SNP and Structural Study of the Notch Superfamily Provides Insights and Novel Pharmacological Targets against the CADASIL Syndrome and Neurodegenerative Diseases.

The evolutionary conserved Notch signaling pathway functions as a mediator of direct cell-cell communication between neighboring cells during development. Notch plays a crucial role in various fundamental biological processes in a wide range of tissues. Accordingly, the aberrant signaling of this pathway underlies multiple genetic pathologies such as developmental syndromes, congenital disorders, neurodegenerative diseases, and cancer. Over the last two decades, significant data have shown that the Notch signaling pathway displays a significant function in the mature brains of vertebrates and invertebrates beyond neuronal development and specification during embryonic development. Neuronal connection, synaptic plasticity, learning, and memory appear to be regulated by this pathway. Specific mutations in human Notch family proteins have been linked to several neurodegenerative diseases including Alzheimer's disease, CADASIL, and ischemic injury. Neurodegenerative diseases are incurable disorders of the central nervous system that cause the progressive degeneration and/or death of brain nerve cells, affecting both mental function and movement (ataxia). There is currently a lot of study being conducted to better understand the molecular mechanisms by which Notch plays an essential role in the mature brain. In this study, an in silico analysis of polymorphisms and mutations in human Notch family members that lead to neurodegenerative diseases was performed in order to investigate the correlations among Notch family proteins and neurodegenerative diseases. Particular emphasis was placed on the study of mutations in the Notch3 protein and the structure analysis of the mutant Notch3 protein that leads to the manifestation of the CADASIL syndrome in order to spot possible conserved mutations and interpret the effect of these mutations in the Notch3 protein structure. Conserved mutations of cysteine residues may be candidate pharmacological targets for the potential therapy of CADASIL syndrome.

CD44 Expression in Clear Cell Renal Cell Carcinoma (ccRCC) Correlates with Tumor Grade and Patient Survival and Is Affected by Gene Methylation.

Clear cell RCC (ccRCC) represents the most common type of kidney cancer, with surgery being the only potential curative treatment. Almost one-third of ccRCC patients relapse either locally or as cases of distant metastases. Several biomarkers have been employed in order to separate ccRCC patients with better prognosis or to predict treatment outcomes, with limited results. CD44 is a membrane glycoprotein with multiple roles in normal development but also cancer. Recently, the CD44 standard isoform has been implicated in tumor progression and the metastasis cascade through microenvironment interactions. Here, through CD44 immunohistochemical staining of ccRCC patient samples and TCGA data analysis, we sought to elucidate the expression patterns (mRNA and protein) of CD44 in clear cell RCC and correlate its expression with clinicopathological parameters. We were able to show that CD44 expression presents a positive association with tumor grade and overall survival, predicting a worse patient outcome in ccRCC. In addition, our data indicate that the CD44 mRNA upregulation can be attributed to reduced gene methylation, implicating epigenetic gene regulation in ccRCC development and progression.

Seroprevalence of Toxoplasma gondii among HIV Positive Patients under Surveillance in Greek Infectious Disease Units: A Screening Study with Comparative Evaluation of Serological Methods.

This study aims to screen for IgG antibodies against Toxoplasma gondii (T. gondii) in the sera of 155 newly diagnosed Human Immunodeficiency Virus (HIV) positive patients under surveillance in Greek Infectious Disease Units. Additionally, risk factors based on patient demographics were examined, and a comparative evaluation of commercially available serological methods was conducted. Three methods were employed to detect IgG antibodies against T. gondii: Enzyme-Linked Immunosorbent Assay (ELISA), Indirect Immunofluorescence Antibody Test (IFAT), and Western Blot (WB), which was used as a reference here. Forty-nine sera samples were true-positive for IgG antibodies against T. gondii, resulting in a 31.61% positivity rate, and the immunoassay test statistical reliability analysis resulted in higher IFAT accuracy (90.97%) compared to ELISA (76.26%). Furthermore, statistical analysis of demographic and immunological data included in the study placed female and foreign/non-Greek individuals at 2.24 (p = 0.0009) and 2.34 (p = 0.0006) times higher risk of positive T. gondii IgG testing compared to their male and Greek counterparts, respectively. Our findings on positivity rates and comparative serology underscore the importance of early and suitable screening measures for newly diagnosed HIV+ patients to mitigate the life-threatening outcomes that may arise from a potential subsequent T. gondii activation.

Comparison Between EPI DWI and PROPELLER DWI in Brain MR Imaging.

