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Biomedical subjects

Margaret M Redfield

Publications and source records attributed to Margaret M Redfield.

At least 19 recordsLinked to original sources
PubMed2007

Unexplained pulmonary hypertension in elderly patients.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) preferentially affects young women. However, a subset of patients with IPAH is elderly. Our objective was to compare elderly (age >/= 65 years) vs younger persons with unexplained pulmonary hypertension (PH) and a presumptive diagnosis of IPAH. METHODS: Clinical, echocardiographic, hemodynamic, and survival data were collected on consecutive patients with suspected IPAH after evaluation in a large tertiary center PH clinic. RESULTS: Of 197 patients (mean age +/- SD, 52 +/- 16 years; 80% female), 48 patients (24%) were elderly. Elderly and younger patients had similar symptom severity, systolic pulmonary artery (PA) pressure (82.7 +/- 20.3 mm Hg vs 86.9 +/- 18.8 mm Hg, respectively; p = 0.21), and severity of right ventricular enlargement and dysfunction. Elderly patients had higher pulmonary capillary wedge pressure (PCWP) [15.3 +/- 7.3 mm Hg vs 11.1 +/- 5.3 mm Hg; p < 0.0001] and more frequently failed (56%) to meet hemodynamic criteria for IPAH (PH with PCWP < 15 mm Hg) than did younger patients (19%). Elderly patients also had higher systemic systolic (p < 0.0001) and pulse (p < 0.0001) pressures and more cardiovascular disease. Among those patients with normal PCWP, elderly patients had worse survival than young patients (p = 0.007). Among those patients with elevated PCWP, elderly patients had lower PA pressures (p = 0.04) and better survival (p = 0.02). CONCLUSIONS: Elderly patients with clinically suspected IPAH often fail to meet hemodynamic criteria for IPAH due to elevated PCWP. Studies to define the proper diagnostic strategy and the safety and efficacy of pulmonary vasodilators in elderly patients with unexplained PH are needed.

Age Factors↗
PubMed2006

Systolic and diastolic heart failure in the community.

CONTEXT: The heart failure (HF) syndrome is heterogeneous. While it can be defined by ejection fraction (EF) and diastolic function, data on the characteristics of HF in the community are scarce, as most studies are retrospective, hospital-based, and rely on clinically indicated tests. Further, diastolic function is seldom systematically assessed based on standardized techniques. OBJECTIVE: To prospectively measure EF, diastolic function, and brain natriuretic peptide (BNP) in community residents with HF. MAIN OUTCOME MEASURES: Echocardiographic measures of EF and diastolic function, measurement of blood levels of BNP, and 6-month mortality. DESIGN, SETTING, AND PARTICIPANTS: Olmsted County residents with incident or prevalent HF (inpatients or outpatients) between September 10, 2003, and October 27, 2005, were prospectively recruited to undergo assessment of EF and diastolic function by echocardiography and measurement of BNP. RESULTS: A total of 556 study participants underwent echocardiography at HF diagnosis. Preserved EF (> or =50%) was present in 308 (55%) and was associated with older age, female sex, and no history of myocardial infarction (all P<.001). Isolated diastolic dysfunction (diastolic dysfunction with preserved EF) was present in 242 (44%) patients. For patients with reduced EF, moderate or severe diastolic dysfunction was more common than when EF was preserved (odds ratio, 1.67; 95% confidence interval [CI], 1.11-2.51; P = .01). Both low EF and diastolic dysfunction were independently related to higher levels of BNP. At 6 months, mortality was 16% for both preserved and reduced EF (age- and sex-adjusted hazard ratio, 0.85; 95% CI, 0.61-1.19; P = .33 for preserved vs reduced EF). CONCLUSIONS: In the community, more than half of patients with HF have preserved EF, and isolated diastolic dysfunction is present in more than 40% of cases. Ejection fraction and diastolic dysfunction are independently related to higher levels of BNP. Heart failure with preserved EF is associated with a high mortality rate, comparable to that of patients with reduced EF.

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PubMed2006

Trends in prevalence and outcome of heart failure with preserved ejection fraction.

