Aortic valve sclerosis is associated with preclinical cardiovascular disease in hypertensive adults: the Hypertension Genetic Epidemiology Network study.

Rationale: Aortic valve sclerosis (AVS) has been associated with atherosclerosis and increased all-cause and cardiovascular death. However, whether AVS is associated with preclinical cardiovascular disease among adults at high risk because of hypertension has not been determined in a population-based sample.

Methods And Results: Clinical and echocardiographic parameters were measured in 1624 hypertensive participants (54 +/- 11 years, 65% women, 63% black, 17% diabetic, 19% smokers) without significant valvular or cardiovascular diseases in the population-based Hypertension Genetic Epidemiology Network study.

Effect of losartan versus atenolol on aortic valve sclerosis (a LIFE substudy).

Neither losartan- nor atenolol-based antihypertensive regimens could prevent the progression of aortic valve (AV) sclerosis in elderly, high-risk hypertensive patients, and the regression of AV sclerosis did not translate into reduced cardiovascular risk.

Association of inappropriate left ventricular mass with systolic and diastolic dysfunction: the HyperGEN study.

Background: Left ventricular mass (LVM) exceeding values appropriate for individual workload is associated with concentric LV geometry and systolic dysfunction at both the midwall and chamber levels, even independently of clearcut LV hypertrophy, and is a marker of adverse prognosis. No information is available on whether inappropriate LVM is associated with alterations of LV diastolic properties in unselected population-based studies.

Methods: We examined 1513 hypertensive participants from the HyperGEN population who were without prevalent cardiovascular disease.

Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in high-risk clinical and ethnic groups with diabetes.

Background: Diabetes causes 45% of incident end-stage renal disease (ESRD). Risk of progression is higher in those with clinical risk factors (albuminuria and hypertension), and in ethnic minorities (including blacks, Asians, and Latinos). Angiotensin-converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) slow the progression of diabetic nephropathy, yet little is known about their use among patients at high risk for progression to ESRD.

ATM, a DNA damage-inducible kinase, contributes to activation by high NaCl of the transcription factor TonEBP/OREBP.

High NaCl activates the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein (TonEBP/OREBP), resulting in increased transcription of several protective genes, including the glycine betaine/gamma-aminobutyric acid transporter (BGT1). High NaCl damages DNA, and DNA damage activates ataxia telangiectasia mutated (ATM) kinase through autophosphorylation on Ser-1981. TonEBP/OREBP contains ATM consensus phosphorylation sites at Ser-1197, Ser-1247, and Ser-1367.

Differences in left ventricular structure between black and white hypertensive adults: the Hypertension Genetic Epidemiology Network study.

The degree to which ethnic differences in left ventricular structure among hypertensive adults are independent of clinical and hemodynamic factors remains uncertain. We assessed whether left ventricular mass and geometry differ between black and white hypertensives after accounting for differences in such factors. Our study group comprised 1060 black and 580 white hypertensive participants free of valvular or coronary disease in a population-based cohort.

Missed appointments and poor glycemic control: an opportunity to identify high-risk diabetic patients.

Objective: When patients miss scheduled medical appointments, continuity and effectiveness of healthcare delivery is reduced, appropriate monitoring of health status lapses, and the cost of health services increases. We evaluated the relationship between missed appointments and glycemic control (glycosylated hemoglobin or HbA1c) in a large, managed care population of diabetic patients.

Research Design And Methods: Missed appointment rate was related cross-sectionally to glycemic control among 84,040 members of the Kaiser Permanente Northern California Diabetes Registry during 2000.

Comparison of cardiac structure and function in American Indians with and without the metabolic syndrome (the Strong Heart Study).

The metabolic syndrome (MS) is linked to cardiovascular risk. Recently, the Adult Treatment Panel (ATP) III provided new criteria for the definition of the MS. We analyzed the impact of the MS on cardiac structure and function and the independent association of the 5 different components of the ATP III-defined MS with cardiac markers of preclinical disease.

Relation of left ventricular hypertrophy to inflammation and albuminuria in adults with type 2 diabetes: the strong heart study.