OBJECTIVE: EPI DWI is a routinely used sequence in brain imaging but it has limitations when it comes to SNR and artifact reduction. PROPELLER DWI has the benefit of improving image quality compared to EPI DWI. The aim of this study is to compare the EPI DWI sequence in brain MR imaging with the PROPELLER DWI sequence. The objective is to identify which sequence is more beneficial in brain imaging by evaluating image quality and the depiction of pathologies. MATERIALS AND METHODS: A total of 101 patients (55 females and 46 males, mean age 56 years) underwent brain MRI examination on a 1.5 T scanner. EPI DWI and PROPELLER DWI sequences were acquired in every exam and were reviewed by 2 radiologists. The images were evaluated by performing a quantitative analysis based on Relative Contrast and a qualitative analysis (overall image quality, conspicuousness of lesions, artifact reduction, etc.). RESULTS: In both the qualitative and quantitative analysis PROPELLER DWI achieved better results than EPI DWI. PROPELLER DWI showed statistical significance in the overall image quality (P < 0.001), the elimination of susceptibility (P < 0.001) and flow pulsation artifacts (P < 0.001), as well as in the contrast between CSF with white (P < 0.001) and grey matter (P < 0.001). Also, PROPELLER DWI presented better delineation of pathologies like ischemic strokes, metastasis, tumors and vasogenic edemas than conventional EPI DWI. CONCLUSION: PROPELLER DWI was the preferred sequence during the image evaluation. Compared to EPI DWI, PROPELLER DWI managed to reduce susceptibility and flow pulsation whilst achieving higher image quality and lesion delineation and earlier depiction of ischemic strokes than the conventional EPI DWI. PROPELLER DWI may be incorporated in brain MR imaging replacing EPI DWI.

Viral Infections and Schizophrenia: A Comprehensive Review.

Schizophrenia is a complex mental disorder with multiple genetic and environmental factors contributing to its pathogenesis. Viral infections have been suggested to be one of the environmental factors associated with the development of this disorder. We comprehensively review all relevant published literature focusing on the relationship between schizophrenia and various viral infections, such as influenza virus, herpes virus 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), retrovirus, coronavirus, and Borna virus. These viruses may interfere with the normal maturation of the brain directly or through immune-induced mediators, such as cytokines, leading to the onset of schizophrenia. Changes in the expression of critical genes and elevated levels of inflammatory cytokines have been linked to virally-induced infections and relevant immune activities in schizophrenia. Future research is necessary to understand this relationship better and provide insight into the molecular mechanisms underlying the pathophysiology of schizophrenia.

Nine Months of Hybrid Intradialytic Exercise Training Improves Ejection Fraction and Cardiac Autonomic Nervous System Activity.

Cardiovascular disease is the most common cause of death in hemodialysis (HD) patients. Intradialytic aerobic exercise training has a beneficial effect on cardiovascular system function and reduces mortality in HD patients. However, the impact of other forms of exercise on the cardiovascular system, such as hybrid exercise, is not clear. Briefly, hybrid exercise combines aerobic and strength training in the same session. The present study examined whether hybrid intradialytic exercise has long-term benefits on left ventricular function and structure and the autonomous nervous system in HD patients. In this single-group design, efficacy-based intervention, twelve stable HD patients (10M/2F, 56 ± 19 years) participated in a nine-month-long hybrid intradialytic training program. Both echocardiographic assessments of left ventricular function and structure and heart rate variability (HRV) were assessed pre, during and after the end of the HD session at baseline and after the nine-month intervention. Ejection Fraction (EF), both assessed before and at the end of the HD session, appeared to be significantly improved after the intervention period compared to the baseline values (48.7 ± 11.1 vs. 58.8 ± 6.5, p = 0.046 and 50.0 ± 13.4 vs. 56.1 ± 3.4, p = 0.054 respectively). Regarding HRV assessment, hybrid exercise training increased LF and decreased HF (p < 0.05). Both conventional Doppler and tissue Doppler imaging indices of diastolic function did not change after the intervention period (p > 0.05). In conclusion, long-term intradialytic hybrid exercise training was an effective non-pharmacological approach to improving EF and the cardiac autonomous nervous system in HD patients. Such exercise training programs could be incorporated into HD units to improve the patients' cardiovascular health.

Association of endometriosis with cardiovascular disease: Genetic aspects (Review).