BACKGROUND: The prevalence of heart failure with preserved ejection fraction may be changing as a result of changes in population demographics and in the prevalence and treatment of risk factors for heart failure. Changes in the prevalence of heart failure with preserved ejection fraction may contribute to changes in the natural history of heart failure. We performed a study to define secular trends in the prevalence of heart failure with preserved ejection fraction among patients at a single institution over a 15-year period. METHODS: We studied all consecutive patients hospitalized with decompensated heart failure at Mayo Clinic Hospitals in Olmsted County, Minnesota, from 1987 through 2001. We classified patients as having either preserved or reduced ejection fraction. The patients were also classified as community patients (Olmsted County residents) or referral patients. Secular trends in the type of heart failure, associated cardiovascular disease, and survival were defined. RESULTS: A total of 6076 patients with heart failure were discharged over the 15-year period; data on ejection fraction were available for 4596 of these patients (76 percent). Of these, 53 percent had a reduced ejection fraction and 47 percent had a preserved ejection fraction. The proportion of patients with the diagnosis of heart failure with preserved ejection fraction increased over time and was significantly higher among community patients than among referral patients (55 percent vs. 45 percent). The prevalence rates of hypertension, atrial fibrillation, and diabetes among patients with heart failure increased significantly over time. Survival was slightly better among patients with preserved ejection fraction (adjusted hazard ratio for death, 0.96; P=0.01). Survival improved over time for those with reduced ejection fraction but not for those with preserved ejection fraction. CONCLUSIONS: The prevalence of heart failure with preserved ejection fraction increased over a 15-year period, while the rate of death from this disorder remained unchanged. These trends underscore the importance of this growing public health problem.

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PubMed2006

Membrane guanylyl cyclase receptors: an update.

Recent studies have demonstrated key roles for several membrane guanylyl cyclase receptors in the regulation of cell hyperplasia, hypertrophy, migration and extracellular matrix production, all of which having an impact on clinically relevant diseases, including tissue remodeling after injury. Additionally, cell differentiation, and even tumor progression, can be profoundly influenced by one or more of these receptors. Some of these receptors also mediate important communication between the heart and intestine, and the kidney to regulate blood volume and Na+ balance.

Animals↗
PubMed2006

Association of obesity with left ventricular remodeling and diastolic dysfunction in patients without coronary artery disease.

Obese patients frequently complain of dyspnea. Deconditioning and altered left ventricular (LV) systolic or diastolic function with elevated filling pressures may contribute to dyspnea. This study analyzed 4,281 patients who underwent diagnostic coronary angiography from January 1, 1995, to December 31, 2000. No patients had coronary artery stenoses >50% of the luminal diameter, and all underwent echocardiography within the same 6-year period. The association between body mass index (BMI) and LV structure and systolic and diastolic function was examined. All analyses controlled for age and gender, with the effect size for BMI expressed using a standardized coefficient (SC). A higher BMI was associated with greater LV mass (SC 0.18, p <0.001), wall thickness (SC 0.17, p <0.001), and end-diastolic diameter (SC 0.07, p <0.001). Stroke volume increased with a higher BMI (SC 0.12, p = 0.001), but there was no association between BMI and the ejection fraction (SC 0.003, p = 0.81). Hemodynamic data from invasive studies showed an association between a higher BMI and increased LV end-diastolic pressure (mean 17 mm Hg for BMI <25 kg/m(2) vs 24 mm Hg for BMI >or=40 kg/m(2); SC 0.18, p <0.001), which persisted after controlling for end-diastolic volume (SC 0.22, p <0.001). Obesity was associated with ventricular remodeling, which may normalize wall stress while increasing stroke volume to match metabolic demand. Obesity was not associated with decreased systolic function. However, obesity was associated with increased LV end-diastolic pressure, which suggests an association between obesity and diastolic dysfunction. In conclusion, ventricular remodeling, LV diastolic dysfunction, and elevated filling pressures may contribute to the prevalence of heart failure in obese patients.

