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PubMed2005

B-type natriuretic peptide as an integrated risk marker in non-ST elevation acute coronary syndromes.

BACKGROUND: Elevated B-type natriuretic peptide (BNP) levels show prognostic significance in patients with non-ST elevation acute coronary syndromes, but the underlying pathophysiology remains unclear. METHODS: Two hundred and eighteen consecutive patients with non-ST elevation acute coronary syndromes were studied retrospectively. We compared clinical characteristics between groups with plasma BNP levels above or below the median value, and performed multiple logistic regression analysis to identify independent predictors of supramedian BNP levels. RESULTS: Patients with supramedian BNP (>or=134 pg/ml) were more likely to be elderly (>or=75 years) with diabetes, prior myocardial infarction, and a history of coronary artery bypass grafting. They also had higher cardiac marker levels, a higher Killip class, a lower left ventricular ejection fraction, renal insufficiency (creatinine>or=1.5 mg/dl), and more 3-vessel disease. In multivariate analysis, the strongest independent predictor of supramedian BNP levels was 3-vessel disease (chi(2)=12.1), followed by old age (chi(2)=10.3), renal insufficiency (chi(2)=5.0), higher Killip class (chi(2)=4.2), and lower left ventricular ejection fraction (chi(2)=4.1). All 11 patients dying in hospital had supramedian BNP levels. Its elevation reflected the risk of 3-vessel disease and coronary artery bypass grafting regardless of troponin status. CONCLUSION: In unselected patients with non-ST elevation acute coronary syndromes, an increase of BNP is correlated with the extent of myocardial ischemia, age, renal insufficiency, and ventricular dysfunction. It may be a useful biomarker integrating conventional risk factors for risk stratification in this population.

Aged↗

PubMed2005

Assessment of HPA-axis function in posttraumatic stress disorder: pharmacological and non-pharmacological challenge tests, a review.

Posttraumatic stress disorder (PTSD) is typically accompanied by acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but several studies have also used a challenge model to further assess the role of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. This paper reviews common methodology and research findings on HPA function in PTSD, and discusses the pathophysiological mechanisms underlying these findings. We reviewed the literature and selected all English-language, human subject, data driven, pharmacological and non-pharmacological challenge studies pertaining to the HPA axis, and in vitro leukocyte glucocorticoid receptor studies in adult PTSD subjects. Studies using a non-pharmacological stress paradigm (cognitive stress, trauma reminders) to stimulate the HPA axis showed an exaggerated cortisol response in PTSD. The most widely used pharmacological challenge with consistent results was the low dose dexamethasone-suppression test (DST). These DST studies showed enhanced cortisol suppression in subjects with PTSD. Different hypotheses have been purported to explain the alterations in HPA axis functioning in PTSD. The results of the reviewed challenge tests, however, did not exclusively support one of the hypothesized mechanisms. Further research assessing hormones at all levels of the HPA axis at both baseline and at challenge conditions with a proper stratification of study population, will be necessary for a better understanding of stress-responsivity on the level of the HPA axis in PTSD.

Cognition↗

PubMed2004

Noninvasive in vivo detection of prognostic indicators for high-risk uveal melanoma: ultrasound parameter imaging.

PURPOSE: Primary malignant melanoma of the choroid and ciliary body has traditionally been treated without histologic staging, using purely clinical indicators. The presence of extravascular matrix patterns (EMP) in histologic sections of uveal melanoma has been shown to be an independent indicator of metastatic risk. These patterns are of a dimension and physical composition that are likely to be detected with ultrasound backscatter analysis. Our aim was to determine whether ultrasound parameter imaging could detect the presence of EMP at a diagnostically significant level for treatment staging and for planning investigational studies of therapeutic modalities. DESIGN: Prospective, masked ultrasound-pathologic correlative study. PARTICIPANTS: One hundred seventeen patients diagnosed with previously untreated choroidal melanoma were scanned within 2 weeks before enucleation. METHODS: Tumors were evaluated histologically and divided into high-risk and low-risk groups on the basis of the presence of 2% or more histologic cross-sectional area composed of EMP patterns. Digital ultrasound data were processed to generate parameter images representing the size and concentration of ultrasound scatterers. Histologic and ultrasound images and data were correlated, and linear and nonlinear statistical methods were used to create multivariate models for noninvasive differentiation of high-risk and low-risk tumors. MAIN OUTCOME MEASURES: Presence or absence of high-risk EMP and associated ultrasound parameter classification models. RESULTS: Of the 117 tumors, 69 were classified as low risk, and 48 were classified as high-risk with histologic analysis. A classification that used ultrasound parameter image features with linear discriminant analysis could correctly identify 79.5% of cases retrospectively and 75.2% of cases by use of cross-validation, an estimate of prospective classification ability. By use of a more powerful classification technique (support vector machine), 93.1% of cases were correctly classified retrospectively. With a cross-validation procedure, 80.10% of cases were correctly classified. CONCLUSIONS: Ultrasound can be used noninvasively to classify tumors into high-risk and low-risk groups by detecting the presence of EMP patterns. By the use of previous studies that compared the histologic presence of EMP patterns with patient survival, estimates of hazard rates associated with ultrasound risk groups can be made. The noninvasive ultrasound classification is potentially useful as a prognostic variable and as a tool for stratification of patient populations for tumor treatment evaluation.