Cardiovascular disease (CVD) comprises a broad spectrum of pathological conditions that affect the heart or blood vessels, including sequelae that arise from damaged vasculature in other organs of the body, such as the brain, kidneys or eyes. Atherosclerosis is a chronic inflammatory disease of the arterial intima and is the primary cause of coronary artery disease, peripheral vascular disease, heart attack, stroke and renal pathology. It represents a leading cause of mortality worldwide and the loss of human productivity that is marked by an altered immune response. Endometriosis is a heritable, heterogeneous, common gynecological condition influenced by multiple genetic, epigenetic and environmental factors, affecting up to 10% of the female population of childbearing age, causing pain and infertility; it is characterized by the ectopic growth of endometrial tissue outside the uterine cavity. Of note, epidemiological data obtained thus far have suggested a link between endometriosis and the risk of developing CVD. The similarities observed in specific molecular and cellular pathways of endometriosis and CVD may be partially explained by a shared genetic background. The present review presents and discusses the shared genetic factors which have been reported to be associated with the development of both disorders.

Analysis of RANK-c interaction partners identifies TRAF3 as a critical regulator of breast cancer aggressiveness.

Breast cancer is a highly heterogeneous disease both at the histological and molecular levels. We have previously shown that RANK-c is a regulator of NF-κB signaling and exerts a suppressive effect on aggressive properties of ER negative breast cancer cells, while there is an opposite effect on ER positive cell lines. In order to identify molecular determinants that govern the opposing function of RANK-c in breast cancer cells we employed the two cell lines with the highest degree of phenotypic divergence upon RANK-c-expression (SKBR3 and BT474) and identified proteins that interact with RANK-c by affinity-enrichment mass spectrometry (AE-MS) analysis. Annotating enriched proteins with NF-κB signaling pathway revealed TRAF3 as an interacting partner of RANK-c in SKBR3 cell protein lysates, but not in BT474 breast cancer cells in which RANK-c induces cell aggressiveness. To determine the role of TRAF3 in the phenotype of BT474-RANK-c cells, we reconstructed the TRAF3/RANK-c interaction both in parental BT474 and RANK-c expressing cells and tested for aggressive properties through colony formation, migration and invasion assays. TRAF3 forced expression was able to reverse BT474 phenotypic changes imposed by RANK-c, rendering cells less aggressive. Finally, TRAF3 gene expression data and TRAF3 immunohistochemical (IHC) analysis on breast cancer samples indicated that TRAF3 expression correlates with Overall Survival (OS), Recurrence Free Survival (RFS) and several clinicopathological parameters (histological grade, proliferation index) of breast cancer disease.

Anthropometric, Lifestyle Characteristics, Adherence to the Mediterranean Diet, and COVID-19 Have a High Impact on the Greek Adolescents' Health-Related Quality of Life.

OBJECTIVE: The study aimed at analyzing the relationship between anthropometric characteristics, lifestyle, and dietary habits, as well as the burden of the pandemic on the health-related quality of life among Greek pupils. RESEARCH METHODS AND PROCEDURES: On the whole, 2088 adolescents aged 12-18 years from Attica, Greece, were enlisted in this school-based cross-sectional study that took place in May-December 2021. Health-related quality of life was estimated through the KIDSCREEN-27 questionnaire, adherence to the Mediterranean diet-through the KIDMED test. For the empirical and econometric analyses, the Mann-Whitney U and Kruskal-Wallis means comparison tests were utilized; multiple linear regression was used accordingly. RESULTS: The present study provides evidence to the fact that boys, younger adolescents, adolescents living with both parents and with highly educated mothers had a better health-related quality of life. Concerning their eating practices, positive predictors were consuming a better-quality breakfast, having all five meals daily, consuming lunch and dinner with parents, and higher adherence to the Mediterranean diet. Moreover, sufficient night sleep time, fewer hours spent on screen viewing, more frequent walks, and having hobbies were linked to the health-related quality of life with a positive sign. In contrast, negative predictors were higher body mass index and everyday life difficulties due to the COVID-19 pandemic crisis. CONCLUSIONS: Greek adolescents' anthropometric characteristics, BMI, lifestyle and sedentary habits, eating habits, and adherence to the Mediterranean diet were significantly related to their perceived health-related quality of life during the pandemic.

Cellular Senescence in Normal Mammary Gland and Breast Cancer. Implications for Cancer Therapy.

