Comparison of the Framingham Risk Score,SCORE and WHO/ISH cardiovascular risk prediction models in an Asian population

Background

Cardiovascular risk-prediction models are used in clinical practice to identify and treat high-risk populations, and to communicate risk effectively. We assessed the validity and utility of four cardiovascular risk-prediction models in an Asian population of a middle-income country.

Methods

Data from a national population-based survey of 14,863 participants aged 40 to 65 years, with a follow-up duration of 73,277 person-years was used. The Framingham Risk Score (FRS), SCORE (Systematic COronary Risk Evaluation)-high and -low cardiovascular-risk regions and the World Health Organization/International Society of Hypertension (WHO/ISH) models were assessed. The outcome of interest was 5-year cardiovascular mortality. Discrimination was assessed for all models and calibration for the SCORE models.

Results

Cardiovascular risk factors were highly prevalent; smoking 20%, obesity 32%, hypertension 55%, diabetes mellitus 18% and hypercholesterolemia 34%. The FRS and SCORE models showed good agreement in risk stratification. The FRS, SCORE-high and -low models showed good discrimination for cardiovascular mortality, areas under the ROC curve (AUC) were 0.768, 0.774 and 0.775 respectively. The WHO/ISH model showed poor discrimination, AUC = 0.613. Calibration of the SCORE-high model was graphically and statistically acceptable for men (χ² goodness-of-fit, p = 0.097). The SCORE-low model was statistically acceptable for men (χ² goodness-of-fit, p = 0.067). Both SCORE-models underestimated risk in women (p < 0.001).

Conclusions

The FRS and SCORE-high models, but not the WHO/ISH model can be used to identify high cardiovascular risk in the Malaysian population. The SCORE-high model predicts risk accurately in men but underestimated it in women.     

Value of electrocardiographic scoring systems for the assessment of thrombolytic therapy in acute myocardial infarction. The European Cooperative Study Group for Recombinant Tissue Type Plasminogen Activator

The value of the Selvester and Cardiac Infarction Injury Scores was assessed in a randomized, placebo-controlled study of intravenous recombinant tissue plasminogen activator (rt-PA) in 721 patients with acute myocardial infarction. Electrocardiograms (ECG) obtained at admission, 6 h and 10 to 22 days after the start of therapy were analysed. Patients with prior myocardial infarction or QRS duration greater than or equal to 120 ms were excluded, leaving 322 in the rt-PA group and 333 in the placebo group. Cumulative 72-h release of alpha-hydroxybutyrate dehydrogenase (HBDH) and global ejection fraction derived from angiography and nuclear scintigraphy were used as independent measures of infarct size. Predischarge results demonstrated a net benefit of rt-PA therapy, with the Selvester Score 11% lower (P less than 0.01) and the Cardiac Infarction Injury Score 5.4% lower (P = NS) in the rt-PA than the control group. Total enzyme release was reduced by 19.2% (P less than 0.001) in the rt-PA group. In patients with inferior infarction, neither enzyme release (r = 0.30 to 0.40) nor ejection fraction (r = 0.22 to 0.31) correlated well with the ECG indices of infarct size. In anterior infarction, the correlations were better, especially between the Selvester Score and enzyme release (r = 0.40 to 0.48) as well as ejection fraction (r = -0.48 to -0.67). It is concluded that ECG scoring systems, especially the Selvester Score, although imperfect are useful to assess thrombolytic therapy in clinical trials. However, their value for the management and assessment of thrombolytic therapy in individual patients is still limited.     

Cultural adaptation and validation of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) in a Mexican population

Measuring quality of life (QOL) is important, but to date, questionnaires to measure QOL in Mexican patients with osteoporosis (OP) have not been validated. A study was carried out to culturally adapt and validate the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) in a Mexican population. Interviews were performed with 160 women, 80 patients with at least one vertebral fracture, and 80 patients with OP as determined by the World Health Organization criteria. Several cultural modifications were made to the Spanish version of the QUALEFFO. Content validity was assessed by a group of experts, and a pilot study was undertaken. At the same time, the Spanish version of the Short Form 36 (Medical Outcomes Study) was applied. The mean age of patients was 71.9 ± 11.1. The QOL questionnaire showed a test–retest reproducibility (R _i = 0.94) and internal consistency (α = 0.92), while social function scored low (α = 0.46). Concurrent validity was significant (r = −0.837, p < 0.001). Significant differences were found between the two groups for pain (p < 0.05), physical function (p < 0.01), social function (p < 0.01), mental function (p < 0.05), and number of fractures (p < 0.001). Discriminatory characteristics between the groups were significant for physical (p < 0.001), social (p < 0.001), and mental (p < 0.02) function. The cultural adaptation of the QUALEFFO was consistent, homogenous, and discriminative. It also showed deterioration in the QOL group of Mexicans with vertebral fractures. The QUALEFFO can be used in a Mexican population to measure the QOL in patients with vertebral fractures after some cultural modifications to take into account local sensibilities.     