Eye Enucleation↗

PubMed2001

Defining severe community-acquired pneumonia.

Based on the recognition of the main pathophysiologic features of pneumonia and currently available data on prognosis and clinical severity assessment, key points for a definition of severe pneumonia are as follows: 1. Independent predictors of pneumonia severity are factors reflecting acute respiratory failure and severe sepsis or septic shock. 2. In view of the dependence of the development of acute respiratory failure on pulmonary comorbidities, radiographic extension may prove to be an additional independent predictor of severe respiratory compromise. 3. Vital sign abnormalities other than acute respiratory failure and severe hypotension may be independent predictors of severity, particularly in patients presenting in early and asymptomatic stages of severe sepsis. 4. Several pathogens have been shown to have adverse prognostic potential. Because the cause is unknown at the initial evaluation, however, pathogens cannot form part of the criteria for the initial severity assessment. 5. Because pneumonia is a dynamic process, any assessment of severity takes place at an arbitrary point of disease evolution. It would be desirable to define a set of parameters reflecting initial severity as well as a state of increased risk for early deterioration toward severe pneumonia. 6. Severity stratification within the population of patients with severe pneumonia may open the prospect of identifying patients who may have the greatest benefit from intensive care.

Age Factors↗

PubMed2001

Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Retinal microvascular abnormalities reflect damage from hypertension and other vascular processes. We examined the relation of such abnormalities to incident stroke. METHODS: A cohort of 10358 men and women (aged 51 to 72 years) living in four US communities underwent retinal photography and standard grading for retinal microvascular abnormalities. The calibres of all retinal arterioles and venules were measured after digital conversion of the photographs, and a summary arteriole-to-venule ratio (AVR) was calculated as an index of arteriolar narrowing (smaller AVR indicates greater narrowing). Cases of incident stroke admitted to hospital were identified and validated by case record reviews. FINDINGS: Over an average of 3.5 years, 110 participants had incident strokes. After adjustment for age, sex, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, most retinal microvascular characteristics were predictive of incident stroke, with adjusted relative risks of 2.58 (1.59-4.20) for any retinopathy, 3.11 (1.71-5.65) for microaneurysms, 3.08 (1.42-6.68) for soft exudates, 2.55 (1.27-5.14) for blot haemorrhages, 2.26 (1.00-5.12) for flame-shaped haemorrhages, and 1.60 (1.03-2.47) for arteriovenous nicking. The relative risk of stroke increased with decreasing AVR (p=0.03). The associations were similar for ischaemic strokes specifically, and for strokes in individuals with hypertension, either with or without diabetes. INTERPRETATION: Retinal microvascular abnormalities are related to incident stroke. The findings support a microvascular role in the pathogenesis of stroke. They suggest that retinal photography may be useful for cerebrovascular-risk stratification in appropriate populations.

Arteriosclerosis↗

PubMed2000

Cytokines in genetic susceptibility to multiple sclerosis: a candidate gene approach. French Multiple Sclerosis Genetics Group.

