Does cardiovascular phenotype explain the association between diabetes and incident heart failure? The Strong Heart Study.

BACKGROUND AND AIMS: Diabetes remains a predictor of incident heart failure (HF), independent of intercurrent myocardial infarction (MI) and concomitant risk factors. Initial cardiovascular (CV) characteristics, associated with incident heart failure (HF) might explain the association of diabetes with incident HF. METHODS AND RESULTS: Participants to the 2nd Strong Heart Study exam, without prevalent HF or coronary heart disease, or glomerular filtration rate <30 mL/min/1.73 m(2), were analyzed (n = 2757, 1777 women, 1278 diabetic). Cox regression of incident HF (follow-up 8.91 ± 2.76 years) included incident MI censored as a competing risk event. Acute MI occurred in 96 diabetic (7%) and 84 non-diabetic participants (6%, p = ns). HF occurred in 156 diabetic (12%) and in 68 non-diabetic participants (5%; OR = 2.89, p < 0.001). After accounting for competing MI and controlling for age, gender, BMI, systolic blood pressure, smoking habit, plasma cholesterol, antihypertensive treatment, heart rate, fibrinogen and C-reactive protein, incident HF was predicted by greater LV mass index, larger left atrium, lower systolic function, greater left atrial systolic force and urinary albumin/creatinine excretion. Risk of HF was reduced with more rapid LV relaxation and anti-hypertensive therapy. Diabetes increases hazard of HF by 66% (0.02 < p < 0.001). The effect of diabetes could be explained by the level of HbA1c. CONCLUSIONS: Incident HF occurs more frequently in diabetes, independent of intercurrent MI, abnormal LV geometry, subclinical systolic dysfunction and indicators of less rapid LV relaxation, and is influenced by poor metabolic control. Identification of CV phenotype at high-risk for HF in diabetes should be advised.

Metabolic syndrome and left ventricular hypertrophy in the prediction of cardiovascular events: the Strong Heart Study.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is associated with increased prevalence of echocardiographic LV hypertrophy (LVH), a potent predictor of cardiovascular (CV) outcome. Whether MetS increases risk of CV events independently of presence of LVH has never been investigated. It is also unclear whether LVH predicts CV risk both in the presence and absence of MetS. METHODS AND RESULTS: Participants in the 2nd Strong Heart Study examination without prevalent coronary heart disease, congestive heart failure or renal insufficiency (plasma creatinine >2.5mg/dL) were studied (n=2758; 1746 women). MetS was defined by WHO criteria. Echocardiographic LV hypertrophy was defined using population-specific cut-point value for LV mass index (>47.3g/m(2.7)). After controlling for age, sex, LDL-cholesterol, smoking, plasma creatinine, diabetes, hypertension and obesity, participants with MetS had greater probability of LVH than those without MetS (OR=1.55 [1.18-2.04], p<0.002). Adjusted hazard of composite fatal and non-fatal CV events was greater when LVH was present, in participants without (HR=2.03 [1.33-3.08]) or with MetS (HR=1.64 [1.31-2.04], both p<0.0001), with similar adjusted population attributable risk (12% and 14%). After adjustment for LVH, risk of incident CV events remained 1.47-fold greater in MetS (p<0.003), an effect, however, that was not confirmed when diabetic participants were excluded. CONCLUSION: LVH is a strong predictor of composite 8-year fatal and non-fatal CV events either in the presence or in the absence of MetS and accounts for a substantial portion of the high CV risk associated with MetS.

Accelerated atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus.

It is important for primary care physicians to recognise rheumatoid arthritis and systemic lupus erythematosus patients as high-risk groups for atherosclerosis, requiring aggressive risk-factor modification. Recent studies suggest that this increased risk is not explained by an excess of traditional risk factors, but rather appears to be related to underlying rheumatic disease activity. Moreover, there is emerging data that aggressive treatment with disease-modifying agents may reduce the incidence of atherosclerosis in these conditions.

Impact of age on left ventricular hypertrophy regression during antihypertensive treatment with losartan or atenolol (the LIFE study).

