Individual Patient Risk Assessment Research Articles

A frequent functional toll-like receptor 7 polymorphism is associated with accelerated HIV-1 disease progression

Toll-like receptors (TLRs) play an important role in the innate immune response to pathogens. TLR7 recognizes RNA of various viruses including HIV. The objective of this study was to examine the influence of individual genetic variations of TLR7 on the susceptibility to and progression of HIV disease. We genotyped a population of 734 HIV-positive adults and 545 healthy controls for three TLR7 single nucleotide polymorphisms. The frequency of TLR7 genetic variations was assessed and related to HIV disease progression. Furthermore, we analyzed peripheral blood mononuclear cells obtained from healthy individuals differing in their TLR7 genotype and assessed their response to a TLR7-specific ligand ex vivo. Presence of the most frequent TLR7 polymorphism, TLR7 Gln11Leu, was associated with higher viral loads and accelerated progression to advanced immune suppression in HIV patients. Furthermore, in women this polymorphism may be associated with increased HIV-1 susceptibility as it was found more frequently among patients as compared with controls. Peripheral blood mononuclear cells from polymorphism carriers secreted significantly less IFN-alpha following TLR7 activation, whereas IL-6 production remained unaltered. This is the first report of a functional TLR7 variant to be associated with susceptibility to and a more severe clinical course of HIV-1 disease. These results may have implications for the risk assessment of individual patients as well as for HIV-1 therapy and vaccination strategies in the future.

Detection, clinical relevance and specific biological properties of disseminating cancer cells in breast cancer patients.

Abstract Abstract #P2-1 Metastatic relapse of carcinoma patients is mainly due to clinically occult micrometastases present at primary diagnosis, but undetectable even by high-resolution imaging technologies. Frequently, traditional prognostic factors are insufficient to predict metastasis and treatment decisions are mainly based on statistical risk parameters. Highly sensitive and specific cytometric and molecular methods enable now the detection of disseminated tumor cells (DTC) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood of breast carcinoma patients. The presence of DTC has prognostic impact for patients with primary breast cancer with regard to metastatic relapse and overall survival (Braun et al, NEJM 2005) and DTC may even contribute to local relapse (Bidard et al., CCR 2008). However, BM analyses are not well accepted by the medical community for the clinical management patients in breast cancer and other solid tumors. Therefore, most current research efforts are directed to evaluate the clinical utility of CTC detection (Pantel & Panabieres, Nat. Clin Pract. Oncol. 2007). Because of the high variability of results obtained by different cytometric and molecular approaches, standardization of current technologies is urgently required (Fehm et al., Cancer 2006; Riethdorf et al., CCR 2008). While the prognostic significance of CTC could be demonstrated for metastatic breast cancer patients (Hayes & Smerage, CCR 2008), studies on the impact of CTC in primary breast cancer patients are still ongoing but the intermediate results are so far promising (Pantel et al., Nat. Clin Pract. Oncol. In press). Moreover, encouraging results on monitoring CTC during primary systemic or adjuvant chemotherapy in breast cancer patients were obtained in recent studies. Now further characterization of CTC is pivotal to understand the biology of tumor cell dissemination (Pantel et al., Nat. Rev. Cancer 2008). The molecular characterization of CTC with special emphasis on potential cancer stem cell features and therapeutically relevant targets such as HER2 (Wülfing et al., CCR 2006) might improve individual risk assessment and stratification of patients for targeted therapies. This characterization will contribute to more “tailored” and personalized anti-metastatic therapies. At present, the success or failure of anti-cancer therapies is only assessed retrospectively by the absence or presence of overt metastases during the post-operative follow up period. Real-time monitoring of peripheral blood (i.e., during and after systemic adjuvant therapy) for CTC might provide unique information for the clinical management of the individual cancer patient and allow an early change in therapy years before the appearance of overt metastases signals incurability (Panabieres et al., CCR 2008). Future clinical trials will show whether the assessment and monitoring of therapeutic targets (e.g., EGF-R, HER2 or VEGF) on CTC (and probably DTC) might become an important diagnostic tool for cancer patients undergoing targeted therapies and may provide new insights into the selection of tumour cells under biological therapies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr P2-1.