The immune system is involved in the pathophysiology of multiple sclerosis (MS) but the initiating antigen(s) is not yet identified. Since cytokines control both the intensity and the quality of the immune response they may be relevant candidates for the genetic susceptibility to MS. To analyze the contribution of type 1 and type 2 cytokine and cytokine receptor genes in the genetic susceptibility to MS, we have examined, in 116 French MS sibpairs, whether there is significant linkage between MS and 15 cytokine or cytokine receptor genes using 31 highly polymorphic genetic markers. The data were analyzed using the maximum likelihood score and the transmission disequilibrium approaches. None of the candidate genes tested was significantly linked to MS on the whole population. However, after stratification of the analysis on the basis of sharing (or not) of the HLA-DRB1*1501 allele, indication of linkage was found for the IL2-RB gene. These findings suggest that the IL2-RB locus contributes to the genetic susceptibility in a subgroup of MS patients.

Cytokines↗

PubMed2003

The methodology of HIV/AIDS impact studies: a review of current practices.

This review of studies on the socio-economic impact of HIV/AIDS shows that diversity in methodological design, which often is a result of practical considerations and resource constraints rather than of poor design, is the norm. This limits the comparability of research findings. More detailed reporting on method, which is not the norm, can go some way towards facilitating such comparison. Furthermore, the review underlines the importance of exploring intervention issues in more detail. Researchers need to employ results in answering specific policy questions. Scope remains for more impact studies to be conducted in developing countries in general and in certain high prevalence countries in specific, i.e. Southern Africa. Studies that explore the urban/rural dynamics of and clients' perceptions and behavior in seeking care and support are necessary to better understand the epidemic. The role of community-based organizations, non-governmental organizations and other stakeholders in studies of this nature can be expanded. Larger studies generally have more statistical power, but smaller, in-depth studies can be equally valuable. A careful stratification of sample populations can enhance the quality of cross-sectional studies. Qualitative methods should be used to complement the current reliance on survey-based methods of data collection. More longitudinal studies are required to explore the long-term impacts of HIV/AIDS. HIV/AIDS training for fieldworkers should be standard in studies of this nature, while cognizance should be taken of the dangers of employing local people as fieldworkers in studies of such sensitive nature. Scope remains for the further empirical analysis of data from impact studies, which requires these data sets being made accessible to more researchers. In the longer term, an attempt at standardizing core modules in impact studies can help to improve our understanding of the impact of HIV/AIDS in different settings.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Digging the genome for diabetes mellitus: the 2nd ADA Research Symposium on the Genetics of Diabetes, San Jose, CA, USA, 17-19 October 1999.

The diabetes genetics community recently met in California to discuss the impact that the latest findings in susceptibility mapping might have on our understanding of the pathophysiology of diabetes mellitus and its long-term complications. Organized by Ralph DeFronzo (San Antonio, TX) and Alan Permutt (St Louis, MO) the symposium covered the genetics of type 1 and type 2 diabetes, obesity, approaches to population selection and stratification, quantitative trait analysis, epidemiological tools and technological advances in genotyping.

Biotechnology↗

PubMed2006

Can delivery room management impact the length of hospital stay in premature infants?

OBJECTIVES: To evaluate the impact of initiating early nasal continuous positive airway pressure (ENCPAP) on the length of hospital stay (LOS) for the very low birth weight (VLBW) infants. STUDY DESIGN: LOS at the George Washington University Hospital (GW) after the institution of ENCPAP policy was compared to benchmark values using two-tail t-tests. The incidence of neonatal morbidity was calculated using Bonferroni corrected 95% confidence interval as compared to benchmark rates (alpha=0.001). Comparisons were repeated after stratification of the population into four birth weight subcategories: group A (GrpA) (501 to 750 g), GrpB (751 to 1000 g), GrpC (1001 to 1250 g) and GrpD (1251 to 1500 g). RESULTS: We studied 228 consecutive VLBW infants (birth weight: 995+/-294 g and gestational age: 27.7+/-2.7 weeks). Compared to benchmark values, the GW experience was associated with a significant reduction of 5.1 days in LOS (55.9+/-25.2 vs 61+/-32 days; P=0.04). The decrease in LOS was consistent in all subgroups, but was most noticeable in infants of the smallest weight subcategory (LOS in GrpA=86+/-21 vs 104+/-32, P=0.004; in GrpB=69.9+/-16.7 vs 79+/-27, P=0.018; in GrpC=48.2+/-13 vs 56+/-22, P<0.001 and in GrpD=31.7+/-12.5 vs 40+/-19, P=0.003). In the overall population, a lower incidence of chronic lung disease (CLD) (17.8 vs 29%, P<0.001) was also noted. There were no differences in mortality rates (9 vs 14%), or the incidence of necrotizing enterocolitis (NEC) (8 vs 6%) or intraventricular hemorrhage (6.2 vs 9%) between GW and the established benchmark rates. CONCLUSION: ENCPAP may reduce LOS in VLBW infants in our study population. This relatively shorter LOS was associated with a lower incidence of CLD, which may be a contributing factor.