Blood Pressure↗
PubMed2006

Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide: biomarkers for mortality in a large community-based cohort free of heart failure.

Recent studies report that, in the absence of heart failure and renal failure, plasma B-type natriuretic peptide (BNP) has prognostic value for mortality. We sought to confirm and extend these previous studies to assess BNP, measured by 3 distinct assays, as a biomarker for mortality in a strategy to enhance efforts at primary prevention and to better understand the clinical phenotype of such subjects at risk. We used a community-based cohort of 2042 subjects from Olmsted County, Minn, and individuals with heart or renal failure were excluded. BNP was assessed using 3 assays including Biosite and Shionogi for mature, biologically active BNP and the Roche assay for apparently nonbiologically active amino-terminal pro-BNP (NT-proBNP). Thorough echocardiographic and clinical data were recorded for all of the participants. Median follow-up for mortality was 5.6 years. BNP by all 3 of the assays was predictive of mortality. NT-proBNP and Biosite assays remained significant even after adjustment for traditional clinical risk factors and echocardiographic abnormalities including left ventricular hypertrophy and diastolic dysfunction. Echocardiography documented widespread structural changes in those with increasing BNP levels yet below levels observed in heart failure. We report in a large, well-characterized community-based cohort, free of heart failure, the first study to compare 3 distinct BNP assays as biomarkers for mortality in the same cohort. Our findings confirm the potential use of NT-proBNP and BNP biomarkers for future events and underscore that these peptides may also serve as biomarkers for underlying cardiac remodeling secondary to diverse cardiovascular disease entities.

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PubMed2006

Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction.

OBJECTIVES: This study sought to characterize factors influencing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and to evaluate the ability of NT-proBNP to detect left ventricular (LV) dysfunction in a large community sample. BACKGROUND: Secretion of BNP increases in cardiac disease, making BNP an attractive biomarker. Amino-terminal proBNP, a fragment of the BNP prohormone, is a new biomarker. We evaluated factors influencing NT-proBNP in normal patients and compared the ability of NT-proBNP and BNP to detect LV dysfunction in a large community sample. METHODS: Amino-terminal pro-BNP was determined in plasma samples of a previously reported and clinically and echocardiographically characterized random sample (n = 1,869, age > or =45 years) of Olmsted County, Minnesota. RESULTS: In normal patients (n = 746), female gender and older age were the strongest independent predictors of higher NT-proBNP. Test characteristics for detecting an LV ejection fraction < or =40% or < or =50% were determined in the total sample with receiver operating characteristic curves. Amino-terminal pro-BNP had significantly higher areas under the curve for detecting an LV ejection fraction < or =40% or < or =50% than BNP in the total population and in several male and age subgroups, whereas areas were equivalent in female subgroups. Age- and gender-adjusted cutpoints improved test characteristics of NT-proBNP. Both assays detected patients with systolic and/or moderate to severe diastolic dysfunction to a similar degree, which was less robust than the detection of LV systolic dysfunction alone. CONCLUSIONS: Amino-terminal pro-BNP in normal patients is affected primarily by gender and age, which should be considered when interpreting values. Importantly, in the entire population sample NT-proBNP performed at least equivalently to BNP in detecting LV dysfunction and was superior in some subgroups in detecting LV systolic dysfunction.

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PubMed2006

BNP-induced activation of cGMP in human cardiac fibroblasts: interactions with fibronectin and natriuretic peptide receptors.

