Cardiometabolic risk in overweight subjects with or without relative fat-free mass deficiency: the Strong Heart Study.

BACKGROUND AND AIM: Sarcopenia is a condition mainly due to loss of fat-free mass (FFM) in elderly individuals. RFFMD, however, is also frequent in obese subjects due to abnormal body composition. Objective of this study was to evaluate the impact of relative fat-free mass deficiency (RFFMD) on cardiometabolic (CM) risk in obese normoglycemic individuals. METHODS AND RESULTS: Overweight/obese American Indians from the Strong Heart Study population, without diabetes and with FBG ≤ 110 mg/dL and with GFR >60 mg/mL/1.73 m(2) were selected for this analysis (n = 742). RFFMD was defined on the basis of a multivariable equation previously reported. Fasting glucose and 2 h-OGTT were measured together with urine albumin/creatinine excretion, laboratory and anthropometric parameters. In addition to lower FFM and greater adipose mass, participants with RFFMD had higher body mass index, waist circumference, C-reactive protein, fibrinogen, insulin resistance and urinary albumin/creatinine than participants with normal FFM (all p < 0.001); they also had a greater prevalence of hypertension, impaired glucose tolerance (IGT) or OGTT-diabetes than participants with normal FFM (all p < 0.003) and a near 2-fold greater probability of significant proteinuria (p < 0.01). RFFMD was more frequent in women than in men: significant sex-RFFMD interactions were found for BMI and waist circumference (both p < 0.0001). CONCLUSIONS: RFFMD in overweight/obese normoglycemic individuals is associated with greater probability of hypertension, abnormalities of glucose tolerance and proteinuria. Assessment of RFFRMD might, therefore, help stratifying cardiometabolic risk among normoglycemic individuals with overweight/obesity.

Serum uric acid does not predict incident metabolic syndrome in a population with high prevalence of obesity.

AIM: To evaluate whether uric acid (UA) predicts 4-yr incidence of metabolic syndrome (MetS) in non-diabetic participants of the Strong Heart Study (SHS) cohort. METHODS AND RESULTS: In this population-based prospective study we analyzed 1499 American Indians (890 women), without diabetes or MetS, controlled during the 4th SHS exam and re-examined 4 years later during the 5th SHS exam. Participants were divided into sex-specific tertiles of UA and the first two tertiles (group N) were compared with the third tertile (group H). Body mass index (BMI = 28.3 ± 7 vs. 31.1 ± 7 kg/m(2)), fat-free mass (FFM = 52.0 ± 14 vs. 54.9 ± 11 kg), waist-to-hip ratio, HOMA-IR (3.66 vs. 4.26), BP and indices of inflammation were significantly higher in group H than in group N (all p < 0.001). Incident MetS at the time of the 5th exam was more frequent in group H than group N (35 vs. 28%, OR 1.44 (95% CI = 1.10-1.91; p < 0.01). This association was still significant (OR = 1.13, p = 0.04) independently of family relatedness, sex, history of hypertension, HOMA-IR, central adiposity and renal function, but disappeared when fat-free mass was included in the model. CONCLUSIONS: In the SHS, UA levels are associated to parameters of insulin resistance and to indices of inflammation. UA levels, however, do not predict incident MetS independently of the initial obesity-related increased FFM.

In-treatment HDL cholesterol levels and development of new diabetes mellitus in hypertensive patients: the LIFE Study.