To assess the influence of age on changes in left ventricular (LV) mass and geometry during antihypertensive treatment, we related age to clinical and echocardiographic findings before and after 4 years of antihypertensive treatment in a subset of 560 hypertensive patients without known concurrent disease in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which randomized patients to blinded losartan- or atenolol-based treatment. Patients >/=65 years (older group) included more women and patients with isolated systolic hypertension or albuminuria (all P<0.05). Compared to patients <65 years, older patients had higher pulse pressure, LV mass, and prevalence of concentric hypertrophy at baseline (78 vs 69 mmHg, 234 vs 224 g, and 28 vs 16%, respectively, all P<0.01), while the mean blood pressure did not differ. Over 4 years, reductions in LV mass and the mean blood pressure were similar in both groups, but older patients more often had residual hypertrophy (31 vs 15%, P<0.001) with a preponderance of eccentric geometry. In multivariate analysis of 4-year change in LV mass controlling for baseline mass, larger hypertrophy reduction was associated with losartan treatment, while age, gender, body mass index, and 4-year change in pulse pressure and albuminuria did not enter (Multiple R (2)=0.40, P<0.001). Thus, in up-to-80-year-old hypertensive patients with left ventricular hypertrophy, age did not significantly attenuate hypertrophy reduction during antihypertensive treatment, although residual hypertrophy was more prevalent in older patients as a consequence of higher initial LV mass.

Usefulness of the assessment of the appropriateness of left ventricular mass to detect left ventricular systolic and diastolic abnormalities in absence of echocardiographic left ventricular hypertrophy: the LIFE study.

Conventional definitions of left ventricular (LV) hypertrophy do not account for interindividual differences in loading conditions. We may define LV mass as inappropriately high when exceeding 128% of theoretical values predicted by gender, height(2.7), and stroke work, which explain up to 82% of the variability of LV mass in normal reference subjects. In 652 participants in the Losartan Intervention For Endpoint reduction in hypertension study without clinically overt cardiovascular disease or diabetes, we investigated whether inappropriately high LV mass is associated with relevant LV abnormalities independent of traditional definition of LV hypertrophy (ie, LV mass index >116 g/m(2) in men and >104 g/m(2) in women). The study sample was divided into three groups: patients with inappropriately high LV mass but without LV hypertrophy were compared to patients with LV hypertrophy and to patients with appropriate LV mass and without LV hypertrophy. Patients with inappropriately high but nonhypertrophic LV mass had higher body mass index and relative wall thickness, and lower LV myocardial systolic function, than patients with appropriate LV mass or patients with LV hypertrophy. In multivariate analyses, inappropriately high LV mass was independently associated with lower myocardial systolic function independent of LV hypertrophy and other covariates. Inappropriately high LV mass was also associated with prolonged isovolumic relaxation time and lower mitral E/A ratio independent of covariates. In conclusion, inappropriately high LV mass was associated with relevant, often preclinical, manifestations of cardiac disease in the absence of traditionally defined echocardiographic LV hypertrophy and concentric geometry.

Relation of insulin resistance to markers of preclinical cardiovascular disease: the Strong Heart Study.

BACKGROUND AND AIMS: To investigate whether insulin-resistance influences echocardiographic markers of preclinical disease, independent of significant confounders. METHODS AND RESULTS: We examined 1,471 (59 +/- 8 years) non-diabetic individuals (WHO criteria) with available echocardiograms from the Strong Heart Study cohort. Among them, 530 subjects had arterial hypertension (62% on medications), 152 had impaired glucose tolerance (GT) and 460 were normotensive, non-obese with normal GT. Insulin resistance was estimated by the Homeostasis Model Assessment (HOMA). LV mass, systolic function measured at the endocardium and the midwall (also correcting for circumferential wall stress) and arterial compliance (stroke volume/pulse pressure as a percent of predicted from body weight, age and heart rate [delta %SV/PP]) were measured by echocardiography, as prognostically validated markers of preclinical disease. HOMA-index was related positively to body mass index (BMI), waist/hip ratio (WHR), blood pressure, left ventricular (LV) mass, and negatively to arterial compliance (all p < 0.005) in the whole population, as well as in separate normotensive or hypertensive groups. In multiple regression models, relation of HOMA-index with the markers of risk was adjusted for age, sex, WHR, body mass index, presence of hypertension and number of antihypertensive medications. In this analysis, neither LV mass nor indices of systolic function were independently related to HOMA-index. In contrast, HOMA-index maintained a significant negative association with delta %SV/PP, independent of demographics, hypertension, treatment and body fat distribution. Also, HOMA-index maintained an independent relation with LV mass, when WHR and BMI were not included in the regression model. CONCLUSIONS: After accounting for relevant biological covariates, including body mass and fat distribution, insulin-resistance measured by HOMA is not an independent correlate of LV mass and function, but negatively influences arterial compliance.

