controlled PSAInForm study aims to investigate the effects of a computer-based decision aid which informs men in the age group 55-69 years about advantages and disadvantages of PSA testing. In preparation for the study, the current PSA testing practice in the Münster district was assessed. MATERIALS AND METHODS: The frequencies of early detection examinations, medically indicated PSA tests, and prostate biopsies in the Münster district were determined, using aggregated data from the regional association of Statutory Health Insurance (SHI) Physicians in Westfalen-Lippe. With anonymized laboratory data, the frequency of PSA tests in general and urological practices, and their distribution among the accounting categories SHI, individual health services, and invoices for privately insured patients were investigated. RESULTS: In about half of more than 50,000 PSA tests, the accounting category could be determined; the rest could only be assigned to SHI or non-SHI services. The percentage of PSA tests that were performed due to reasons other than medically necessary SHI-reimbursed services was > 50% in each age group; it was highest in men younger than 55 years, and declined markedly with advanced age. More than half of the PSA tests that were likely due to opportunistic screening were performed outside the age group 55-69 years. CONCLUSIONS: The percentage of PSA tests that were not carried out as SHI services was > 80% in general practices, and 60% in urological practices. These percentages decreased markedly with advancing age. Most of the PSA tests were performed outside the age group which can be considered as the target group for an effective PSA screening according to the results of the European Randomized study of Screening for Prostate Cancer (ERSPC).

Ankle-brachial index and peripheral artery disease are not related to restless legs syndrome.

OBJECTIVE: Our aim was to investigate the relationship between impaired peripheral arterial circulation as measured by ankle-brachial index (ABI) and restless legs syndrome (RLS) in the general population. METHODS: Data are derived from three independent, German population-based, prospective studies: the control sample of BiDirect (N = 966), the second follow-up of SHIP (N = 2333), and a subsample of SHIP-Trend (N = 1269). RLS was assessed with questions based on the RLS minimal criteria. ABI was measured with an automated method in BiDirect and with Doppler ultrasound in both SHIP studies. An ABI score below 0.9 was indicative of peripheral arterial disease (PAD). Co-morbidities, medications and behavioural factors were self-reported. Additional measurements included body mass index and haemoglobin from blood serum. For BiDirect, a follow-up with identical methodology was performed after a median of 2.5 years. RESULTS: In cross-sectional analyses, decreased ABI was not significantly associated with RLS as outcome in multivariable logistic regression models adjusted for several potential confounders (BiDirect: odds ratio (OR) = 1.07 for a -0.1 change in ABI, 95% confidence interval (CI): 0.81-1.42, p = 0.62; SHIP-2: OR = 0.99, CI: 0.85-1.16, p = 0.94; SHIP-Trend: OR = 0.99, CI: 0.87-1.13, p = 0.88). Similar non-significant results were achieved using PAD (instead of ABI) as an independent variable. In BiDirect, baseline ABI was not a significant predictor of incident RLS in longitudinal analysis (OR = 0.77, CI: 0.53-1.12, p = 0.17). CONCLUSION: Results from three independent studies suggest that reduced ABI is not a risk factor for RLS in the general population.

Reduction of Advanced Breast Cancer Stages at Subsequent Participation in Mammography Screening.

PURPOSE: The decline in advanced breast cancer stages is presumably the most relevant surrogate parameter in mammography screening. It represents the last step in the causal cascade that is expected to affect breast cancer-related mortality. To assess the effectiveness of population-based screening, we analyzed the 2-year incidence rates of advanced breast cancers between women participating in the initial and in the first subsequent round. MATERIALS AND METHODS: The study included data from 19,563 initial and 18,034 subsequent examinations of one digital screening unit (2008 - 2010). Data on tumor stages, detected by screening or within the following interval of two years (2-year incidence), were provided by the epidemiological cancer registry. Rates of all and combined UICC stages 2, 3 and 4 (advanced stages) were reported for a two-year period. Proportions were tested for significance by using chi-square tests (p < 0.001). RESULTS: The 2-year incidence rate of all stages was significantly lower in participants in subsequent screening than in initial screening (0.85 vs. 1.29 per 100 women (%); p < 0.0001). A significantly lower 2-year incidence of advanced stages was observed for subsequent screening compared to initial screening (0.26 % vs. 0.48 %; p = 0.0007). Among women aged 50 to 59 years, the incidence of advanced stages was less clearly different (0.21 % vs. 0.35 %; p = 0.07) than in women aged 60 to 69 years (0.31 % vs. 0.70 %; p = 0.0008). CONCLUSION: During the change from prevalent to incident phase mammography screening, a program impact is seen by a lower 2-year incidence of advanced breast cancers within subsequent compared to initial participants, predominately in women aged 60 to 69 years. KEY POINTS: • The incidence of advanced tumor stages represents the most relevant surrogate parameter for screening effectiveness. • For the first time the 2-year incidence of advanced breast cancer stages after subsequent mammography screening was analyzed. • We observed a significant effect of screening on the 2-year incidence of advanced stages, predominately in the age group 60 to 69 years.