Cellular senescence (CS) is a major homeostatic biological process, which plays a key role in normal tissue development and provides protection from stressful cell insults. The role of CS in mammary-gland development and breast cancer is not well understood. While there is a lack of experimental data on the role of CS in the development of the pre-pubertal mammary gland, there is evidence for a biphasic senescence response in adult normal-mammary-epithelial cells, where the bypass of the first senescence barrier (M0) seems to be a key step in the development of premalignant lesions, with genetic abnormalities that resemble in situ breast carcinoma. Further, there is accumulating evidence for the role of cellular senescence in breast-cancer response, regarding treatment and patient outcome. Here, we review the current literature on cellular senescence, in epithelial-mammary cells, breast-cancer cells, and breast-tumor-microenvironment-resident cells. Furthermore, we discuss its putative role in breast-cancer response, regarding treatment and disease progression. In addition, we provide preliminary evidence of CS in breast-cancer-microenvironment cells, such as tumor-associated fibroblasts and tumor-infiltrating lymphocytes, by employing the novel GL13 lipofuscin stain, as a marker of cellular senescence.

CYP1A2 polymorphisms modify the association of habitual coffee consumption with appetite, macronutrient intake, and body mass index: results from an observational cohort and a cross-over randomized study.

BACKGROUND/OBJECTIVES: Evidence regarding the influence of coffee on appetite and weight control is equivocal and the influence of covariates, such as genetic variation in caffeine metabolism, remains unknown. Herein, we addressed the novel hypothesis that genetic variation in CYP1A2, a gene responsible for more than 95% of caffeine metabolism, differentially impacts the association of coffee consumption with appetite and BMI among individuals with different genetic predispositions to obesity. SUBJECTS/METHODS: A cross-over randomized intervention study involving 18 volunteers assessed the effects of coffee consumption on dietary intake, appetite, and levels of the appetite-controlling hormones asprosin and leptin. Data on habitual coffee intake, BMI, and perceived appetite were obtained from an observational cohort of 284 volunteers using validated questionnaires. Participants were stratified according to a validated genetic risk score (GRS) for obesity and to the -163C > A (rs762551) polymorphism of CYP1A2 as rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers. RESULTS: Coffee consumption led to lower energy and dietary fat intake and circulating asprosin levels (P for interaction of rs762551 genotype*coffee consumption=0.056, 0.039, and 0.043, respectively) as compared to slow/intermediate metabolizers. High coffee consumption was more prevalent in rapid compared to slow metabolizers (P = 0.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption = 0.002 and 0.048, respectively). This differential association of rs762551 genotype and coffee consumption with BMI was more evident in individuals at higher genetic risk of obesity (mean adjusted difference in BMI = -5.82 kg/m2 for rapid versus slow/intermediate metabolizers who consumed more than 14 cups of coffee per week). CONCLUSIONS: CYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. This association is more evident in subjects with high genetic predisposition to obesity. ClinicalTrials.gov: registered Clinical Trial NCT04514588.

The Importance of Use of the On-line Databases as a Source for Systematic Review of Toxoplasmosis Screening During Pregnancy.

BACKGROUND: Infection with the parasite Toxoplasma gondii is a common infection in animals and humans worldwide. This infection can occur after ingestion of water or food contaminated with cat oocytes, ingestion of tissue cysts in mammalian and avian meat and congenitally. The prenatal infection can lead to Congenital Toxoplasmosis with miscarriage or stillbirth. After infection, laboratory tests are positive within 2-3 weeks and remain positive throughout life. However, testing for Toxoplasma infection during pregnancy is necessary in some countries, while in others it is not a mandatory "screening" test. OBJECTIVE: The aim of this study was to review systematically the screening of toxoplasmosis in pregnancy in different countries worldwide. METHODS: Cohorts, retrospective and cross-sectional studies were incorporated in our review, finally including 11 articles from an initial pool of 1532 related papers. RESULTS: The seroprevalence of pregnant women varies from countries with low prevalence to regions with high prevalence and screening policies also differ. Most countries worldwide have control policies, while Germany and Mexico that do not have systematic screening for Toxoplasma during the prenatal period. CONCLUSION: Our results show that Congenital Toxoplasmosis is very rare in some countries and it is very difficult to find a balance between potential risk and benefit of a screening program. For this reason, some countries are limited to prenatal counseling to reduce CT. In addition, the reduction of major sources of contamination especially in developing countries is the most important prevention measure.

RANK-C Expression Sensitizes ER-Negative, EGFR-Positive Breast Cancer Cells to EGFR-Tyrosine Kinase Inhibitors (TKIs).