Enfermería basada en evidencias. Aportaciones y propuestas / Nursing based in evidences: contributions and proposals

Este texto recoge las conclusiones de la 1º Reunión sobre Enfermería Basada en la Evidencia (Granada, 29 de noviembre de 2002) una vez que ha sido sometido a consenso entre los participantes. Los temas de trabajo y los objetivos centrales de este foro fueron cuatro: evaluar la actividad realizada en España sobre la Enfermería Basada en la Evidencia, dar a conocer los distintos grupos que están trabajando sobre la evidencia en enfermería en España, proponer estrategias conjuntas de trabajo para el futuro y definir un marco de referencia para la enfermería española acorde con las líneas de desarrollo internacionales. Las recomendaciones y propuestas derivadas de la Reunión se han agrupado en cuatro grandes preguntas que remiten a cada uno de los objetivos planteados en la convocatoria: ¿Cuál es el marco de referencia de la evidencia científica en la Enfermería como disciplina?, ¿Qué es lo que se ha realizado en España sobre Enfermería Basada en la Evidencia?, ¿Cuáles son las líneas prioritarias de trabajo?, y ¿Qué aporta el concepto de evidencia científica a la práctica de los cuidados? (AU)

Cardiac and vascular remodeling in older adults with borderline isolated systolic hypertension: the ICARe Dicomano Study.

Although borderline isolated systolic hypertension (ISH), defined as a blood pressure of 140 to 159/<90 mm Hg, is a proven cardiovascular risk factor, the major clinical trials on treatment of ISH have used a cutoff of 160 mm Hg. Moreover, no data exist on the cardiovascular modifications associated with borderline ISH. Therefore, we compared subjects with borderline ISH to subjects with diastolic hypertension (diastolic blood pressure > or =90 mm Hg) or ISH. Community-dwelling residents (age > or =65 years) of a small town in Italy (Dicomano) underwent extensive clinical examination, echocardiography, carotid ultrasonography, and applanation tonometry. Only untreated subjects were included in this analysis: 95 with diastolic hypertension, 87 with borderline ISH, and 43 with ISH. Despite lower systolic and mean pressures in borderline ISH, left ventricular mass was similar to that in diastolic hypertension. In univariate and multivariate analysis, pulse pressure but not systolic pressure was related to left ventricular mass. Borderline ISH subjects had a tendency to greater carotid cross-sectional area and stiffness index than did diastolic hypertensive subjects despite lower mean carotid pressure, whereas the number of atherosclerotic plaques was similar in the 2 groups. Pulse pressure but not systolic pressure was independently related to carotid remodeling. In our community-based, older population, individuals with borderline ISH had a similar prevalence of left ventricular hypertrophy and carotid atherosclerosis as that of subjects with diastolic hypertension, despite lower systolic and mean pressures. Among blood pressure values, pulse pressure was the single or strongest independent predictor of cardiovascular remodeling.

Prevalence and correlates of mitral valve prolapse in a population-based sample of American Indians: the Strong Heart Study.