Pro B-type natriuretic peptide plasma value: A new criterion for the prediction of short- and long-term outcomes after transcatheter aortic valve implantation

Background

To determine the prognostic value of pro B-type natriuretic peptide (pro-BNP) to predict mortality after transcatheter aortic valve implantation (TAVI). Logistic EuroSCORE (LES) overestimates observed mortality after TAVI. A new risk score specific to TAVI is needed to accurately assess mortality and outcome.

Methods

Eighty-five patients were included. Indications for TAVI were nonoperable or surgically high-risk patients (LES > 20%). Pro-BNP was measured 24 h before the procedure. Cox proportional hazards model was used to evaluate clinical factors. The predictive accuracy of these Cox models was determined by using time-dependent receiver operating characteristic (ROC) curves.

Results

Pro-BNP levels (log-transformed) were significantly higher in non-survivors than in survivors at 30 days (3.36 ± 0.43 vs. 3.81 ± 0.43, p < 0.004) and at the end of follow-up (3.34 ± 0.42 vs. 3.63 ± 0.48, p < 0.011). Multivariate analysis revealed that only increased log pro-BNP levels were associated with higher mortality rate at short [hazard ratio (HR) (95% confidence intervals (CI)] = 5.35 (1.74–16.5), p = 0.003] and long-term follow-ups [HR = 11 (CI: 1.51–81.3), p = 0.018]. LES was not associated with increased mortality at either time point [HR = 1.03 (CI: 0.95–1.10), p = 0.483 and HR = 1.03 (CI: 0.98–1.07), p = 0.230, respectively]. At 30, 90, 180, and 365 days, the c-index was 0.72 for log pro-BNP and 0.63 for LES (p = 0.044).

Conclusion

Pre-procedure log transform of plasma pro-BNP levels are an independent and strong predictor of short- and long-term outcomes after TAVI and are more discriminatory than LES.     

Prospective validation of the Chinese University Prognostic Index and comparison with other staging systems for hepatocellular carcinoma in an Asian population

Background and Aim: Hepatitis B viral (HBV) infection is the predominant etiology of hepatocellular carcinoma (HCC) in Asia. Our group previously reported a staging system known as the Chinese University Prognostic Index (CUPI) for HCC populations of which HBV infection is the predominant etiology. This study aims to validate CUPI and compare with other published staging systems. Methods: We analyzed a prospective cohort of patients with newly diagnosed HCC from 2003 to 2005. All patients were staged with CUPI, Barcelona Clinic Liver Cancer Classification (BCLC), Cancer of the Liver Italian Program score (CLIP), tumor‐node‐metastasis (TNM) and Okuda systems at diagnosis. They were followed with survival data and the performance of each staging system (in terms of homogeneity, discriminatory ability and monotonicity of gradient) were analyzed and compared. Results: A total of 595 patients (80.2% with chronic HBV infection) were analyzed. The median follow‐up was 41.4 months and the median survival was 6.6 months. Multivariate analyses identified symptomatic disease, ascites, vascular involvement, Child‐Pugh‐stage, alpha‐fetoprotein and treatment to be the independent prognostic factors. CUPI could identify three groups with statistically significant survival difference (P < 0.0001). Both CUPI and CLIP had the most favorable performance in terms of discriminatory ability, homogeneity and monotonicity. CUPI performed the best in predicting 3‐month survival while CLIP performed better in predicting the outcome of 6‐ and 12‐month survival rate. BCLC was inferior to CLIP and CUPI in the overall performance. Conclusion: We have validated CUPI in a population composed of predominant HBV‐related HCC. CUPI is an appropriate staging system for HBV‐related HCC. In patients with advanced HCC, both CUPI and CLIP offer good risk stratification.     