Cardiac remodeling involves the accumulation of extracellular matrix (ECM) proteins including fibronectin (FN). FN contains RGD motifs that bind integrins at DDX sequences allowing signaling from the ECM to the nucleus. We noted that the natriuretic peptide receptor A (NPR-A) sequence contains both RGD and DDX sequences. The goal of the current investigation was to determine potential interactions between FN and NPR-A on BNP induction of cGMP in cultured human cardiac fibroblasts (CFs). Further, we sought to determine whether a Mayo designed NPR-A specific RGD peptide could modify this interaction. Here we reconfirm the presence of all three natriuretic peptide receptors (NPR) in CFs. CFs plated on FN demonstrated a pronounced increase in cGMP production to BNP compared to non-coated plates. This production was also enhanced by the NPR-A specific RGD peptide, which further augmented FN associated cGMP production. Addition of HS-142-1, a NPR-A/B antagonist, abrogated the responses of BNP to both FN and the NPR-A specific RGD peptide. Finally, we defined a possible role for the NPR-C through non-cGMP mechanisms in mediating the anti-proliferative actions of BNP in CFs where the NPR-C antagonist cANF 4-28 but not HS-142-1 blocked BNP-mediated inhibition of proliferation of CFs. We conclude that NPR-A interacts with components of the ECM such as FN to enhance BNP activation of cGMP and that a small NPR-A specific RGD peptide augments this action of BNP with possible therapeutic implications. Lastly, the NPR-C may also have a role in mediating anti-proliferative actions of BNP in CFs.

Cell Proliferation↗
PubMed2006

Unrecognized myocardial infarction: the association with cardiopulmonary symptoms and mortality is mediated via echocardiographic abnormalities of global dysfunction instead of regional dysfunction: the Olmsted County Heart Function Study.

BACKGROUND: There are very few data describing the association of electrocardiogram-based unrecognized myocardial infarction (ECG-UMI) with nonanginal cardiopulmonary symptoms, echocardiographic abnormalities, and mortality in the community. METHODS: We studied 2042 Olmsted County residents, who were randomly selected and aged > or = 45 years, by a survey questionnaire for symptoms, echocardiogram for structural abnormalities, and a 5-year follow-up for all-cause mortality. Unrecognized myocardial infarctions (n = 81) were diagnosed if ECG-based myocardial infarction (MI) criteria were met without the history of a documented recognized MI. RESULTS: In UMI versus no MI controls, the prevalence (%) of dyspnea on exertion (49 vs 29), orthopnea (6 vs 4), palpitations (20 vs 15), and history of fluid overload (6 vs 1) was significantly higher (P < .05). The associations of exertional dyspnea and history of fluid overload with UMI were independent of age, sex, and pulmonary disease but had a significant reduction in their magnitude after adjusting for global dysfunction (diastolic or systolic dysfunction). All the 4 symptoms were associated with increased risk of mortality (hazard ratios ranging from 2.3 to 9.1, P < .0001), which was meaningfully attenuated by adjusting for ECG-UMI status. Global ventricular dysfunction had a more significant impact on this association than regional ventricular dysfunction (wall motion abnormalities). CONCLUSIONS: The increased risk of mortality associated with symptoms is at least in part mediated via ECG-UMI. Structural abnormalities of global dysfunction play a greater role in mediating this risk than regional dysfunction, challenging the current clinical practice of calling an ECG-based MI false positive in symptomatic adults in the absence of wall motion abnormalities.

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PubMed2006

Diabetes in heart failure: prevalence and impact on outcome in the population.

PURPOSE: Little is known on the prevalence and prognostic importance of diabetes mellitus (DM) among individuals with heart failure (HF) in community-based cohorts. METHODS: Within Olmsted County, Minnesota, a random sample of all subjects with a first diagnosis of HF between 1979 and 1999 was validated using Framingham criteria. DM was validated using glycemic criteria. RESULTS: Among 665 subjects with HF (mean age 77+/-12 years, 46% male), 20% had prior DM. Subjects with DM were younger, had greater body mass index (BMI), and lower left ventricular ejection fraction than subjects without diabetes. The prevalence of DM increased markedly over time (3.8% per year; 95% confidence interval [CI], 0.8 to 6.9; P=.024), independently of BMI, particularly in older subjects (odds ratio of having DM in 1999 compared with 1979 was 3.93 [95% CI, 1.57 to 9.83] in subjects > or = 75 years vs. 1.11 [95% CI, .40 to 3.05] in subjects <75 years). Five-year survival was 37% among subjects with DM versus 46% among subjects without (P=.017). The risk of death associated with DM differed markedly according to clinical coronary artery disease (CAD) (P=.025). Subjects with DM and no CAD had a higher risk of death (relative risk [RR]=1.79 [95% CI, 1.33 to 2.41]) than those with CAD (RR=1.11 [95% CI, .81 to 1.51]), independently of age, sex, BMI, renal function, calendar year of HF, comorbidity and EF. CONCLUSIONS: Among community-dwelling patients with HF, the prevalence of DM increased markedly over time. DM is associated with a large increase in mortality, particularly among subjects without clinical CAD, underscoring the importance of aggressive management of DM in HF.