Abstract 5788: VCAM-1 Targeted PET-CT Detects Inflammatory Atherosclerotic Plaques

Hybrid PET-CT imaging of VCAM-1 expression and vascular anatomy may facilitate simultaneous assessment of atherosclerotic lesion biology and morphology, and enhance risk assessment in individual patients. We used combined in vitro/in vivo screening of candidate affinity ligands and developed a PET reporter for imaging VCAM-1 expression with high sensitivity, specificity and translational potential. Three different phage display-derived VCAM-1 affinity peptides were tested using immobilized VCAM-1, VCAM-1 expressing cells and apoE−/− mice. A compound with a linear peptide and arborising tetrameric design showed high affinity (86.6 nM) and specificity for VCAM-1 (97% inhibition with soluble VCAM-1). This lead compound was derivatized with 18Fluorine to synthesize the clinically viable PET agent 18F-4V. In vivo PET-CT imaging showed robust uptake of 18F-4V in plaque laden arterial sections from 8 apoE−/− mice, significantly higher than in 4 wild type mice and attenuated by atorvastatin treatment (p<0.05). 18F-4V uptake was confirmed in excised aortas, colocalized with atherosclerotic plaques delineated by Oil Red O staining and correlated with mRNA levels of VCAM-1 measured by quantitative RT-PCR (R2=0.62, p=0.03). 18F-4V allows noninvasive PET-CT imaging of VCAM-1 in atheromata, has sufficient dynamic range to quantify treatment effects, and correlates with inflammatory gene expression. This approach lends itself to seamless translation to human PET-CT imaging.

A Functional Toll‐Like Receptor 8 Variant Is Associated with HIV Disease Restriction

Toll-like receptors (TLRs) play an important role in the innate immune response to pathogens. TLR8 has been found to recognize RNA derived from various viruses, including human immunodeficiency virus (HIV). Presently, very little is known about the influence of TLR8 genetic variation on susceptibility to and progression of HIV disease. We genotyped a population of 782 HIV-positive adults and 550 healthy control subjects for 3 nonsynonymous TLR8 single-nucleotide polymorphisms. We found that the presence of the most frequent TLR8 polymorphism, TLR8 A1G (rs3764880), confers a significantly protective effect regarding progression of the disease. In overexpression assays, we demonstrated that this receptor variant displays impaired NF-kappaB activation in vitro. Furthermore, we analyzed different cell types obtained from individuals differing in their TLR8 genotype and assessed their response to TLR8 ligands in vitro. The presence of the mutated receptor variant was associated with modulation of cytokine secretion profiles and lipid mediator synthesis patterns in monocytes and neutrophils. This first report of a functional TLR8 variant associated with a different clinical course of an RNA viral disease may have implications for the individual risk assessment of patients infected with HIV and other RNA viruses as well as for future HIV vaccine development.

Follow-up of nonmuscle invasive transitional cell carcinoma of the bladder: how and how often?

Nonmuscle invasive bladder cancer represents a heterogeneous disease due to different natural history of its various appearances. The purpose of this article is to review recent literature regarding follow-up strategies. Management of nonmuscle invasive bladder cancer has become more complex in respect to diagnosis, treatment and follow-up. Follow-up should therefore be based on individual patient-risk assessment. In addition to improved diagnosis by fluorescence-guided cystoscopy and other new diagnostic tools like optical-coherence tomography management has concentrated on optimizing different concepts of intravesical therapy. The intent of nonmuscle invasive bladder cancer management is to control recurrence and progression and to identify invasive tumours at the earliest possible stage. To obtain exact staging, besides a proper transurethral resection of bladder, a restaging transurethral resection of bladder should be performed in T1 patients. Data from the literature supports the immediate postoperative intravesical instillation of different chemotherapeutic agents in low-risk patients. Multifocal papillary lesions might necessitate a more intensive adjuvant regimen, whereas intravesical immunotherapy using bacillus Calmette-Guerin is recommended in patients who are at a high-risk of progression. Early cystectomy should be considered in patients with recurrent T1 tumours or refractory carcinoma in situ to avoid unfavourable tumour progression.