Reliability of progressive and additive MRI scoring systems for evaluation of haemophilic arthropathy in children: Expert MRI Working Group of the International Prophylaxis Study Group

Effective treatment of haemophilic arthropathy requires a detailed evaluation of joint integrity. Methodological assessment of magnetic resonance imaging (MRI) scores are needed to assure reproducibility of measurements when comparing results of clinical trials conducted in different centres. We compared the reliability of two MRI scoring systems for assessment of haemophilic arthropathy: one progressive system that displays the most severe change and one additive system that depicts osteochondral and soft tissue-related changes. A total of 47 1.5 T MRI examinations of knees (n = 21) and ankles (n = 26) of 42 haemophilic boys, age range, 22 months to 18 years, performed at different centres (Toronto, n = 20, Europe, n = 12 and Denver, n = 15) were independently reviewed by four radiologists at two occasions. Twenty-two examinations were from children <9 years and 25 from children >/=9. Sagittal and coronal gradient-echo (MPGR, 3D FLASH with fat saturation, GRASS) images were obtained. The MRI examinations of the ankle and knee studies presented with osteochondral abnormalities in 38.5% and 23.8% of the cases respectively. The two scoring systems demonstrated an excellent inter-reader [progressive, 0.88; additive (A, e, s and h components), 0.86] and intra-reader [progressive, 0.92; additive (A, e, s and h components), 0.93] reliability using intraclass correlation coefficients (ICCs). Although ICCs were slightly higher for knees when compared with ankles, and for older children when compared with younger children, all values fell within excellent inter- and intra-reader reliability categories. The two MRI scoring systems demonstrated a comparable reliability. This result constitutes the basis for further development of a combined MRI scoring system for assessment of haemophilic arthropathy, which incorporates progressive and additive components.     

External validation and comparison of the scoring systems (S.T.O.N.E,GUY, CROES,S-ReSC) for predicting percutaneous nephrolithotomy outcomes for staghorn stones: A single center experience with 160 cases

The aim of this study was validation and comparison of stone scoring systems (S.T.O.N.E, GUY, CROES, S-ReSC) used to predict postoperative stone-free status and complications after percutaneous nephrolithotomy (PCNL) for staghorn stones. A total of 160 patients who had staghorn renal stones and underwent PCNL between January 2012 and August 2015 were included in the current retrospective study. Guy, S.T.O.N.E., S-ReSC (Seoul National University Renal Stone Complexity) and CROES (Clinical Research Office of the Endourological Society) nephrolithometry scores were calculated for each patient, and their potential association with stone-free status, operative and fluoroscopy time, and length of hospital stay (LOS) were evaluated. Postoperative complications were graded according to the modified Clavien classification, and the correlation of scoring systems with postoperative complications was also investigated. The mean CROES, S.T.O.N.E, Guy and S-ReSC scores were 143.5 ± 33.6, 9.7 ± 1.6, 3.5 ± 0.5 and 6.2 ± 2.0 respectively. The overall stone-free rate was 59%. All scoring systems were significantly correlated with stone-free status in univariate analysis. However, Guy and S-ReSC scores were the only significant independent predictor in multivariate analysis. And all four nomograms failed to predict complication rates. Current study demonstrated that Guy and S-ReSC scoring systems could effectively predict postoperative stone-free status for staghorn stones. However all four scoring systems failed to predict complication rates.     

Quantifying the impact of using Coronary Artery Calcium Score for risk categorization instead of Framingham Score or European Heart SCORE in lipid lowering algorithms in a Middle Eastern population

Background

The use of the Coronary Artery Calcium Score (CACS) for risk categorization instead of the Framingham Risk Score (FRS) or European Heart SCORE (EHS) to improve classification of individuals is well documented. However, the impact of reclassifying individuals using CACS on initiating lipid lowering therapy is not well understood. We aimed to determine the percentage of individuals not requiring lipid lowering therapy as per the FRS and EHS models but are found to require it using CACS and vice versa; and to determine the level of agreement between CACS, FRS and EHS based models.

Methods

Data was collected for 500 consecutive patients who had already undergone CACS. However, only 242 patients met the inclusion criteria and were included in the analysis. Risk stratification comparisons were conducted according to CACS, FRS, and EHS, and the agreement (Kappa) between them was calculated.