PURPOSE: Mitral valve prolapse is heritable and occurs frequently in the general population despite associations with mitral regurgitation and infective endocarditis, suggesting that selective advantages might be associated with mitral valve prolapse. SUBJECTS AND METHODS: Clinical examination and 2-dimensional and color Doppler echocardiography were performed in 3340 American Indian participants in the Strong Heart Study. RESULTS: Mitral valve prolapse (clear-cut billowing of one or both mitral leaflets across the mitral anular plane in 2-dimensional parasternal long-axis recordings or >2-mm late systolic posterior displacement of mitral leaflets by M mode) occurred in 37 (1.8%) of 2077 women and 20 (1.6%) of 1263 men (P = 0.88); 32 (3.5%) of 907 patients with normal glucose tolerance, 11 (2.3%) of 486 patients with impaired glucose tolerance, and 13 (0.7%) of 1735 patients with diabetes (P <0.0001). Participants with mitral valve prolapse had lower mean (+/- SD) body mass index (28 +/- 5 kg/m(2) vs. 31 +/- 6 kg/m(2), P = 0.001) and blood pressure (124/71 +/- 19/10 mm Hg vs. 130/75 +/- 21/10 mm Hg, P <0.05), as well as lower levels of fasting glucose, triglycerides, serum creatinine, and log urine albumin/creatinine ratio (all P <0.001), than did those without mitral valve prolapse, although all subjects were similar in age (60 +/- 8 years). Participants with mitral valve prolapse had lower ventricular septal (0.87 +/- 0.08 cm vs. 0.93 +/- 0.13 cm) and posterior wall thicknesses (0.82 +/- 0.08 cm vs. 0.87 +/- 0.10 cm), mass (38 +/- 7 g/m(2.7) vs. 42 +/- 11 g/m(2.7)), and relative wall thickness (0.33 +/- 0.04 vs. 0.35 +/- 0.05), and increased stress-corrected midwall shortening (all P <0.01). Mitral valve prolapse was associated with a higher prevalence of mild (16 of 57 [28%] vs. 614 of 3283 [19%]) and more severe mitral regurgitation (5 of 57 [9%] vs. 48 of 3283 [1%], P <0.0001). Regression analyses showed prolapse was associated with low ventricular relative wall thickness, high midwall function, and low urine albumin/creatinine ratio, independent of age, sex, body mass index, and diabetes. CONCLUSIONS: Mitral valve prolapse is fairly common and is strongly associated with mitral regurgitation in the general population. However, it is also associated with lower body weight, blood pressure, and prevalence of diabetes; a more favorable metabolic profile and ventricular geometry; and better myocardial and renal function.

Fibrinogen and preclinical echocardiographic target organ damage: the strong heart study.

Relations of fibrinogen to preclinical target organ damage, such as left ventricular hypertrophy, systolic dysfunction, and increased arterial stiffness while accounting for traditional risk factors, are unknown in a population-based sample free of clinically overt coronary heart disease. Therefore, we studied clinical and echocardiographic characteristics of 2709 American Indians participating in the Strong Heart Study without symptomatic atherosclerosis. The study sample was divided into tertiles of fibrinogen (cut-points, 3.24 and 3.83 g/L). Mean age, body mass index, proportion of women, and prevalences of hypertension and diabetes increased from the first to third tertile of fibrinogen. After adjustment for covariates, systolic and pulse pressures did not significantly differ among tertiles of fibrinogen, whereas diastolic pressure was slightly lower in the third than in lower tertiles of fibrinogen. HDL cholesterol was lower and plasma creatinine and urinary albumin/creatinine ratio was higher in the third tertile of fibrinogen. Left ventricular mass index, pulse pressure/stroke index, an estimate of arterial stiffness, and cardiac index were higher and left ventricular systolic function and total peripheral resistance were lower in the third than in two lower tertiles of fibrinogen independent of major covariates. In multiple regression analyses, left ventricular mass and pulse pressure/stroke index were positively associated with, and stress-corrected midwall shortening negatively associated with fibrinogen, independent of major covariates. Participants with fibrinogen >3.83 g/L were more likely to have at least 1 preclinical cardiovascular abnormality such as left ventricular hypertrophy, elevated arterial stiffness, or systolic myocardial dysfunction independent of covariates including renal dysfunction (adjusted odds ratio, 1.38; P<0.001). Thus, in a population sample of adults without clinically overt coronary heart disease, elevated fibrinogen is an independent correlate of prognostically relevant cardiovascular target organ damage.

Relation of heart rate to left ventricular dimensions in normotensive, normal-weight children, adolescents and adults.