BACKGROUND: We have previously shown that overexpression of RANK-c in ER-negative breast cancer cell lines attenuates aggressive properties of cancer cells, partially through a RANK-c/EGFR interaction. EGFR inhibition through TKIs in breast cancer has been tested in triple-negative disease settings with limited clinical benefit for patients. Here we test if expression of RANK-c in ER-negative breast cancer cells in conjunction with treatment with TK inhibitors (erlotinib or gefitinib) can affect survival and colony-forming capacity of cancer cells. METHODS: Stably expressing MDA-MB-231-RANK-c and SKBR3-RANK-c cells were employed to test proliferation and colony formation in the presence of TKIs. In addition, Western blot analysis was performed to dissect EGFR related signaling cascades upon TK inhibition in the presence of RANK-c. RESULTS: Interestingly the two RANK-c expressing, ER-negative cells lines presented with a distinct phenotype concerning TKI sensitivity upon treatment. MDA-MB-231-RANK-c cells had a higher sensitivity upon gefitinib treatment, while erlotinib decreased the proliferation rate of SKBR3-RANK-c cells. Further, colony formation assays for MDA-MB-231-RANK-c cells showed a decrease in the number and size of colonies developed in the presence of erlotinib. In addition, RANK-c seems to alter signaling through EGFR after TKI treatment in a cell type-specific manner. CONCLUSIONS: Our results indicate that ER-negative breast cancer cells that express RANK-c alter their sensitivity profile against tyrosine kinase inhibitors (erlotinib and gefitinib) in a cell type-specific and culture substrate-dependent manner.

Awareness, Knowledge and Risky Behaviors of Sexually Transmitted Diseases among Young People in Greece.

Sexually transmitted diseases (STDs) affect mainly young individuals and cause health, social, and economic problems worldwide. The present study used a web questionnaire to assess the awareness, knowledge, sexual behaviors, and common practices regarding STDs in young Greek adults. The 1833 individuals, aged 18-30 years, who responded to the study seem to be particularly knowledgeable regarding STDs such as AIDS (97.7%), warts (97%), Chlamydia (92.2%), genital herpes (89.9%), syphilis (81.9%), and gonorrhea (72.1%), whereas lower percentages were noted for trichomoniasis (39.3%), Molluscum contagiosum (12.9%), mycoplasmosis (11.6%), and amoebiasis (7.4%). Regarding oral STD transmission, participants replied correctly for genital herpes (45%), warts (35.8%), and AIDS (HIV; 33.8%), whereas 30.2% were unfamiliar with oral sexual transmission. Of the participants, 52% were not aware that STDs might cause infertility. Only 40.4% of the respondents reported always using condoms during sexual intercourse, and 48.6% had never been tested for STDs. The majority of the young population (55%) presented a moderate knowledge STD score (41-60%) and was associated with demographic parameters such as age, gender, sexual preference, number of sexual partners, and residence (p < 0.05). These findings provide important information regarding the prevention of STDs and highlight the significance of developing more effective sex education programs for young people in Greece.

Animal Coronaviruses Induced Apoptosis.

Apoptosis is a form of programmed death that has also been observed in cells infected by several viruses. It is considered one of the most critical innate immune mechanisms that limits pathogen proliferation and propagation before the initiation of the adaptive immune response. Recent studies investigating the cellular responses to SARS-CoV and SARS-CoV-2 infection have revealed that coronaviruses can alter cellular homeostasis and promote cell death, providing evidence that the modulation of apoptotic pathways is important for viral replication and propagation. Despite the genetic diversity among different coronavirus clades and the infection of different cell types and several hosts, research studies in animal coronaviruses indicate that apoptosis in host cells is induced by common molecular mechanisms and apoptotic pathways. We summarize and critically review current knowledge on the molecular aspects of cell-death regulation during animal coronaviruses infection and the viral-host interactions to this process. Future research is expected to lead to a better understanding of the regulation of cell death during coronavirus infection. Moreover, investigating the role of viral proteins in this process will help us to identify novel antiviral targets related to apoptotic signaling pathways.

The "Virtual Digital Twins" Concept in Precision Nutrition.