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PubMed2006

Secular trends in renal dysfunction and outcomes in hospitalized heart failure patients.

BACKGROUND: Renal dysfunction and worsening renal function (WRF) during heart failure (HF) therapy predict outcomes. We determined whether the severity of renal dysfunction, the incidence of WRF or outcomes have changed over time (secular trends) in patients hospitalized for HF therapy. METHODS AND RESULTS: A total of 6440 consecutive unique patients admitted for HF to Mayo Clinic Hospitals Rochester, MN, January 1, 1987, to December 31, 2002, were identified and data extracted from electronic databases. Over the study period, age and admission creatinine increased, whereas estimated glomerular filtration rate and hemoglobin decreased (P < .0001 for all). The prevalence of hypertension and diabetes among HF patients also increased over time (P < .0001). The incidence of WRF was stable. Renal dysfunction and development of WRF were associated with mortality. When adjusted for the changes in baseline characteristics of HF patients, mortality declined over the study period. CONCLUSION: Hospitalized HF patients are increasingly elderly, have a greater prevalence of diseases that lead to renal dysfunction, and have more severe renal dysfunction and anemia on admission. However, adjusting for these secular trends in patient characteristics, mortality after HF admission is improving. These data enhance our understanding of the changing natural history of HF.

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PubMed2006

Use of a novel ultrafiltration device as a treatment strategy for diuretic resistant, refractory heart failure: initial clinical experience in a single center.

BACKGROUND: The System 100 UF device allows ultrafiltration (UF) via peripheral access and is approved for use in heart failure (HF), although clinical trials defining optimal target population and clinical utility are lacking. We report our initial experience with clinical use of this system in very advanced, diuretic resistant HF patients. METHODS AND RESULTS: Eleven HF patients (mean age 70 years) underwent 1 to 5 UF treatments each (total 32 UF). The goal was to remove 4 liters of fluid per 8-hour UF. Baseline creatinine averaged 2.2 mg/dL (range .9-3.2) while estimated glomerular filtration rates (GFRs) averaged 38 mL/min (range 20-87). Nine patients (82%) had moderate (GFR 30-59; n = 3) or severe (GFR <30; n = 6) renal dysfunction. Nine patients (82%) had documented right ventricular dysfunction, 6 with severe tricuspid regurgitation. Average daily intravenous furosemide dose prior to UF was 258 mg (range 80-480). Patients had received nesiritide (n = 4), dopamine (n = 4), and zaroxylyn (n = 7) prior to UF. Of the 32 UF treatments, 13 (41%) removed >3500 mL, 11 (34%) removed 2500-3500 mL, and 8 (25%) removed <2500 mL. Only one UF treatment (3%) was aborted due to hypotension. There were no significant complications related to UF. Five patients (45%) experienced an increase in creatinine of >.3 mg/dl. Five patients required dialysis for persistent diuretic resistant volume overload or uremic symptoms. Six-month mortality was 55%. CONCLUSIONS: Peripheral UF safely but variably removed fluid. In this very high-risk, advanced HF population, 45% of patients developed worsening renal function during UF therapy. Controlled studies are needed to determine the impact of UF on renal function and outcomes in high-risk populations such as this.

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PubMed2006

Use of ejection fraction tests and coronary angiography in patients with heart failure.