Objective: To evaluate in adults with type 2 diabetes the extent to which the relation of left ventricular hypertrophy (LVH) to markers of systemic inflammation (fibrinogen and high-sensitivity C-reactive protein [hsCRP]) are affected by microangiopathy.

Research Design And Methods: We selected adults with type 2 diabetes using American Diabetes Association criteria from a population-based cohort, excluding those with medical history or electrocardiographic evidence of coronary heart disease or dialysis-dependent renal failure. LVH was assessed by echocardiogram.

Prognostic implications of ejection fraction from linear echocardiographic dimensions: the Strong Heart Study.

Background: Although echocardiography is commonly used to assess left ventricular (LV) systolic function, few data are available concerning the prognostic significance of LV ejection fraction (EF) calculated from linear echocardiographic measurements or 2-dimensional (2-D) wall motion scores in population-based samples.

Methods: Echocardiography was used in the second Strong Heart Study (SHS) examination to calculate LV EF in 2948 American Indians without prevalent coronary heart disease; 2923 had 2-D wall motion scores.

Results: Mildly and severely reduced LV EF occurred in 10% and 2% of participants, was associated with older age, male sex, higher systolic pressure, heart rate and markers of renal disease and inflammation.

Use of antibiotics is not associated with decreased risk of myocardial infarction among patients with diabetes.

Objective: To study the relationship between exposure to antibiotic treatment and risk of subsequent myocardial infarction (MI) in patients with diabetes.

Research Design And Methods: A case-control design was used to assess the effect of previous antibiotic exposure in diabetes patients with acute, nonfatal or fatal MI (case subjects) and individually matched control subjects (four control subjects to one case subject, matched on sex, age, and index date). Subjects were sampled from the Northern California Kaiser Permanente Diabetes Registry, a well-characterized, ethnically diverse diabetic population from Kaiser Permanente Medical Care Program, Northern California Region.

Association of albuminuria with systolic and diastolic left ventricular dysfunction in type 2 diabetes: the Strong Heart Study.

Objectives: We sought to compare systolic and diastolic function in American Indians with diabetes mellitus (DM) based on albuminuria status.

Background: Albuminuria has been shown to predict cardiovascular disease (CVD) in populations with DM. However, the mechanism of the association of albuminuria and CVD is unclear.

An appraisal of echocardiography as an epidemiological tool. The Strong Heart Study.

Purpose: Despite the prognostic importance of left ventricular (LV) mass (LVM) by M-mode echocardiography, concern exists about bias introduced by missing data. The American Society of Echocardiography has made recommendations for linear measurements of LV wall thickness and internal dimension used to calculate LVM, but it is unknown whether their substitution for suboptimal M-modes improves measurement yield and reduces bias.

Methods: LVM measurement yield and associations of missing data with risk factors were assessed in 3487 American Indian participants in Strong Heart Study (SHS) Phase II and compared to data from other large-scale studies.

Regulation of the NK-1 receptor gene expression in human macrophage cells via an NF-kappa B site on its promoter.

We report here that human monocytic/macrophage THP-1 cells express the neurokinin 1 receptor (NK-1R), and that exposure of these cells to the proinflammatory cytokine IL-1 beta increased the expression of the NK-1R gene at the mRNA and protein levels. Because IL-1 beta function involves nuclear factor kappa B (NF-kappa B) activation, these data suggest that this increase in the expression of the NK-1R gene is mediated by the NF-kappa B transcription factor. An earlier report noted that the promoter region of the human NK-1R gene contains a putative binding site for NF-kappa B [Takahashi, K.

Corticotropin-releasing hormone antagonists possess anti-inflammatory effects in the mouse ileum.

Background & Aims: Corticotropin-releasing hormone (CRH) released at local sites of inflammation promotes inflammation in the periphery. We investigated its effects in the intestinal responses caused by toxin A from Clostridium difficile, the causative agent of antibiotic-associated colitis.

Methods: Ileal loops were injected with 10 microg of toxin A, and enterotoxic responses were measured at various time points.

Progressive hypertrophy regression with sustained pressure reduction in hypertension: the Losartan Intervention For Endpoint Reduction study.

Objective: To examine the time course of left ventricular (LV) geometric response to blood pressure (BP) control during 2 years of systematic antihypertensive treatment.