Nutritional and lifestyle changes remain at the core of healthy aging and disease prevention. Accumulating evidence underscores the impact of genetic, metabolic, and host gut microbial factors on individual responses to nutrients, paving the way for the stratification of nutritional guidelines. However, technological advances that incorporate biological, nutritional, lifestyle, and health data at an unprecedented scale and depth conceptualize a future where preventative dietary interventions will exceed stratification and will be highly individualized. We herein discuss how genetic information combined with longitudinal metabolomic, immune, behavioral, and gut microbial parameters, and bioclinical variables could define a digital replica of oneself, a "virtual digital twin," which could serve to guide nutrition in a personalized manner. Such a model may revolutionize the management of obesity and its comorbidities, and provide a pillar for healthy aging.

Site-specific use of molecular markers could be a promising prognostic tool in colorectal cancer.

Proximal and distal colorectal carcinomas (CRCs) are generally considered as genetically and clinicopathologically distinct disease entities. Tumor location has been proposed as an additional prognostic indicator and -more recently- as a factor with significant influence on the prognostic value of particular molecular markers and/or combination of markers (KRAS, MSI, APC/MSI), allowing the discrimination of specific disease subsets with considerably disparate outcome and the identification of high risk cases. This article examines the clinical importance of particular recent proposals on this specific issue. Their strengths and limitations, as well as issues requiring further elucidation and practical problems hampering their clinical implementation are briefly discussed. Moreover, some suggestions intending to improve research methodology on this specific theme and to render the clinical use of this novel approach more effective and feasible, are presented. Hopefully, the assessment of certain molecular markers in a site-specific fashion could be another step towards personalized management of CRC, improving and complementing the molecular classification of the disease.

Genetics in the Clinical Decision of Antiplatelet Treatment.

BACKGROUND: Coronary artery disease remains the leading cause of death globally. Dual antiplatelet treatment with aspirin and aP2Y12 receptor significantly reduces thrombotic events. However, antiplatelet drug response displays considerable interindividual variability. METHODS: Genetic factors account for up to 70% of impaired drug response. A number of genes encoding proteins involved in the pharmacokinetic pathway have been found to alter drug response. RESULTS: According to most studies, CYP2C19 gene is the strongest genetic determinant. The novel antiplatelet agents prasugrel and ticagrelor, seem to overcome genetic restrictions but in expense of increased bleeding rates. Achieving a balance between adequate platelet inhibition and bleeding complications is challenging. CONCLUSION: Genetic screening may provide valuable guidance towards an efficient antiplatelet treatment. However, the lack of randomized controls trials testing the effect of a genotype-guided therapy, forbids the implementation of genetic testing into clinical practice.

Incidence and risk factors of coronary heart disease in elderly patients on chronic hemodialysis.

AIM: To determine the incidence of coronary heart disease (CHD) in patients (pts) over 65 years (y) and its relation to common risk factors. METHODS: We retrospectively studied 128 hemodialysis (HD) pts (80 M and 48 F), mean age 73+/-6.5 years, mean time on HD 44.4+/-26.4 months and BMI 25.4+/-3 kg/m2. They were evaluated for: age, sex, smoking, diabetes, hypertension, left ventricular hypertrophy, secondary hyperparathyroidism (SHP), inflammation, as evidence by elevated level of hsCRP, hyperhomocysteinemia (HOC), time on HD, fluid overload and adequacy of HD. Forty-eight pts (37%) had CAD diagnosed by coronary angiography in 22 (46%) and (201)TL-chloride dipyridamole stress test in 26 (54%). RESULTS: There was a statistically significant correlation between CAD and increasing age (p<0.0001). The relative risk was significantly increased concerning: (1) male over female pts (RR: 1.95, p<0.01), (2) diabetic vs. non diabetic pts (RR: 2.09, p<0.001), (3) patients with SHP over pts with iPTH values<250 pg/ml (RR: 2.16, p<0.001), (4) hypertensive vs. non hypertensive pts (RR: 2.26, p=0.002), (5) smokers vs. non smokers (RR: 1.69, p<0.05), (6) pts with HOC over pts with normal homocysteine values (RR: 2.09, p<0.05), (7) pts with increased CRP levels over pts with normal CRP levels (RR: 1.8, p<0.01), (8) pts undergoing HD for 36 vs. 12 months (RR: 1.71, p=0.03), (9) between pts with inadequate or adequate HD (RR: 1.73, p=0.02). No significant correlation existed between CAD incidence and the other risk factors. CONCLUSIONS: Coronary heart disease incidence in elderly HD patients increases with age, male sex, diabetes, SHP, hypertension, increased CRP levels, HOC, smoking, time on HD and inadequacy of HD.