Body composition and prevalence of left ventricular hypertrophy.

BACKGROUND: Fat-free mass (FFM) has been proposed as an optimal normalization of left ventricular (LV) mass to body size. We sought to evaluate the novel FFM-based criteria of LV hypertrophy (LVH). METHODS AND RESULTS: A population sample of 1371 men and women aged 25 to 74 years was examined by echocardiography and bioelectrical impedance analysis. Internal partition values for LVH were generated in a healthy population subgroup on the basis of LV mass divided by FFM and by the traditional indexations to body height, height(2.7), and body surface area. In contrast to the sex-specific criteria required by traditional indexations, the value of LV mass/FFM that divided individuals with and without LVH was identical for men and women (4.1 g/kg). Estimates of LVH prevalence varied significantly by type of indexation used, internally or externally derived cut points, and by population subgroups. Differences were pronounced among hypertensives and the obese. Thus, the application of LV mass/FFM more than halved the risk of LVH in obese versus nonobese women (odds ratio, 2.5; 95% confidence interval, 1.6 to 4.0) compared with criteria based on LV mass/height(2.7) (odds ratio, 5.5; 95% confidence interval, 3.6 to 8.3). Implications among hypertensives were less marked. CONCLUSIONS: Indexation of LV mass to FFM eliminates sex-specific LVH criteria. The proportion of individuals defined as having LVH using the new criteria deviate markedly from traditional indexations. Prospective investigations will be needed to identify the prognostic implications of different indexations, especially in subgroups such as the obese.

Lack of association between a polymorphism of the aldosterone synthase gene and left ventricular structure.

BACKGROUND: Cardiac growth and function may be modulated in part by trophic effects of neurohormones. Specifically, aldosterone has been shown to stimulate the growth of cardiac myocytes and the accumulation of cardiac extracellular matrix proteins. Moreover, a variant of the aldosterone synthase gene (a cytosine/thymidine exchange at position -344 in the transcriptional regulatory region) has been associated with enlargement and disturbed filling of the left ventricle (LV) in a small sample of young white adults. The aim of the present study was to reinvestigate the implications of aldosterone synthase -344C/T allele status for serum aldosterone levels, blood pressure, and LV structure and function in large population-based samples. METHODS AND RESULTS: Individuals who participated in the echocardiographic substudy of the third MONICA (MONitoring trends and determinants in CArdiovascular disease) survey (n=1445) or in the second follow-up of the first MONICA survey (n=562) were studied by standardized anthropometric, echocardiographic, and biochemical measurements as well as genotyping for aldosterone synthase -344C/T allele status. In both surveys, the distribution of sex, age, arterial blood pressure, and body mass index was homogeneous in the aldosterone synthase genotype groups. Echocardiographic LV wall thicknesses, dimensions, and mass indexes were not significantly associated with a specific aldosterone synthase genotype. Likewise, no association was detectable with echocardiographic measures of LV systolic or diastolic function. Data were consistent in both samples and not materially different in subgroups defined by age, sex, or intake of antihypertensive medication. Finally, no significant association was observed for aldosterone synthase allele status and serum aldosterone levels in the group of 562 individuals. CONCLUSIONS: The data are not in favor of a significant contribution of the C/T exchange at position -344 in the aldosterone synthase transcriptional regulatory region to the variability of serum aldosterone levels, blood pressure, or cardiac size or function as found in 2 white population-based samples.

Augmentation of the cardiac natriuretic peptides by beta-receptor antagonism: evidence from a population-based study.