Midregional pro-atrial natriuretic peptide as a prognostic marker in pneumonia

To evaluate the usefulness of midregional pro-atrial natriuretic peptide (MR-proANP) measurement in the stratification of severity in community-acquired pneumonia. The population studied was three hundred patients admitted to Emergency Department of a tertiary university hospital presenting clinical signs of lower respiratory tract infection, a new infiltrate on the chest radiograph and a confirmed pneumonia by clinical evolution. Patients were stratified by the Pneumonia Severity Index (PSI), by CURB-65 score and by the development of complications. Serum samples were obtained at the moment of admission and prior to antibiotic therapy, and stored until analysis. MR-proANP was measured by B.R.A.H.M.S MR-proANP KRYPTOR. Serum levels of MR-proANP increased with the severity of pneumonia, according to PSI score and CURB-65 score. Median MR-proANP levels were significantly higher (p<0.0001) in patients with high PSI risk class (IV-V) than in those with low PSI risk class (I-III). MR-proANP levels were also significantly higher (p=0.029) in those patients that developed complications or died. There was no association between MR-proANP and etiology of pneumonia and the radiographic extent. We can conclude that MR-proANP measurement was helpful for individual risk assessment in patients with pneumonia admitted to the emergency department.

Breast radiation dose estimates compared to measured doses from involved field radiotherapy (IFRT) or mantle fields for early stage Hodgkin lymphoma (ESHL)

18503 Background Breast cancer risk after mantle irradiation has prompted concern regarding the use of IFRT for ESHL. As breast cancer risk is radiation dose related, reliable estimates of breast radiation dose from IFRT might aid individual patient risk assessment. However, estimates of breast dose from radiation scatter/leakage beyond the involved field, using standard computer algorithms, are of uncertain accuracy. The aims of this study were to compare computer estimates with measured breast dose, and to compare breast dose from mantle and neck IFRT. Methods A phantom with breast tissue equivalent was used to determine breast dose using computerized treatment planning (CMS XiO), and to perform measurements within the phantom breast tissue using thermoluminescent dosimetry (TLD). These measurements were made for mantle fields and (neck) IFRT. Results Computer estimates and TLD measurements of breast dose in centigray (cGY) are shown for IFRT and mantle treatment, for a prescribed dose of 3000cGy, using 6MV X-rays from a Varian 21eX linear accelerator. Conclusions Breast dose from neck IFRT was lower than from mantle treatment by an order of magnitude, but being well outside the treatment field, was not accurately estimated by our computer algorithm. Work in progress will examine breast dose from mediastinal IFRT and involved node irradiation. Modifications to the planning algorithm may improve accuracy of dose estimates at a distance from the primary field, allowing routine breast dose estimates for patients. Ultimately, utilisation of dose-risk data may allow risk modelling and risk-benefit analysis of IFRT for ESHL in individual patients. [Table: see text] No significant financial relationships to disclose.

High C-reactive protein and low cholesterol levels are prognostic markers of survival in severe sepsis

Study Objective To evaluate serum C-reactive protein and cholesterol as a prognostic factor for survival in patients with severe sepsis. Design Prospective study. Setting University hospital. Patients The study population consisted of 96 patients (age range, 18-75 years; median, 56 years; men/women ratio, 40:56) in whom severe sepsis was diagnosed. Interventions Patients' serum levels of C-reactive protein and cholesterol were measured upon admission to an intensive care unit, two days later, and on the day of discharge from the intensive care unit or on the day of death. Measurements and Main Results Cholesterol levels were significantly lower among the nonsurviving patients (day 1, 92.2 ± 25.1 mg/dL; day 2, 92.1 ± 21.7 mg/dL; death/discharge day, 92.2 ± 21.7 mg/dL) than surviving patients (day 1, 175.1 ± 38.6 mg/dL [ P < 0.001]; day 2, 173.0 ± 39.3 mg/dL [ P < 0.001]; death/discharge day, 171.8 ± 39.6 mg/dL [ P = 0.010]). Median C-reactive protein levels were significantly higher among the nonsurvivors (day 1, 32 mg/dL [range, 20.5-64.5 mg/dL]; day 2, 33 mg/dL [range, 22-74.5 mg/dL]; death/discharge day, 30 mg/dL [range, 22-57 mg/dL]) than survivors (day 1, 10 mg/dL [range, 6-14 mg/dL]; day 2, 9 mg/dL [range, 5-10 mg/dL]; death/discharge day, 6 mg/dL [range, 3-9 mg/dL]; P < 0.001). Conclusion Serum C-reactive protein and cholesterol are a predictor of survival in patients with severe sepsis. Low cholesterol and high C-reactive protein levels appear as a valuable tool for individual risk assessment in severe sepsis patients and for stratification of high-risk patients in future intervention trials.