Results

In accordance with the models, 79.7% to 81.5% of high-risk individuals were down-classified by CACS, while 6.8% to 7.6% of individuals at intermediate risk were up-classified to high risk by CACS, with slight to moderate agreement. Moreover, CACS recommended treatment to 5.7% and 5.8% of subjects untreated according to European and Canadian guidelines, respectively; whereas 75.2% to 81.2% of those treated in line with the guidelines would not be treated based on CACS.

Conclusion

In this simulation, using CACS for risk categorization warrants lipid lowering treatment for 5–6% and spares 70–80% from treatment in accordance with the guidelines. Current strong evidence from double randomized clinical trials is in support of guideline recommendations. Our results call for a prospective trial to explore the benefits/risks of a CACS-based approach before any recommendations can be made.     

Validation of the revised international prognostic scoring system (IPSS‐R) in patients with lower‐risk myelodysplastic syndromes: a report from the prospective European LeukaemiaNet MDS (EUMDS) registry

Baseline characteristics, disease‐management and outcome of 1000 lower‐risk myelodysplastic syndrome (MDS) patients within the European LeukaemiaNet MDS (EUMDS) Registry are described in conjunction with the validation of the revised International Prognostic Scoring System (IPSS‐R). The EUMDS registry confirmed established prognostic factors, such as age, gender and World Health Organization 2001 classification. Low quality of life (EQ‐5D visual analogue scale score) was significantly associated with reduced survival. A high co‐morbidity index predicted poor outcome in univariate analyses. The IPSS‐R identified a large group of 247 patients with Low (43%) and Very low (23%) risk score within the IPSS intermediate‐1 patients. The IPSS‐R also identified 32 High or Very high risk patients within the IPSS intermediate‐1 patients. IPSS‐R was superior to the IPSS for predicting both disease progression and survival. Seventy percent of patients received MDS‐specific treatment or supportive care, including red blood cell transfusions (51%), haematopoietic growth factors (58%) and iron chelation therapy (8%), within 2 years of diagnosis; while 30% of the patients only required active monitoring. The IPSS‐R proved its utility as a more refined risk stratification tool for the identification of patients with a very good or poor prognosis and in this lower‐risk MDS population.     

Cardiovascular risk prediction in the general population with use of suPAR,CRP, and Framingham Risk Score

Background

The inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR) and C-reactive protein (CRP) independently predict cardiovascular disease (CVD). The prognostic implications of suPAR and CRP combined with Framingham Risk Score (FRS) have not been determined.

Methods

From 1993 to 1994, baseline levels of suPAR and CRP were obtained from 2315 generally healthy Danish individuals (mean [SD] age: 53.9 [10.6] years) who were followed for the composite outcome of ischemic heart disease, stroke and CVD mortality.

Results

During a median follow-up of 12.7 years, 302 events were recorded. After adjusting for FRS, women with suPAR levels in the highest tertile had a 1.74-fold (95% confidence interval [CI]: 1.08–2.81, p = 0.027) and men a 2.09-fold (95% CI: 1.37–3.18, p < 0.001) increase in risk compared to the lowest tertile. Including suPAR and CRP together resulted in stronger risk prediction with a 3.30-fold (95% CI: 1.36–7.99, p < 0.01) increase for women and a 3.53-fold (1.78–7.02, p < 0.001) increase for men when both biomarkers were in the highest compared to the lowest tertile. The combined extreme tertiles of suPAR and CRP reallocated individuals predicted to an intermediate 10-year risk of CVD of 10–20% based on FRS, to low (< 10%) or high (> 20%) risk categories, respectively. This was reflected in a significant improvement of C statistics for men (p = 0.034) and borderline significant for women (p = 0.054), while the integrated discrimination improvement was highly significant (P ≤ 0.001) for both genders.

Conclusions

suPAR provides prognostic information of CVD risk beyond FRS and improves risk prediction substantially when combined with CRP in this setting.     

Prevalence and risk factors for diabetic neuropathy in an urban south Indian population: the Chennai Urban Rural Epidemiology Study (CURES-55)