OBJECTIVE: To examine the use of tests that measure ejection fraction (EF) and the use of coronary angiography among patients with an initial diagnosis of heart failure (HF). PATIENTS AND METHODS: All potential cases of incident HF in Olmsted County, Minnesota, between 1979 and 1999 were identifled. In a random sample of cases validated with the Framingham criteria, we examined the frequency of tests that measure EF (echocardiography, radionuclide ventriculography, and left ventricular angiography) and coronary angiography within 90 days after diagnosis. RESULTS: A total of 655 patients with incident HF were included in the analysis. The use of tests that measure EF and coronary angiography increased early in the study period but stabilized thereafter. In the most recent years (1995-1999), EF was measured in 65% of the patients and coronary angiography performed in 12%. After adjustment for year of diagnosis, body mass index, hypertension, diabetes mellitus, smoking, hyperlipidemia, comorbidity, prior myocardial infarction, and prior angina, men were more likely than women to have EF measured (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.16) and coronary angiography (OR, 2.61; 95% CI, 1.43-4.76). Increasing age was associated with less use of tests (OR, 0.83; 95% CI, 0.76-0.91; for EF measurement; OR, 0.72; 95% CI, 0.63-0.82; for coronary angiography for every 5-year increase in age). CONCLUSION: Among patients with HF, tests that measure EF are used substantially less than recommended, and coronary angiograms are used infrequently. Use was particularly low in women and elderly patients. Given the potential benefits of such tests, including more appropriate therapy and more objective monitoring of ventricular function, outcomes in persons with HF may be improved with more consistent use.

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PubMed2005

Bioenergetic protection of failing atrial and ventricular myocardium by vasopeptidase inhibitor omapatrilat.

Deficient bioenergetic signaling contributes to myocardial dysfunction and electrical instability in both atrial and ventricular cardiac chambers. Yet, approaches capable to prevent metabolic distress are only partially established. Here, in a canine model of tachycardia-induced congestive heart failure, we compared atrial and ventricular bioenergetics and tested the efficacy of metabolic rescue with the vasopeptidase inhibitor omapatrilat. Despite intrinsic differences in energy metabolism, failing atria and ventricles demonstrated profound bioenergetic deficiency with reduced ATP and creatine phosphate levels and compromised adenylate kinase and creatine kinase catalysis. Depressed phosphotransfer enzyme activities correlated with reduced tissue ATP levels, whereas creatine phosphate inversely related with atrial and ventricular load. Chronic treatment with omapatrilat maintained myocardial ATP, the high-energy currency, and protected adenylate and creatine kinase phosphotransfer capacity. Omapatrilat-induced bioenergetic protection was associated with maintained atrial and ventricular structural integrity, albeit without full recovery of the creatine phosphate pool. Thus therapy with omapatrilat demonstrates the benefit in protecting phosphotransfer enzyme activities and in preventing impairment of atrial and ventricular bioenergetics in heart failure.

Animals↗
PubMed2005

Age- and gender-related ventricular-vascular stiffening: a community-based study.

BACKGROUND: Increases in vascular (Ea), ventricular systolic (Ees), and ventricular diastolic (Ed) elastance (stiffness) may contribute to the pathogenesis of heart failure (HF) with preserved ejection fraction (HFnlEF). The prevalence of HFnlEF increases strikingly with age, particularly in women. We hypothesized that ventricular-vascular stiffening may occur with age and be more pronounced in women in the general community. METHODS AND RESULTS: In a cross-sectional sample of Olmsted County, Minn, residents > or =45 years old (n=2042), clinical data, Doppler echocardiography, and blood pressure (BP) measurements were obtained. Ea was calculated from stroke volume and systolic BP and indexed to body size (EaI). Ees was calculated by a modified single-beat method using systolic and diastolic BP, stroke volume, ejection fraction, timing intervals, and an estimated normalized ventricular elastance at arterial end diastole. Operant Ed was calculated from Doppler indices reflective of atrial pressures and the diastolic filling volume. EaI, Ees, and Ed all increased with age in men and in women (P<0.0001 for all). Ees increased more steeply with age in women (P=0.002). Adjusted for age, EaI, Ees, and Ed were higher in women than in men (P<0.0001 for all). Findings were similar in those without known or suspected cardiovascular disease (n=623). CONCLUSIONS: In the community, advancing age and female gender are associated with increases in vascular and ventricular systolic and diastolic stiffness even in the absence of cardiovascular disease. We speculate that this combined ventricular-vascular stiffening may contribute to the increased prevalence of HFnlEF in elderly persons and particularly in elderly women.