AIMS: Although hypertensive patients with low baseline HDL cholesterol levels have a higher incidence of diabetes mellitus, whether changing levels of HDL over time are more strongly related to the risk of new diabetes in hypertensive patients has not been examined. METHODS: Incident diabetes mellitus was examined in relation to baseline and in-treatment HDL levels in 7485 hypertensive patients with no history of diabetes randomly assigned to losartan- or atenolol-based treatment. RESULTS: During 4.7 ± 1.2 years follow-up, 520 patients (6.9%) developed new diabetes. In univariate Cox analyses, compared with the highest quartile of HDL levels (> 1.78 mmol/l), baseline and in-treatment HDL in the lowest quartile (< 1.21 mmol/l) identified patients with > 5-fold and > 9 fold higher risks of new diabetes, respectively; patients with baseline or in-treatment HDL in the 2nd and 3rd quartiles had intermediate risk of diabetes. In multivariable Cox analyses, adjusting for randomized treatment, age, sex, race, prior anti-hypertensive therapy, baseline uric acid, serum creatinine and glucose entered as standard covariates, and in-treatment non-HDL cholesterol, Cornell product left ventricular hypertrophy, diastolic and systolic pressure, BMI, hydrochlorothiazide and statin use as time-varying covariates, the lowest quartile of in-treatment HDL remained associated with a nearly 9-fold increased risk of new diabetes (hazard ratio 8.7, 95% CI 5.0-15.2), whereas the risk of new diabetes was significantly attenuated for baseline HDL < 1.21 mmol/l (hazard ratio 3.9, 95% CI 2.8-5.4). CONCLUSIONS: Lower in-treatment HDL is more strongly associated with increased risk of new diabetes than baseline HDL level.

Partial normalization of components of metabolic syndrome does not influence prevalent echocardiographic abnormalities: the HyperGEN study.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is a complex condition characterized by different phenotypes, according to the combinations of risk factors and is associated with cardiovascular abnormalities. Whether control of MetS components by treatment produces improvement in the associated cardiovascular abnormalities is unknown. We investigated whether partial control of components of MetS was associated with less echocardiographic abnormalities than the complete presentation of MetS based on measured components. METHODS AND RESULTS: We evaluated markers of echocardiographic preclinical cardiovascular disease in MetS (ATP III) defined by measured components or by history of treatment, in 1421 African-American and 1195 Caucasian non-diabetic HyperGEN participants, without prevalent cardiovascular disease or serum creatinine >2 mg/dL. Of 2616 subjects, 512 subjects had MetS by measured components and 328 by history. Hypertension was found in 16% of participants without MetS, 6% of those with MetS by history and 42% of those with MetS by measured components. Obesity and central fat distribution had similar prevalence in both MetS groups (both p < 0.0001 vs. No-MetS). Blood pressure was similar in MetS by history and No-MetS, and lower than in MetS by measured components (p < 0.0001). LV mass and midwall shortening, left atrial (LA) dimension and LA systolic force were similarly abnormal in both MetS groups (all p < 0.0001 vs. No-MetS) without difference between them. CONCLUSIONS: There is a little impact of control by treatment of single components of MetS (namely hypertension) on echocardiographic abnormalities. Lower blood pressure in participants with MetS by history was not associated with substantially reduced alterations in cardiac geometry and function.

Impact of overweight and obesity on cardiac benefit of antihypertensive treatment.

BACKGROUND AND AIMS: Increased body mass index (BMI) has been associated with increased cardiovascular morbidity and mortality in hypertension. Less is known about the impact of BMI on improvement in left ventricular (LV) structure and function during antihypertensive treatment. METHODS AND RESULTS: Annual BMI, echocardiograms and cardiovascular events were recorded in 875 hypertensive patients with LV hypertrophy during 4.8 years randomized treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy. Patients were grouped by baseline BMI into normal (n = 282), overweight (n = 405), obese (n = 150) and severely obese groups (n = 38) (BMI ≤24.9, 25.0-29.9, 30.0-34.9, and ≥35.0 kg/m(2), respectively). At study end, residual LV hypertrophy was present in 54% of obese and 79% of severely obese patients compared to 31% of normal weight patients (both p < 0.01). In regression analyses, adjusting for initial LV mass/height(2.7), higher BMI predicted less LV hypertrophy reduction and more reduction in LV ejection fraction (both p < 0.05), independent of blood pressure reduction, diabetes and in-study weight change. During follow-up, 91 patients suffered cardiovascular death, myocardial infarction or stroke. In Cox regression analysis 1 kg/m(2) higher baseline BMI predicted a 5% higher rate of cardiovascular events and 10% higher cardiovascular mortality over 4.8 years (both p < 0.05). CONCLUSIONS: In hypertensive patients in the LIFE study, increased BMI was associated with less reduction of LV hypertrophy and less improvement in LV systolic function which may contribute to the observed higher cardiovascular event rate of treated hypertensive patients.

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.