OBJECTIVES: The present retrospective analysis of data derived from a population-based study examined the relationship between intake of beta-receptor antagonists and plasma concentrations of the cardiac natriuretic peptides and their second messenger. BACKGROUND: Beta-receptor antagonists are widely used for treatment of cardiovascular disease. In addition to direct effects on heart rate and cardiac contractility, recent evidence suggests that beta-receptor antagonists may also modulate the cross talk between the sympathetic nervous system and the cardiac natriuretic peptide system. METHODS: Plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and their second messenger cyclic guanosine monophosphate (cGMP) were assessed in addition to anthropometric, hemodynamic and echocardiographic parameters in a population-based sample (n = 672), of which 80 subjects used beta-receptor antagonists. RESULTS: Compared to subjects without medication, subjects receiving beta-receptor antagonists were characterized by substantially elevated ANP, BNP and cGMP plasma concentrations (plus 32%, 89% and 18%, respectively, p < 0.01 each). Analysis of subgroups revealed that this effect was highly consistent and present even in the absence of hypertension, left atrial enlargement, left ventricular hypertrophy or left ventricular dysfunction. The most prominent increase was observed in a subgroup with increased left ventricular mass index. By multivariate analysis, a statistically significant and independent association between beta-receptor antagonism and ANP, BNP and cGMP concentrations was confirmed. Such an association could not be demonstrated for other antihypertensive agents such as angiotensin-converting enzyme inhibitors or diuretics. CONCLUSIONS: Beta-receptor antagonists appear to augment plasma ANP, BNP and cGMP concentrations. The current observation suggests an important contribution of the cardiac natriuretic peptide system to the therapeutic mechanism of beta-receptor antagonists.

Familial predisposition of left ventricular hypertrophy.

OBJECTIVES: The study evaluated the contribution of familial predisposition to the risk of left ventricular hypertrophy (LVH). BACKGROUND: Left ventricular hypertrophy is a multifactorial condition that serves as an important predictor of cardiovascular mortality. At present it is unclear whether familial predisposition contributes to the manifestation of LVH. Thus, we determined whether siblings of subjects with LVH are at increased risk to present with an elevation of LV mass or an abnormal LV geometry. METHODS: Echocardiographic and anthropometric measurements were performed in 2,293 individuals who participated in the echocardiographic substudies of population-based MONICA Augsburg surveys. In addition, a total of 319 siblings of survey participants with echocardiographic evidence of LVH were evaluated. The risk of these siblings to present with LVH or abnormal LV geometry was estimated by comparison with 636 subjects matched for gender and age that were selected from the entire echocardiography study base. RESULTS: Blood pressure, body mass index, age, and gender (i.e., known determinants of LV mass) were comparable in LVH-siblings and the matched comparison group. However, septal and posterior wall thicknesses, relative wall thickness as well as LV mass index were significantly elevated in LVH-siblings (p < 0.001, each) whereas LV dimensions did not differ. Likewise, the prevalence of LVH was raised in LVH-siblings, as was the relative risk of LVH after adjustment for confounders (p < 0.05). More specifically, LVH-siblings displayed increased prevalences of concentric remodeling and concentric LVH (p < 0.05) but not of eccentric LVH. CONCLUSIONS: Familial predisposition appears to contribute to increased LV wall thickness, to the development of LV hypertrophy and abnormal LV geometry.

The associations of body size and body composition with left ventricular mass: impacts for indexation in adults.

OBJECTIVES: We investigated the relationship between body size, body composition and left ventricular mass (LVM) in adults, and assessed the impact of different indexations of LVM on its associations with gender, adiposity and blood pressure. BACKGROUND: The best way to normalize LVM for body size to appropriately distinguish physiologic adaptation from morbid heart morphology was discussed. METHODS: We undertook a community survey of 653 men and 718 women, aged 25 to 74 years. Lean body mass (LBM) was determined by bioelectric impedance analyses and LVM was assessed by two-dimensional guided M-mode echocardiography. RESULTS: After traditional indexations to body height, body height2.7, or body surface area, men had higher LVM than women (p < 0.001). These gender differences disappeared (p > 0.05) when LVM was indexed to LBM. The type of indexation also modified the strength of the association between adiposity and LVM. The estimated impact of body fat on LVM indexed to LBM was less than half that obtained with traditional indexations. In contrast, the magnitude of the associations of blood pressure with LVM was entirely independent of the type of indexation. CONCLUSIONS: This study showed the prominent influence of body composition on adult heart size. Indexation for LBM removed gender differences for LVM and reduced the impact of adiposity, but left the effects of blood pressure unchanged. We suggest that this approach be used for clinical and research applications.