BACKGROUND: The quantitative relation between body growth and changes in heart rate, and the relationship of heart rate to left ventricular (LV) dimensions, independent of the influence of body size, have been only marginally investigated. Accordingly, we designed this study to investigate the relation between heart rate, body size and LV dimensions in children, adolescents and adults over a broad age span. METHODS: Eight hundred and nineteen normotensive, multi-racial, normal-weight individuals (444 males, 375 females, aged 1-85 years) with normal LV systolic function were studied at echocardiography in three centers, using previously reported methods. The resting heart rate was measured on the M-mode echo-tracing or right after the echocardiogram with the subject still in the supine position. RESULTS: In children and adolescents (up to 17 years), the heart rate decreased with increasing body height (r = -0.51, p < 0.0001) and body weight (r = -0.42, p < 0.0001), in a similar manner in girls and boys. In adults, the heart rate was higher in women than in men, but it was not independently related to body size. The LV diastolic diameter was higher in males and decreased with increasing heart rate in children and adolescents (r = -0.45) as well as in adults (r = -0.25, both p < 0.0001). This relation was also independent of the effect of body size, sex and race. Similarly, the LV mass increased with decreasing heart rate in children and adolescents (r = -0.45), but the association was not confirmed after controlling for body size, sex and race. In adults, heart rate was inversely related to LV mass (r = -0.21, p < 0.0001), and this relation was also independent of body size, sex, race, age and blood pressure (p < 0.001). In women, the relation of heart rate to LV mass/height2.7 was less close than in men, due to the greater increase in LV mass with age. CONCLUSIONS: The heart rate has an inverse association with the LV chamber diameter and with the LV mass in children-adolescents and in adults. This relation is largely, but not uniquely, mediated by body proportions, especially during body growth.

Accelerated atherosclerosis in systemic lupus erythematosus: implications for patient management.

One of the most compelling clinical challenges in the management of systemic lupus erythematosus (SLE) is the high incidence of atherosclerotic cardiovascular disease (ASCVD). Potential mechanisms for accelerated atherosclerosis in SLE include chronic inflammation, excess of traditional risk factors, and corticosteroid therapy. Given the high prevalence of atherosclerosis in SLE patients relative to young women in the general population, we propose that the presence of SLE constitutes a sufficiently potent risk factor for ASCVD to warrant more aggressive goals for risk factor reduction and strategies to reduce inflammation.

Relation of blood pressure variability to carotid atherosclerosis and carotid artery and left ventricular hypertrophy.

The relationship of blood pressure (BP) variability to cardiovascular target-organ damage is controversial. Studies examining BP variability and left ventricular (LV) hypertrophy have been contradictory, and only limited data on the relation of BP variability to carotid atherosclerosis and carotid artery hypertrophy exist. BP variability was assessed as the standard deviation and coefficient of variation of awake and asleep pressures in 511 normotensive or untreated hypertensive subjects who underwent ambulatory BP monitoring and cardiac and carotid ultrasonography. Although the presence of focal carotid plaque was associated with an increase in ambulatory pressures and pressure variability, the differences in variability were eliminated by adjustment for age and absolute pressures. Similarly, LV mass was significantly related to BP variability, but the significance of this finding was eliminated after adjustment for important covariates. In multivariate analyses, age was the primary determinant of carotid artery cross-sectional area, with a weak but independent contribution from awake systolic and diastolic BP variability in addition to absolute pressure. BP variability was not independently related to either carotid or LV relative wall thickness, both measures of concentric remodeling. In the present study, awake BP variability was weakly but independently associated with carotid artery cross-sectional area, a measure of arterial hypertrophy. However, neither systolic nor diastolic BP variability was independently associated with carotid atherosclerotic plaque or LV mass.

Echocardiographic left ventricular geometry in hypertensive patients with electrocardiographic left ventricular hypertrophy: The LIFE Study.