Aims This study was conducted to determine the prevalence of, and risk factors for, diabetic neuropathy (DN) in south Indian Type 2 diabetic subjects. Methods Subjects were recruited from the Chennai Urban Rural Epidemiology Study, conducted on a representative cohort from Chennai city. A total of 1629 diabetic subjects were included, of whom 1291 were known to have diabetes (KD) subjects and 338 were randomly selected newly detected diabetic (NDD) subjects. Neuropathy was diagnosed if vibratory perception threshold at the great toe, measured by biothesiometry, exceeded mean + 2 sd of a healthy non-diabetic study population aged 20–45 years (cut point ≥ 20 V). Results The overall prevalence of DN was 26.1% (age-adjusted 13.1%) with no significant difference in gender. The prevalence of neuropathy was significantly higher in KD subjects compared with NDD subjects (27.8 vs. 19.5%, P = 0.002). The prevalence of diabetic retinopathy (24.1 vs. 15.3%, P < 0.0001) and hypertension (51.1 vs. 40.0%, P < 0.0001) were higher in those with neuropathy compared with those without. The odds ratio for neuropathy in subjects with duration of diabetes > 15 years compared with ≤ 5 years was 5.7 (95% confidence interval: 3.52–9.08, P < 0.0001). Regression analysis showed age (P < 0.0001), glycated haemoglobin (P = 0.001) and duration of diabetes (P = 0.045) to be significantly associated with neuropathy. Conclusions This cross-sectional population-based study shows that, among urban south Indian Type 2 diabetic subjects, the prevalence of DN is 26.1% and that DN is significantly associated with age, glycated haemoglobin and duration of diabetes.     

学龄期流动人口血防教育策略和模式的探讨

目的探索学龄期流动人口血防教育的策略和模式。方法随机抽取3所外来民工子弟学校,对5年级以上学生整群抽样,进行血防教育,对血防教育前后学生的防治知识、相关行为和教育需求等作统计分析,评价干预效果。结果奉贤区学龄期流动人口83.68%来自血吸虫病流行区,干预后学生的血防知识水平、行为正确性、教育需求和知识分享水平分别提高了99.64%、63.68%、11.99%和16.78%。结论开展血防教育活动能提高学龄期流动人口的血防能力和分享水平,而系统化、规范化学校血防教育制度,适合学龄期流动人口学习特点的血防教育模式能使学校-家庭-社会的连锁宣传效应事半功倍。     

Comparative assessment of the HAS-BLED score with other published bleeding risk scoring schemes,for intracranial haemorrhage risk in a non-atrial fibrillation population: The Chin-Shan Community Cohort Study

Background

The HAS-BLED score is a validated bleeding risk model for predicting major bleeding events in anticoagulated individuals with atrial fibrillation (AF). It remains uncertain whether the HAS-BLED score could identify non-AF individuals at risk of developing intracranial haemorrhage (ICH), which is the most intractable and devastating major bleeding complication.

Methods

We assessed the predictive value of a modified HAS-BLED and other bleeding risk scoring models to predict the risk for ICH in the Chin-Shan Community Cohort, which followed 1899 women and 1703 men, aged > 35 years, for a median of 15.9 years. ICH events (including haemorrhagic strokes) were ascertained according to questionnaires and the national register database.

Results

Of 3524 individuals without baseline AF, 54 ICH events occurred during follow-up. The risk for ICH was raised with increasing HAS-BLED scores, and was significantly associated with uncontrolled hypertension and older age (Odds Ratios [95% confidence interval (CI)], 4.2[2.3–7.6] and 1.9[1.1–3.4], respectively). Among the five bleeding risk scoring schemes tested, HAS-BLED had highest general discrimination performance (c-statistic [95% CI], 0.72 [0.67–0.78]), and better ability to discriminate between those who were at risk for ICH and who were not (NRI, net reclassification improvement, all p < 0.05, compared to other four scoring schemes).

Conclusion

The HAS-BLED score had the highest general discrimination performance and best ability to discriminate risk for ICH. This score may be of clinical use in predicting the risk for occurrence of ICH among non-AF individuals.     

Genetic variants of chromosome 9p21.3 region associated with coronary artery disease and premature coronary artery disease in an Asian Indian population