Design: A total of 754 hypertensive patients with left ventricular hypertrophy (LVH) by Cornell voltage-duration product or Sokolow-Lyon voltage criteria on a screening electrocardiogram had their LV mass measured by echocardiogram at enrolment in the Losartan Intervention For Endpoint Reduction (LIFE) trial, and after 12 and 24 months of blinded therapy with losartan-based or atenolol-based regimens.

Setting: The LIFE trial, in which hypertensive patients with electrocardiographic LVH (Cornell voltage-duration product > 2440 mm x ms and/or Sokolow-Lyon voltage criteria SV1 + RV5-6 > 38 mm) were randomized to >or= 4 years double-blinded treatment with losartan or atenolol.

Appetite suppressants and valvular heart disease in a population-based sample: the HyperGEN study.

Purpose: Previous studies of the association between the use of appetite suppressants and valvular heart disease have not accounted for the effects of valvular structure and aortic root diameter, which are associated with obesity. We assessed whether the use of the appetite suppressants fenfluramine/dexfenfluramine, either alone or with phentermine, was associated with aortic regurgitation while adjusting for these variables.

Subjects And Methods: The sample included 2524 adult participants in the population-based Hypertension Genetic Epidemiology Network study.

Ethnic disparities in diabetic complications in an insured population.

Context: Higher rates of microvascular complications have been reported for minorities. Disparate access to quality health care is a common explanation for ethnic disparities in diabetic complication rates in the US population. Examining an ethnically diverse population with uniform health care coverage may be useful.

Mitral ratio of peak early to late diastolic filling velocity as a predictor of mortality in middle-aged and elderly adults: the Strong Heart Study.

Background: With aging, left ventricular filling tends to decrease in early diastole, reducing the mitral ratio of peak early to late diastolic filling velocity (E/A). However, the prognostic significance of low or high E/A in older adults remains to be elucidated in population-based samples.

Methods And Results: Doppler echocardiograms were analyzed in 3008 American Indian participants in the second Strong Heart Study examination who had no more than mild mitral or aortic regurgitation.

Gender difference in diastolic function in hypertension (the HyperGEN study).

Although several studies indicate that there are gender differences in left ventricular (LV) systolic function, it remains unclear whether similar differences exist with regard to diastolic function. Accordingly, Doppler echocardiograms were analyzed in 515 male and 839 female, mostly treated (95%) hypertensive participants enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) study with no evidence of abnormal wall motion or significant valvular heart disease. There was no difference in age between genders, but after adjusting for age and race, men had lower body mass indexes (29.

Clostridium difficile toxin A triggers human colonocyte IL-8 release via mitochondrial oxygen radical generation.

Background & Aims: Clostridium difficile toxin A causes mitochondrial dysfunction resulting in generation of oxygen radicals and adenosine triphosphate (ATP) depletion. We investigated whether mitochondrial dysfunction is involved in nuclear factor kappaB (NF-kappaB) activation and interleukin (IL)-8 release from toxin A-exposed enterocytes.

Methods: NF-kappaB activation and IL-8 release in response to toxin A were correlated with reactive oxygen intermediate (ROI) generation and ATP production in HT-29 monolayers or HT-29 cells exposed to ethidium bromide (EB) to inhibit mitochondrial function.

Gamma-tocopheryl quinone stimulates apoptosis in drug-sensitive and multidrug-resistant cancer cells.

Chemotherapy-induced cell death is linked to apoptosis, and there is increasing evidence that multidrug-resistance in cancer cells may be the result of a decrease in the ability of a cell to initiate apoptosis in response to cytotoxic agents. In previous studies, we synthesized two classes of electrophilic tocopheryl quinones (TQ), nonarylating alpha-TQ and arylating gamma- and delta-TQ, and found that gamma- and delta-TQ, but not alpha-TQ, were highly cytotoxic in human acute lymphoblastic leukemia cells (CEM) and multidrug-resistant (MDR) CEM/VLB100. We have now extended these studies on tumor biology with CEM, HL60 and MDR HL60/MX2 human promyelocytic leukemia, U937 human monocytic leukemia, and ZR-75-1 breast adenocarcinoma cells.