Continuous Positive Airway Pressure↗

PubMed2006

Prognostic factors for hyperdiploid-myeloma: effects of chromosome 13 deletions and IgH translocations.

Chromosomal hyperdiploidy is the defining genetic signature in 40-50% of myeloma (MM) patients. We characterize hyperdiploid-MM (H-MM) in terms of its clinical and prognostic features in a cohort of 220 H-MM patients entered into clinical trials. Hyperdiploid-myeloma is associated with male sex, kappa immunoglobulin subtype, symptomatic bone disease and better survival compared to nonhyperdiploid-MM (median overall survival 48 vs 35 months, log-rank P = 0.023), despite similar response to treatment. Among 108 H-MM cases with FISH studies for common genetic abnormalities, survival is negatively affected by the existence of immunoglobulin heavy chain (IgH) translocations, especially those involving unknown partners, while the presence of chromosome 13 deletion by FISH did not significantly affect survival (median overall survival 50 vs 47 months, log-rank P = 0.47). Hyperdiploid-myeloma is therefore a unique genetic subtype of MM associated with improved outcome with distinct clinical features. The existence of IgH translocations but not chromosome 13 deletion by FISH negatively impacts survival and may allow further risk stratification of this population of MM patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

High prevalence of undiagnosed coeliac disease in adults: a Swedish population-based study.

OBJECTIVE: To determine the prevalence of coeliac disease in a population-based sample of Swedish adults. DESIGN: Population-based cross-sectional study. SETTING: Northern Sweden. SUBJECTS: A total of 1894 adults (76%) out of 2500 invited, randomly selected from the population register after stratification for age and sex. MAIN OUTCOME MEASURES: Prevalence of biopsy verified coeliac disease, symptoms of undiagnosed cases, and results of antiendomysium and antigliadin serum antibody tests. RESULTS: Coeliac disease was confirmed by intestinal biopsy showing enteropathy in 10 individuals (seven women and three men), corresponding to a prevalence of 5.3 per 1000 (95% CI = 2.5-9.7). The majority of cases (eight out of 10) had not been diagnosed prior to the screening, although many had symptoms compatible with coeliac disease. All individuals with antiendomysium antibody positivity who were subjected to a small intestinal biopsy had enteropathy. Furthermore, all of them also had elevated levels of antigliadin antibodies type IgA and/or IgG. CONCLUSIONS: Coeliac disease is common, albeit mostly undiagnosed, in Swedish adults. It is likely that the situation is no better in other countries. This highlights the importance of keeping coeliac disease in mind, and of promptly investigating individuals with unexplained, even mild, symptoms compatible with the disease. Serological markers, e.g. antigliadin and antiendomysium antibodies, are useful tools within this active case-finding strategy, although the final diagnosis should be based on an intestinal biopsy demonstrating enteropathy.

Adult↗

PubMed2001

Screening for adult coeliac disease - which serological marker(s) to use?

OBJECTIVE: To determine which serological marker(s) to use when screening for coeliac disease. DESIGN: In a population-based cross-sectional study we compared the use of antigliadin antibodies (AGA) of isotypes IgA and IgG, antiendomysial antibodies (AEA) of isotype IgA and antitransglutaminase antibodies (ATGA) of isotype IgA for detecting coeliac disease amongst adults. SETTING: Northern Sweden. SUBJECTS: A total of 1850 of 2500 (74%) invited adults (aged 25-74 years) who were randomly selected from the population register after stratification for age and sex. MAIN OUTCOME MEASURES: The sensitivity, specificity and predictive values of the AGA, ATGA and AEA tests. RESULTS: Nine cases of biopsy proven, previously undiagnosed coeliac disease were detected by screening. The sensitivity of both ATGA and AEA was 100% whilst AGA IgA and IgG both had a sensitivity of 89%. The AEA test had a specificity of 100% whereas the specificities of the ATGA, AGA IgA and IgG tests were 97, 96 and 78%, respectively. The positive predictive value for the AEA test was 100%, whereas it was considerably lower for the other tests (ATGA > AGA IgA > AGA IgG), with further decreases for all tests when shifting from a clinical to a screening situation. CONCLUSIONS: When screening for coeliac disease we suggest a serial testing approach, i.e. an initial ATGA test and, when positive, followed by an AEA test, provided that IgA deficiency has been excluded. However, assessment of the small intestinal mucosal morphology is still required to ascertain the diagnosis.