IntroductionAsian Indians have a propensity for premature, severe, and diffuse coronary artery disease (CAD). Several single-nucleotide polymorphisms (SNPs) in the ‘core CAD’ region of the chromosomal region 9p21.3 are known to be strongly associated with CAD.ObjectivesWe aimed to study SNPs in the 9p21.3 region associated with CAD and premature CAD and identify their association with demographic and clinical characteristics in an Asian Indian population.MethodsSNP genotyping was performed for 30 SNPs of the 9p21.3 region using MassARRAY^® technology. Along with demographic and SNP data analysis, we also performed multivariate logistic regression analysis and multifactor dimensionality reduction analysis to study SNP–SNP and SNP–demographic/clinical variable interactions.ResultsOur results suggest that females are at a higher risk of premature CAD. We found that SNPs rs1333045 (CC), rs16905599 (AA), rs2383206 (GG), rs2383208 (AG), and rs4977574 (GG) were significantly associated with premature CAD. When adjusted for covariates/confounders, we found that rs2383206 showed the strongest risk association with CAD followed by rs16905599 and rs2383208. Further, SNPs rs1333049 (CC) and rs4977574 (GG) were found to be exclusively associated with premature CAD cases, suggesting their potential as genetic markers for premature CAD in the local population. Upon gender-based stratification, it was found that rs10757272 (TT and TC) is significantly associated with eightfold to ninefold CAD risk specifically among females. SNP rs7865618 (GG) is significantly associated with more than 2.5-fold CAD risk specifically among males.ConclusionOur study suggests that SNPs at the 9p21 risk locus may be used to generate a reliable genetic risk score along with markers at other loci.     

Axillary approach for transcatheter aortic valve implantation: optimization of the endovascular treatment for the aortic valve stenosis

Introduction and objectives

To validate the axillary approach as a safe and efficient option for the transcatheter aortic valve implantation in patients who have contraindication for femoral approach at three Spanish hospitals.

Methods

We included patients with severe symptomatic aortic stenosis at very high or prohibitive surgical risk, selected by a multidisciplinary team, for transcatheter aortic valve implantation, and had contraindication to the femoral approach.

Results

We included 19 of 186 (10.5%) patients, who were implanted a percutaneous aortic valve, between November 2008 and March 2010. The mean age was 78.3 (standard deviation [SD] ± 8.65) years and 73.7% were males. The mean logistic EuroSCORE was 28.7% (SD ± 16.3%). The procedural success rate was 100%. After the procedure the maximum transvalve gradient decreased from 81.7 mmHg (SD ± 21.5) to 15.8 mmHg (SD ± 5.5), and no patient presented residual aortic regurgitation >2. The all-cause mortality, with a mean follow-up time of 9.2 (SD ± 3.2) months was 10.5%, and the in-hospital and 30-day mortality rates were 0%. The global incidence of major complications due to the procedure was 15.7%. Definitive pacemaker implantation was carried out for atrioventricular block in 8 patients (44.4%).

Conclusions

The axillary approach for transcatheter aortic valve implantation using the CoreValve^® and contraindication to the femoral approach is safe and efficient for selected patients, with excellent results in terms of success implantation and in hospital and 30-day mortality.Full English text available from: www.revespcardiol.org     

Genetic screening for individuals at high risk for type 1 diabetes in the general population using HLA Class II alleles as disease markers. A comparison between three European populations with variable rates of disease incidence

BACKGROUND: To develop screening strategies for identification of individuals at increased genetic risk for type 1 diabetes in three populations with variable disease incidence rates and distinct ethnic origin. METHODS: A stepwise HLA DQB1-DQA1-DRB1-based screening approach was evaluated. Patients with childhood-onset type 1 diabetes were recruited from Finland (n = 1739), Hungary (n = 149), and Greece (n = 119). Consecutive newborns (2568 from Finland and 1047 from Greece) or healthy schoolchildren (n = 177 from Hungary) served as controls. RESULTS: The DQB1*02/0302 genotype conferred the highest disease risk in all populations. The DQB1*02/y (y not equal DQB1*0301,*0302,*0602,*0603, *0604) genotypes were more common and conferred a higher disease risk in the Greek population (OR 4.9) compared to the Finns (OR 1.2). DQB1*0302/x (x not equal DQB1*02, *0301, *0602, *0603, *0604) genotypes were, in contrast, more prevalent among Finnish cases (32.7%) as compared to Hungarians (18.1%) or Greeks (13.5%). The protective DQB1*0602 or *0603 positive genotypes were most common in the Finns, while DQB1*0301 was more common in Hungarians and Greeks. In all groups, DQA1 and DRB1*04 typing considerably increased the sensitivity of the DQB1-based screening. The different high-risk genotype combinations present in about 10% of the background population had a diagnostic sensitivity of 60% in Finland and 80% in Hungary and Greece. CONCLUSIONS: HLA DR-DQ-based screening is a feasible tool for the identification of individuals at increased genetic risk for type 1 diabetes in populations with diverse genetic background. The risk markers should, however, be individually selected for the target population since the screening efficiency of various markers is highly dependent on the ethnic group studied.