Impact of diabetes on treatment-induced changes in left ventricular structure and function in hypertensive patients with left ventricular hypertrophy. The LIFE study.

BACKGROUND AND AIM: Diabetes is associated with left ventricular hypertrophy (LVH) and impaired systolic function in hypertensive patients, but less is known about its impact on LVH regression and functional improvement during antihypertensive treatment. METHODS AND RESULTS: We performed annual echocardiography in 730 non-diabetic and 93 diabetic patients (aged 55-80 years) with hypertension and electrocardiographic LVH during 4.8-year losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Baseline mean blood pressure (BP) and LV mass did not differ between groups. Diabetic patients had higher body mass index and pulse pressure, and lower LV ejection fraction, midwall shortening, stress-corrected midwall shortening, and estimated glomerular filtration rate (all p<0.05), and were more likely to have albuminuria. Despite comparable BP reduction in diabetic and non-diabetic groups during treatment (33/18 vs. 28/16mmHg (ns)), diabetes was associated with higher prevalence of persistent LVH (47 vs. 39%, p<0.05). In multivariate analyses, diabetes independently predicted less LV mass reduction and less improvement in stress-corrected LV midwall shortening (both p<0.01). CONCLUSION: Among hypertensive patients with LVH, diabetes is associated with more residual LVH and less improvement in systolic LV function by echocardiography over 4.8 years of antihypertensive treatment.

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.

Clustered metabolic abnormalities blunt regression of hypertensive left ventricular hypertrophy: the LIFE study.

BACKGROUND AND AIMS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two or more metabolic abnormalities (MetAb, including obesity, high plasma glucose without diabetes, low HDL-cholesterol) in addition to hypertension were associated to levels of ECG LVH reduction comparable to that obtained in hypertensive subjects without or with only one additional metabolic abnormality (no-MetAb). METHODS AND RESULTS: We studied 5558 non-diabetic participants without MetAb (2920 women) and 1235 with MetAb (751 women) from the LIFE-study cohort. MetAb was defined by reported LIFE criteria, using partition values from the ATPIII recommendations. Time-trends of Cornell voltage-duration product (CP) over 5 years was assessed using a quadratic polynomial contrast, adjusting for age, sex, prevalent cardiovascular disease and treatment arm (losartan or atenolol). At baseline, despite similar blood pressures, CP was greater in the presence than in the absence of MetAb (p<0.0001). During follow-up, despite similar reduction of blood pressure, CP decreased less in patients with than in those without MetAb, even after adjustment for the respective baseline values (both p<0.002). Losartan was more effective than atenolol in reducing CP independently of MetAb. CONCLUSIONS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome are related to greater initial ECG LVH in hypertensive patients with value of blood pressure similar to individuals without metabolic abnormalities, and are associated with less reduction of ECG LVH during antihypertensive therapy, potentially contributing to the reported adverse prognosis of metabolic syndrome.

Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study.

The relation of metabolic syndrome (MetS) with cardiovascular outcome may be less evident when preclinical cardiovascular disease is present. We explored, in a post hoc analysis, whether MetS predicts cardiovascular events in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. MetS was defined by >or=2 risk factors plus hypertension: body mass index >or=30 kg/m(2), high-density lipoprotein (HDL)-cholesterol <1.0/1.3 mmol/l (<40/50 mg/dl) (men/women), glucose >or=6.1 mmol/l (>or=110 mg/dl) fasting or >or=7.8 mmol/l (>or=140 mg/dl) nonfasting or diabetes. Cardiovascular death and the primary composite end point (CEP) of cardiovascular death, stroke and myocardial infarction were examined. In MetS (1,591 (19.3%) of 8,243 eligible patients), low HDL-cholesterol (72%), obesity (77%) and impaired glucose (73%) were similarly prevalent, with higher blood pressure, serum creatinine and Cornell product, but lower Sokolow-Lyon voltage (all P<0.001). After adjusting for baseline covariates, hazard ratios for CEPs and cardiovascular death (4.8+/-1.1 years follow-up) were 1.47 (95% confidence interval (CI), 1.27-1.71)- and 1.73 (95% CI, 1.38-2.17)-fold higher with MetS (both P<0.0001), and were only marginally reduced when further adjusted for diabetes, obesity, low HDL-cholesterol, non-HDL-cholesterol, pulse pressure and in-treatment systolic blood pressure and heart rate. Thus, MetS is associated with increased cardiovascular events in hypertensive patients with ECG-LVH, independently of single cardiovascular risk factors.