Prophylaxe des kontrastmittelinduzierten Nierenversagens

The increasing use of iodine-based contrast media for diagnostic and therapeutic interventions is associated with the risk of contrast media-induced acute kidney injury with a significant impact on patient morbidity and mortality as well as healthcare expenditure. To reduce patient risk, strict indications as well as the assessment of individual risk profiles and the use of effective renoprotective regimen are required. Reducing contast media exposure, the use of low-osmolar agents, hydration with isotonic saline and N-acetylcysteine have proven effective in the prevention of contrast media-induced acute kidney injury. In contrast, postinterventional hemodialysis for removal of contrast media from the circulation has been without benefit regarding renal and patient outcome and is not generally recommended. An algorithm for assessment of individual patient risk and a summary of current concepts in the prevention of contrast media-induced acute kidney injury is provided.

Estimating survival probability in stage III melanoma: A multivariable individualized patient risk assessment nomogram

8020 Background: Recent revisions in the AJCC staging system have increased its complexity without comparable improvement in prognostic accuracy for patients with Stage III melanoma. Furthermore, there remains significant prognostic heterogeneity, even within Stages IIIA, IIIB, and IIIC. The current study was undertaken to develop a model for individual patient risk assessment, both to facilitate patient care, and to help define prognostically homogeneous patient populations for entry into clinical trials. Methods: Patients with AJCC Stage III melanoma were identified from a prospective single institution database. Overall survival was calculated from the date of Stage III to last followup. A multivariate Cox model of independent prognostic factors was developed, and a multivariable individualized patient risk assessment nomogram was built from that model. Results: Among 1,064 patients with Stage III melanoma, 535 have died, at a median followup of 44 months. Independent predictors of overall survival are shown in the table. Individual patient three and five year survival was predicted by incorporating all eight variables into a prognostic nomogram. The nomogram was superior to the AJCC Staging system in predicting outcome in Stage III melanoma patients. Conclusions: Individual patient risk assessment is more accurate than traditional AJCC staging in predicting outcome in Stage III melanoma. This approach, which can be easily incorporated into a handheld computing environment, offers potential advantages for both patient care and clinical research, and should be explored in the next iteration of the AJCC staging system. [Table: see text] No significant financial relationships to disclose.

Gene expression profiles and molecular classification to predict distant metastasis and tamoxifen-resistant breast cancer

Genome-wide measures of gene expression can identify patterns of gene activity that subclassify tumours and might provide better means than are currently available for individual risk assessment in patients with primary breast cancer and for prediction of tamoxifen resistance.

Bladder cancer

This article reviews the recent literature concerning important issues in the management of patients with bladder cancer. A brief overview of all aspects of bladder cancer including the etiology, diagnosis, and treatment are discussed with a focus on recent advances. Bladder cancer is a significant cause of morbidity and mortality. The treatment for bladder cancer should be based on individual patient risk assessment and should include a multidisciplinary approach. In patients with superficial bladder cancer, research has focused on improving and optimizing intravesical therapy to reduce tumor recurrence and progression as well as on methods to better select the most appropriate treatment for patients with high-risk features. The important prognostic and therapeutic role of lymphadenectomy during radical cystectomy has become apparent and recent work has attempted to better define what should be considered the standard for lymph node dissection. Finally, in an attempt to improve survival, advances have been made using systemic chemotherapy in both the perioperative settings as well as for treatment of metastatic bladder cancer. Research continues to improve our understanding of bladder cancer. This ongoing investigation is currently being translated to the bedside with refinements in the diagnosis and treatment of patients with bladder cancer.