Adult↗

PubMed2006

Targeted therapy for renal cell carcinoma: a new therapeutic paradigm.

Renal cell carcinoma is the most common tumor of the kidney. It has an unpredictable behavior and poor response to systemic therapy. Developing newer therapy for this disease is a priority considering the high recurrence rate and the small subset of patients who benefit from the use of cytokines such as interferon-alpha or interleukin-2. Identifying molecular targets and targeting various biomarkers has revolutionized the therapeutic approach to advanced and metastatic renal cell carcinoma. Although some of the antiangiogenic agents and receptor tyrosine kinase inhibitors appear promising, further understanding of their mechanism of action and the patient population who would benefit most from such agents is still being explored. As numerous targeted agents are entering the clinical investigation arena in a relatively short period of time, newer challenges in renal cell carcinoma therapeutics are emerging. Some of the future challenges in using targeted antineoplastic agents in renal cell carcinoma will include evaluating their long-term safety and benefit, using the particular drug in the appropriate patient population after appropriate stratification and studying the combination of some of these drugs for synergy or additive effects.

Antineoplastic Agents↗

PubMed1998

A comparative study of sibship tests of linkage and/or association.

Population-based tests of association have used data from either case-control studies or studies based on trios (affected child and parents). Case-control studies are more prone to false-positive results caused by inappropriate controls, which can occur if, for example, there is population admixture or stratification. An advantage of family-based tests is that cases and controls are well matched, but parental data may not always be available, especially for late-onset diseases. Three recent family-based tests of association and linkage utilize unaffected siblings as surrogates for untyped parents. In this paper, we propose an extension of one of these tests. We describe and compare the four tests in the context of a complex disease for both biallelic and multiallelic markers, as well as for sibships of different sizes. We also examine the consequences of having some parental data in the sample.

Alleles↗

PubMed2003

Using the noninformative families in family-based association tests: a powerful new testing strategy.

For genetic association studies with multiple phenotypes, we propose a new strategy for multiple testing with family-based association tests (FBATs). The strategy increases the power by both using all available family data and reducing the number of hypotheses tested while being robust against population admixture and stratification. By use of conditional power calculations, the approach screens all possible null hypotheses without biasing the nominal significance level, and it identifies the subset of phenotypes that has optimal power when tested for association by either univariate or multivariate FBATs. An application of our strategy to an asthma study shows the practical relevance of the proposed methodology. In simulation studies, we compare our testing strategy with standard methodology for family studies. Furthermore, the proposed principle of using all data without biasing the nominal significance in an analysis prior to the computation of the test statistic has broad and powerful applications in many areas of family-based association studies.

Analysis of Variance↗

PubMed2026

Genomic hallmarks of depot medroxyprogesterone acetate-associated meningiomas.

BACKGROUND: Population-based studies have linked progestin exposure to increased meningioma risk. However, the molecular basis of meningiomas associated with depot medroxyprogesterone acetate (DMPA)-a common injectable contraceptive-remains undefined. METHODS: We performed an integrated clinicopathologic and genomic analysis of meningiomas from 10 women with long-term DMPA exposure. Tumors underwent histopathological analysis, targeted sequencing, and DNA methylation profiling. Data were integrated with reference cohorts (Baylor and Heidelberg) and analyzed through classifier assignment, consensus clustering, copy number analysis, differential methylation testing, and dimensionality reduction. RESULTS: Depot medroxyprogesterone acetate-associated meningiomas were all newly diagnosed, World Health Organization grade 1 tumors with a predilection for the anterior and central skull base (n = 6). Nine patients harbored multiple meningiomas. Four experienced regression of untreated meningiomas following DMPA cessation, while 5 demonstrated stabilization. Histopathology demonstrated relative overrepresentation of metaplastic morphology, an uncommon meningioma subtype. All DMPA-associated meningiomas mapped to benign molecular groups, and most exhibited low copy number alteration burden. Targeted sequencing revealed enrichment for TRAF7 mutations (n = 5), with no NF2 mutations detected. Eight tumors shared consensus cluster identity, with cohesive grouping on principal component analysis and t-distributed stochastic neighbor embedding. No differential methylation was identified at the progesterone receptor locus. CONCLUSIONS: Depot medroxyprogesterone acetate-associated meningiomas represent a recognizable phenotype within the broader NF2-wildtype/TRAF7-enriched spectrum of benign meningiomas, characterized by chromosomal stability, a shared methylation profile, tumor multiplicity, and regression or stabilization following DMPA cessation. While derived from a small single-institution cohort, these findings provide a molecular framework for understanding progestin-associated meningioma biology, reinterpreting epidemiologic literature, and informing population-level risk stratification.