Left ventricular geometry and function preceding neurally mediated syncope.

BACKGROUND: Neurally mediated syncope has been associated with increased left ventricular (LV) fractional shortening (FS) during tilt testing, which is consistent with the hypothesis that the stimulation of LV mechanoreceptors leads to reflex hypotension and/or bradycardia. However, FS does not represent true LV contractility because of its dependence on afterload and preload. METHODS AND RESULTS: To elucidate the role of increased contractility in the mediation of neurally mediated syncope, we compared echocardiographic measures of LV performance corrected for end-systolic stress (ESS) in 21 patients (13 women and 8 men) with unexplained syncope who had either positive (n=10) or negative (n=11) responses to a tilt-table test. Two-dimensional echocardiographic LV imaging was performed at baseline and during the initial 5 minutes of upright tilt. In the supine position, both groups had similar LV end-diastolic volume indexes, stroke volumes, FS, circumferential ESS, and afterload-independent measures of LV performance (stress-corrected midwall and FS). However, after 5 minutes of upright tilt, patients who subsequently had a positive test had a lower stroke volume, lower stress-corrected midwall shortening, and endocardial FS. The tilt-positive group also had a greater fall in ESS and FS early during upright tilt. CONCLUSIONS: Reduced ESS, LV volume, and chamber function during initial upright tilt are associated with a subsequent positive tilt response in patients with unexplained syncope. These data suggest that if paradoxic activation of LV mechanoreceptors has a role in mediating neurally mediated syncope, it is not triggered by LV hypercontractility or increased systolic wall stress during the initial period of upright tilt.

Relations of stroke volume and cardiac output to body composition: the strong heart study.

BACKGROUND: Although cardiac output (CO) plays the vital role of delivering nutrients to body tissues, few data are available concerning the relations of stroke volume (SV) and CO to body composition in large population samples. METHODS AND RESULTS: Doppler and 2D echocardiography and bioelectric impedance in 2744 Strong Heart Study participants were used to calculate SV and CO and to relate them to fat-free body mass (FFM), adipose mass, and demographic variables. Both SV and CO were higher in men than women and in overweight than normal-weight individuals, but these differences were diminished or even reversed by normalization for FFM or body surface area. In both sexes, SV and CO were more strongly related to FFM than adipose mass, other body habitus measures, arterial pressure, diabetes, or age. In multivariate analyses using the average of Doppler and left ventricular SV to minimize measurement variability, FFM was the strongest correlate of SV and CO; other independent correlates were adipose mass, systolic pressure, diabetes, age, and use of digoxin and calcium channel and beta-blockers. CONCLUSIONS: In a population-based sample, SV and CO are more strongly related to FFM than other variables; increased FFM may be the primary determinant of increased SV and CO in obesity.

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.

Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial.

BACKGROUND: The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) study was designed to test whether enalapril achieves greater left ventricular (LV) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis (10 g/m(2)). METHODS AND RESULTS: An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month randomized therapy. Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure (-22/12 versus -21/13 mm Hg) and LV mass index (-15 versus -17g/m(2), both P>0.20). No significant between-treatment difference was detected in population subsets defined by monotherapy treatment, sex, age, race, or severity of baseline hypertrophy. Similarly, there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow. More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide (59% versus 34%, P<0.001) but not atenolol (27% versus 22%, NS). CONCLUSIONS: Once-daily antihypertensive treatment with enalapril or long-acting nifedipine, plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure, both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy.

Impact of diabetes on cardiac structure and function: the strong heart study.