A novel BRCA2 mutation in an Indonesian family found with a new, rapid, and sensitive mutation detection method based on pooled denaturing gradient gel electrophoresis and targeted sequencing

Background: Breast cancer is increasing in Indonesia and other developing countries. Germline mutations in the BRCA1/2 genes are most strongly associated with a high risk for breast cancer development. There...

Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer

<h2>Summary</h2><h3>Background</h3> Genome-wide measures of gene expression can identify patterns of gene activity that subclassify tumours and might provide a better means than is currently available for individual risk assessment in patients with lymph-node-negative breast cancer. <h3>Methods</h3> We analysed, with Affymetrix Human U133a GeneChips, the expression of 22 000 transcripts from total RNA of frozen tumour samples from 286 lymph-node-negative patients who had not received adjuvant systemic treatment. <h3>Findings</h3> In a training set of 115 tumours, we identified a 76-gene signature consisting of 60 genes for patients positive for oestrogen receptors (ER) and 16 genes for ER-negative patients. This signature showed 93% sensitivity and 48% specificity in a subsequent independent testing set of 171 lymph-node-negative patients. The gene profile was highly informative in identifying patients who developed distant metastases within 5 years (hazard ratio 5·67 [95% CI 2·59–12·4]), even when corrected for traditional prognostic factors in multivariate analysis (5·55 [2·46–12·5]). The 76-gene profile also represented a strong prognostic factor for the development of metastasis in the subgroups of 84 premenopausal patients (9·60 [2·28–40·5]), 87 postmenopausal patients (4·04 [1·57–10·4]), and 79 patients with tumours of 10–20 mm (14·1 [3·34–59·2]), a group of patients for whom prediction of prognosis is especially difficult. <h3>Interpretation</h3> The identified signature provides a powerful tool for identification of patients at high risk of distant recurrence. The ability to identify patients who have a favourable prognosis could, after independent confirmation, allow clinicians to avoid adjuvant systemic therapy or to choose less aggressive therapeutic options.

Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer

Genome-wide measures of gene expression can identify patterns of gene activity that subclassify tumours and might provide a better means than is currently available for individual risk assessment in patients with lymph-node-negative breast cancer. We analysed, with Affymetrix Human U133a GeneChips, the expression of 22000 transcripts from total RNA of frozen tumour samples from 286 lymph-node-negative patients who had not received adjuvant systemic treatment. In a training set of 115 tumours, we identified a 76-gene signature consisting of 60 genes for patients positive for oestrogen receptors (ER) and 16 genes for ER-negative patients. This signature showed 93% sensitivity and 48% specificity in a subsequent independent testing set of 171 lymph-node-negative patients. The gene profile was highly informative in identifying patients who developed distant metastases within 5 years (hazard ratio 5.67 [95% CI 2.59-12.4]), even when corrected for traditional prognostic factors in multivariate analysis (5.55 [2.46-12.5]). The 76-gene profile also represented a strong prognostic factor for the development of metastasis in the subgroups of 84 premenopausal patients (9.60 [2.28-40.5]), 87 postmenopausal patients (4.04 [1.57-10.4]), and 79 patients with tumours of 10-20 mm (14.1 [3.34-59.2]), a group of patients for whom prediction of prognosis is especially difficult. The identified signature provides a powerful tool for identification of patients at high risk of distant recurrence. The ability to identify patients who have a favourable prognosis could, after independent confirmation, allow clinicians to avoid adjuvant systemic therapy or to choose less aggressive therapeutic options.

Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study

IntroductionMeasurement of biomarkers is a potential approach to early assessment and prediction of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) levels in a cohort of medical intensive care patients and to compare it with other biomarkers and physiological scores.MethodWe evaluated blood samples from 101 consecutive critically ill patients admitted to the intensive care unit and from 160 age-matched healthy control individuals. The patients had initially been enrolled in a prospective observational study investigating the prognostic value of endocrine dysfunction in critically ill patients ("PEDCRIP" Study). The prognostic value of MR-proADM levels was compared with those of two physiological scores and of various biomarkers (for example C-reactive Protein, IL-6, procalcitonin). MR-proADM was measured in EDTA plasma from all patients using a new sandwich immunoassay.ResultsOn admission, 53 patients had sepsis, severe sepsis, or septic shock, and 48 had systemic inflammatory response syndrome. Median MR-proADM levels on admission (nmol/l [range]) were 1.1 (0.3–3.7) in patients with systemic inflammatory response syndrome, 1.8 (0.4–5.8) in those with sepsis, 2.3 (1.0–17.6) in those with severe sepsis and 4.5 (0.9–21) in patients with septic shock. In healthy control individuals the median MR-proADM was 0.4 (0.21–0.97). On admission, circulating MR-proADM levels in patients with sepsis, severe sepsis, or septic shock were significantly higher in nonsurvivors (8.5 [0.8–21.0]; P < 0.001) than in survivors (1.7 [0.4–17.6]). In a receiver operating curve analysis of survival of patients with sepsis, the area under the curve (AUC) for MR-proADM was 0.81, which was similar to the AUCs for IL-6, Acute Physiology and Chronic Health Evaluation II score and Simplified Acute Physiology Score II. The prognostic value of MR-proADM was independent of the sepsis classification system used.ConclusionMR-proADM may be helpful in individual risk assessment in septic patients.

Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study

IntroductionAdditional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores.MethodsBlood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay.ResultsOn admission, 53 patients had sepsis, severe sepsis, or septic shock, and 68 had systemic inflammatory response syndrome. The median pro-ANP value in the survivors was 194 pmol/l (range 20–2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100–2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in surviving than in nonsurviving sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score.ConclusionPro-ANP appears to be a valuable tool for individual risk assessment in sepsis patients and for stratification of high-risk patients in future intervention trials. Further studies are needed to validate our results.

Single step high-throughput determination of Toll-like receptor 4 polymorphisms

Background: Toll-like receptors are central components of host defence in humans, responsible for recognition of pathogen-associated molecular patterns and activation of innate immunity. Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS) and other microbial components, thereby initiating the expression and release of pro-inflammatory cytokines. The common, frequently co-segregating allelic variants Asp299Gly and Thr399Ile have been related to susceptibility to gram-negative infections and sepsis and may be involved in the development of atherosclerosis. Identification of TLR4 Asp299Gly and Thr399Ile genotypes can be important for examination of genotype/phenotype relationships as well as for individual risk assessment of patients. Methods: TLR4 Asp299Gly and Thr399Ile genotypes were detected by a single tube polymerase chain reaction (PCR), based on exonuclease degradation of dual labelled allele-specific oligonucleotides. The assay results were compared with conventional restriction fragment length polymorphism (RFLP) analysis. Results: Genotypes of 345 individuals were determined simultaneously in a single PCR assay. Allele frequencies for our population were 6.8% for the TLR4 Asp299Gly polymorphism and 6.4% for the Thr399Ile polymorphism. Validation by RFLP analysis revealed a correct detection of all genotypes. Conclusions: We have developed a novel method for the detection of the TLR4 Asp299Gly and Thr399Ile mutations, permitting rapid genotyping which should be useful for large-scale population studies as well as applicable for routine clinical testing.

Cardiovascular risk assessment in individual patients from carotid intimal-medial thickness measurements

Carotid intimal-medial thickness measurements are a low-cost, noninvasive method to assess atherosclerotic burden in the general population. A large evidence base exists to validate estimates of absolute cardiovascular risk obtained from measurements of carotid intimal-medial thickness. Precise and reliable carotid intimal-medial thickness measurements from several ultrasonic interrogation angles and anatomic sites are required to obtain the most valid estimates of cardiovascular risk in an individual patient. This paper reviews basic measurement concepts and outlines important considerations in the clinical assessment of absolute cardiovascular risk in individual patients from measurements of carotid intimal-medial thickness.

Microalbuminuria

Microalbuminuria