AIM: To assess the prevalence of echocardiographic left ventricular hypertrophy (LVH) and concentric remodeling in hypertensive patients with electrocardiographic (ECG)-LVH and to estimate the cost-effectiveness of echocardiography and ECG for detection of LVH. DESIGN: Echocardiographic LV measurements and the prevalence of abnormal LV geometric patterns were compared between 964 hypertensive patients with ECG-LVH (Cornell voltage-duration product > 2440 and/or SV1 +/- RV5-6 > 38 mm) participating in the LIFE trial and groups of 282 employed hypertensives and 366 apparently normal adults. RESULTS: Among both women and men, stepwise increases from reference subjects to employed hypertensives to LIFE patients were observed for LV wall thicknesses, chamber size and mass. Mean LV mass/body surface area (BSA) and LV mass/height(2.7) were substantially larger in LIFE patients than normal adults among women (113 vs 69 g/m2 and 55 vs 32 g/m(2.7), p <0.001) and men (127 vs 83 g/m2 and 55 vs 36 g/m(2.7), p < 0.001), with intermediate values in employed hypertensives. Compared to the latter group, LIFE patients had higher prevalences of concentric LVH (25-29% vs 3-4%) and eccentric LVH (45-51% vs 13-17%) but not concentric LV remodeling (8-11% vs 12-14%). LVH was present in 70% of LIFE patients by LV mass/BSA criteria and 76% by LV mass/height(2.7) criteria (odds ratios = 11.4 and 13.5 vs employed hypertensives). CONCLUSIONS: The ECG criteria used in LIFE identify hypertensive patients with a >70% prevalence of anatomic LVH, allowing accurate identification of high-risk status by this commonly used technique.

Reference values for echocardiographic measurements in urban and rural populations of differing ethnicity: the Strong Heart Study.

Discrepancies in reported reference values for left ventricular (LV) dimensions and mass may be due to imaging errors with early echocardiographic methods or effects of subject characteristics and inclusion criteria. To determine whether contemporary echocardiographic methods provide stable normal limits for left ventricular measurements in different populations, M-mode/2-dimensional echocardiography was applied in 176 American Indian participants in the Strong Heart Study and 237 New York City residents who were clinically normal. No consistent difference in any measure of LV size or function existed between populations. Upper normal limits (98th percentile) for LV mass were 96 g/m(2) in women and 116 g/m(2) in men and 3.27 cm/m for LV chamber diameter normalized for height. Thus contemporary M-mode/2D echocardiography provides reference ranges for LV measurements that approximate necropsy measurements and have acceptable stability in apparently normal white, African-American/Caribbean, and American Indian populations.

Relation of age to left ventricular function and systemic hemodynamics in uncomplicated mild hypertension.

Previous studies in normotensive subjects have shown a slight decline in resting left ventricular pump function and midwall contractility with aging. We examined the relations of age to these variables and to peripheral resistance and vascular stiffness in 272 asymptomatic, unmedicated adults (25 to 80 years old) who had uncomplicated essential hypertension. Cardiac and carotid ultrasound and carotid pressure waveforms were obtained to measure left ventricular dimensions, endocardial and midwall left ventricular shortening, stroke index and cardiac index, end-systolic stress, and pulse pressure/stroke index and beta, pressure-dependent and independent measures of vascular stiffness, respectively. Endocardial and midwall stress-corrected left ventricular shortening assessed ventricular performance. Cardiac index and TPRI did not change with age in either gender, with age-related increases in systolic pressure offset by increasingly concentric ventricular geometry in women and enhanced ventricular systolic function in men. In contrast to the lack of age-related change in traditional hemodynamic indexes, pulse pressure/stroke volume and beta strongly increased with age (P<0.001). Thus, in uncomplicated, relatively mild essential hypertension, neither cardiac index nor peripheral resistance is associated with age. This hemodynamic stability is associated with age-related increased concentricity of ventricular geometry in women and increased ventricular performance indexes in hypertensive men. Vascular stiffness progressively increases with age, independent of change in mean pressure or resistance, possibly contributing to increased rates of cardiovascular events in older individuals.

The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: the Strong Heart Study.