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PubMed2005

Elevated blood pressure and cardiac hypertrophy after ablation of the gly96/IEX-1 gene.

gly96/IEX 1 is a growth- and apoptosis-regulating, immediate early gene that is widely expressed in epithelial and vascular tissues. In vascular tissues, expression of the gene is induced by mechanical stretch, and overexpression of the gene prevents injury-induced vascular smooth muscle hypertrophy and neointimal hyperplasia. We now show that deletion of the gly96/IEX-1 gene in mice is associated with development of elevated blood pressure, cardiac hypertrophy, and diminished fractional shortening of the left ventricle. Systolic blood pressure in conscious male gly96/IEX-1-/- mice is 20-25 mmHg higher than in gly96/IEX-1+/+ mice. Serum and/or urine concentrations of sodium, potassium, creatinine, angiotensin II, corticosterone, aldosterone, epinephrine, norepinephrine, prostaglandin E2, thromboxane B2, prostaglandin-6-keto-1alpha, nitrites and nitrates, cAMP, and cGMP are normal in gly96/IEX-1-/- mice. Alterations in dietary sodium intake do not alter blood pressure in gly96/IEX-1-/- mice. Aortic mRNAs for endothelial nitric oxide synthase, guanylate cyclase-alpha, and cGMP kinase-1 are increased in gly96/IEX-1-/- mice. Treatment with Nomega-nitro-L-arginine methyl ester or L-arginine does not alter blood pressure in gly96/IEX-1-/- mice. Gly96/IEX-1-/- mice respond to infused sodium nitroprusside with decrements in blood pressure similar to those seen in wild-type littermate mice. In contrast to gly96/IEX-1 transgenic mice that have abnormalities in immune function, gly96/IEX-1-/- mice have normal lymphoid tissue architecture and a normal complement of T and B cells in lymphoid tissues. Ablation of the gly96/IEX-1 gene results in hypertension and cardiac hypertrophy, suggesting a novel role for this gene in cardiovascular physiology.

Animals↗
PubMed2005

Echocardiographic characteristics of electrocardiographically unrecognized myocardial infarctions in a community population.

Unrecognized myocardial infarction (UMI) as diagnosed by surveillance electrocardiography has been shown to carry the same poor prognosis as recognized myocardial infarction (RMI). The echocardiographic characteristics of UMI have never been studied before. Due to a similar prognosis, we hypothesized that UMI and RMI would exhibit similar degrees of echocardiographic ventricular dysfunction. We studied a random community cohort of 2,042 adults who were > or =45 years of age in a cross-sectional setting in Olmsted County, Minnesota. RMI was diagnosed by review of medical records and UMI was diagnosed if the electrocardiogram met MI criteria without a previous MI recorded in the medical record. All subjects underwent transthoracic echocardiography. We identified 80 patients who had UMI and 101 who had RMI. In bivariate analyses, a stepwise increase in echocardiographic abnormalities was observed from participants who had no MI to UMI to RMI: respective mean ejection fractions were 63%, 61%, and 55; prevalences in left ventricular enlargement were 13%, 22%, and 52%; mean left ventricular mass indexes were 98, 103, and 118 g/m(2); prevalences in regional wall motion abnormality were 2%, 13%, and 42%; and prevalences in diastolic dysfunction were 25%, 56%, and 65% (p for trend <0.0001 for all comparisons). After adjusting for standard coronary risk factors, patients who had UMI continued to exhibit significant abnormalities in systolic dysfunction, diastolic dysfunction, and regional wall motion abnormality, although to a lesser extent than patients who had RMI. In conclusion, patients who have UMI manifest structural abnormalities more commonly than do patients who have no MI but less commonly than do those who have RMI. The similar prognosis after UMI and RMI cannot be explained by comparable degrees of ventricular damage.

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