Humans↗

PubMed2002

The era of genomics: impact on sepsis clinical trial design.

OBJECTIVE: This article aims to address the predictable impact of genetics on the design of clinical trials in the field of critical care medicine, with emphasis on the pathophysiology of sepsis and its treatment. DATA SOURCES: Published articles reporting studies on sepsis and septic shock or assessing the influence of genetics and pharmacogenomics in the treatment of critical illnesses. DATA ANALYSIS: Because most common diseases including sepsis have been shown to be influenced by inherited differences in our genes, completion of the Human Genome Project and the concomitant publication of the human single nucleotide polymorphism map both contribute to change our approach to medicine. Advances in genotyping techniques and bioinformatics enabling detection of single nucleotide polymorphisms have caused an explosion in pharmacogenomics-the research dealing with the interactions of an individual's genotype and the outcome of a drug therapy. Pharmacogenomics will undoubtedly be used to improve future health care and clinical research in different ways. Whereas treatment allocation has been based mainly on phenotype, genetic characterization will help researchers to identify suitable subjects for clinical trials, to facilitate interpretation of the results of clinical trials, and to identify novel targets for future drugs or new markets for current products. As interindividual variability in drug response is a substantial clinical problem, the second major objective of pharmacogenomic research is to decrease adverse responses to therapy through determination of adequate therapeutic targets and genetic polymorphisms that alter drug specificity and toxicity. Ultimately, genetic information will be used to select the most effective therapeutic agent and the optimal dosage to elicit the expected drug response for a given individual. Implementation of genetic criteria for stratification of patient populations and individual assessment of treatment risks and benefits emerges as a major challenge to the pharmaceutical industry. CONCLUSIONS: In the future, technologies such as gene chip array will enhance genetic medicine and provide novel insights into a patient's susceptibility to disease, enabling a better assessment of prognostic risk factors, quicker diagnosis, and accurate prediction of individual responsiveness to drugs. The predictable consequences of such an approach on the prevention and treatment of diseases could revolutionize medicine.

Animals↗

PubMed2004

The S447X polymorphism of the lipoprotein lipase gene is associated with lipoprotein lipid and blood pressure levels in Chinese patients with essential hypertension.

OBJECTIVE: To investigate the association between the S447X polymorphism of the lipoprotein lipase (LPL) gene and lipoprotein lipid and blood pressure (BP) levels in 904 Chinese subjects with essential hypertension. METHOD: Five hundred and sixty-three male and 341 female patients (aged 35-69 years) were randomly selected from hypertensive patients diagnosed in the Community-based Comprehensive Studies on Prevention and Control of Hypertension Project in China (CCPACH) and not treated with antihypertensive medications for at least 2 weeks immediately before blood collection. RESULTS: After multivariate adjustment for age, body mass index (BMI), smoking status, alcohol intake and serum glucose, the X447 allele was significantly associated with low triglyceride, log triglyceride : high-density lipoprotein (HDL)-cholesterol ratio and high HDL-cholesterol levels compared with the S447S genotype, but not with BP levels in the whole study population. However, upon stratification for dyslipidemic status, the X447 allele was associated with higher systolic blood pressure (SBP) (P < 0.05) and pulse pressure (PP) (P < 0.05) compared with the S447S genotype after multivariate adjustment in dyslipidemic subjects, but not in those without dyslipidemia. A statistically significant interaction between the LPL S447X polymorphism and dyslipidemic status was observed for SBP and PP levels, suggesting that dyslipidemic status might modify the effect of the LPL S447X polymorphism on BP levels. CONCLUSIONS: Our findings suggest that a high concentration of triglyceride and/or low concentration of HDL-cholesterol are associated with high SBP and PP in hypertensive patients with the X447 allele of the LPL gene.

Adult↗