OBJECTIVES: We sought to determine the effect of diabetes mellitus (DM) on left ventricular (LV) filling pattern in normotensive (NT) and hypertensive (HTN) individuals. BACKGROUND: Diastolic abnormalities have been extensively described in HTN but are less well characterized in DM, which frequently coexists with HTN. METHODS: We analyzed the transmitral inflow velocity profile at the mitral annulus in four groups from the Strong Heart Study: NT-non-DM (n = 730), HTN-non-DM (n = 394), NT-DM (n = 616) and HTN-DM (n = 671). The DM subjects were further divided into those with normal filling pattern (n = 107) and those with abnormal relaxation (AbnREL) (n = 447). RESULTS: The peak E velocity was lowest in HTN-DM, intermediate in NT-DM and HT-non-DM and highest in the NT-non-DM group (p < 0.001), with a reverse trend seen for peak A velocity (p < 0.001). In multivariate analysis, E/A ratio was lowest in HTN-DM and highest in NT-non-DM, with no difference between NT-DM and HTN-non DM (p < 0.001). Likewise, mean atrial filling fraction and deceleration time were highest in HTN-DM, followed by HTN-non-DM or NT-DM and lowest in NT-non-DM (both p < 0.05). Among DM subjects, those with AbnREL had higher fasting glucose (p = 0.03) and hemoglobin A1C (p = 0.04). CONCLUSIONS: Diabetes mellitus, especially with worse glycemic control, is independently associated with abnormal LV relaxation. The severity of abnormal LV relaxation is similar to the well-known impaired relaxation associated with HTN. The combination of DM and HTN has more severe abnormal LV relaxation than groups with either condition alone. In addition, AbnREL in DM is associated with worse glycemic control.

Identification of a chromosome 11q23.2-q24 locus for familial aortic aneurysm disease, a genetically heterogeneous disorder.

BACKGROUND: Aortic aneurysms cause significant mortality, and >20% relate to hereditary disorders. Familial aortic aneurysm (FAA) has been described in such conditions as the Marfan and Ehlers-Danlos type IV syndromes, due to defects in the fibrillin-1 and type III procollagen genes, respectively. Other gene defects that cause isolated aneurysms, however, have not thus far been described. METHODS AND RESULTS: We studied 3 families affected by FAA. No family met the diagnostic criteria for either Marfan or Ehlers-Danlos syndrome. Echocardiography defined involvement of both the thoracic and abdominal aorta. In family ANA, candidate gene analysis excluded linkage to loci associated with aneurysm formation, including fibrillin-1, fibrillin-2, and type III procollagen, and chromosome 3p24.2-p25. Genome-wide linkage analysis identified a 2.3-cM FAA locus (FAA1) on chromosome 11q23.3-q24 with a maximum multipoint logarithm of the odds score of 4.4. In family ANB, FAA was linked to fibrillin-1. In family ANF, however, FAA was not linked to any locus previously associated with aneurysm formation, including fibrillin-1 and FAA1. CONCLUSIONS: FAA disease is genetically heterogeneous. We have identified a novel FAA locus at chromosome 11q23.3-q24, a critical step toward elucidating 1 gene defect responsible for aortic dilatation. Future characterization of the FAA1 gene will enhance our ability to achieve presymptomatic diagnosis of aortic aneurysms and will define molecular mechanisms to target therapeutics.

Relationship of impaired glucose tolerance to left ventricular structure and function: The Strong Heart Study.

BACKGROUND: We have identified increased left ventricular (LV) mass, wall thickness, relative wall thickness, and reduced systolic function in diabetic individuals after adjusting for blood pressure and body mass index. However, the cardiovascular correlates of impaired glucose tolerance (IGT), a precursor of diabetes, are unknown. METHODS: We compared LV measurements between 457 American Indian participants in the Strong Heart Study with IGT (34% men) by World Health Organization criteria and 888 participants (49% men) with normal glucose tolerance. RESULTS: Participants with IGT were older (60 vs 59 years, P < .01), more overweight (body mass index, 32 +/- 6 vs 29 +/- 5 g/m(2)), and had higher systolic blood pressure (129 +/- 20 vs 124 +/- 18 mm Hg, P < .001) and heart rate (67 +/- 10 vs 66 +/- 11 beats/min, P = .011). In univariate analyses, women but not men with IGT had higher LV mass (mean, 150 vs 138 g, P < .001) and cardiac index (2.6 vs 2.5 L/min/m(2), P < .05). LV wall thicknesses and relative wall thickness were greater in women and men with IGT. Regression analysis, adjusting for multiple covariates in the entire study population, identified independent associations of IGT with higher LV relative wall thicknesses, LV mass/height(2.7), and cardiac output/height(1.83). CONCLUSIONS: IGT is associated with increased LV wall thickness, mass, and cardiac output independent of effects of relevant covariates.