BACKGROUND: Whether diabetes mellitus (DM) adversely affects left ventricular (LV) structure and function independently of increases in body mass index (BMI) and blood pressure is controversial. METHODS AND RESULTS: Echocardiography was used in the Strong Heart Study, a study of cardiovascular disease in American Indians, to compare LV measurements between 1810 participants with DM and 944 with normal glucose tolerance. Participants with DM were older (mean age, 60 versus 59 years), had higher BMI (32.4 versus 28.9 kg/m(2)) and systolic blood pressure (133 versus 124 mm Hg), and were more likely to be female, to be on antihypertensive treatment, and to live in Arizona (all P<0.001). In analyses adjusted for covariates, women and men with DM had higher LV mass and wall thicknesses and lower LV fractional shortening, midwall shortening, and stress-corrected midwall shortening (all P<0.002). Pulse pressure/stroke volume, a measure of arterial stiffness, was higher in participants with DM (P<0.001 independent of confounders). CONCLUSIONS: Non-insulin-dependent DM has independent adverse cardiac effects, including increased LV mass and wall thicknesses, reduced LV systolic chamber and myocardial function, and increased arterial stiffness. These findings identify adverse cardiovascular effects of DM, independent of associated increases in BMI and arterial pressure, that may contribute to cardiovascular events in diabetic individuals.

Effect of type 2 diabetes mellitus on left ventricular geometry and systolic function in hypertensive subjects: Hypertension Genetic Epidemiology Network (HyperGEN) study.

BACKGROUND: Type 2 diabetes is a cardiovascular risk factor. It remains to be elucidated in a large, population-based sample whether diabetes is associated with changes in left ventricular (LV) structure and systolic function independent of obesity and systolic blood pressure (BP). METHODS AND RESULTS: Among 1950 hypertensive participants in the HyperGEN Study without overt coronary heart disease or significant valve disease, 20% (n=386) had diabetes. Diabetics were more likely to be women, black, older, and have higher BMI and waist/hip ratio than were nondiabetics. After adjustment for age and sex, diabetics had higher systolic BP, pulse pressure, and heart rate; lower diastolic BP; and longer duration of hypertension than nondiabetics. LV mass and relative wall thickness were higher in diabetic than nondiabetic subjects independent of covariates. Compared with nondiabetic hypertensives, diabetics had lower stress-corrected midwall shortening, independent of covariates, without difference in LV EF. Insulin levels and insulin resistance were higher in non-insulin-treated diabetics (n=195) than nondiabetic (n=1439) subjects (both P:<0.01). Insulin resistance positively but weakly related to LV mass and relative wall thickness. CONCLUSIONS: In a relatively healthy, population-based sample of hypertensive adults, type 2 diabetes was associated with higher LV mass, more concentric LV geometry, and lower myocardial function, independent of age, sex, body size, and arterial BP. structural and functional abnormalities in addition to, and independent of, atherosclerosis.(13) (14) In the Framingham cohort, diabetes was associated with higher LV mass in women but not men.(15) High blood pressure (BP), obesity, and abnormal lipid profile, which often coexist with diabetes, tend to be associated with preclinical cardiovascular abnormalities(16) and may contribute to the association of diabetes with cardiovascular events. Cardiac features of diabetic and nondiabetic hypertensive subjects remain incompletely described in population-based samples. Therefore, we compared clinical and metabolic characteristics, LV geometry, and systolic function between diabetic and nondiabetic hypertensive participants in the Hypertension Genetic Epidemiology Network (HyperGEN) Study.

Rising tide of cardiovascular disease in American Indians. The Strong Heart Study.

BACKGROUND: Although cardiovascular disease (CVD) used to be rare among American Indians, Indian Health Service data suggest that CVD mortality rates vary greatly among American Indian communities and appear to be increasing. The Strong Heart Study was initiated to investigate CVD and its risk factors in American Indians in 13 communities in Arizona, Oklahoma, and South/North Dakota. METHODS AND RESULTS: A total of 4549 participants (1846 men and 2703 women 45 to 74 years old) who were seen at the baseline (1989 to 1991) examination were subjected to surveillance (average 4.2 years, 1991 to 1995), and 88% of those remaining alive underwent a second examination (1993 to 1995). The medical records of all participants were exhaustively reviewed to ascertain nonfatal cardiovascular events that occurred since the baseline examination or to definitively determine cause of death. CVD morbidity and mortality rates were higher in men than in women and were similar in the 3 geographic areas. Coronary heart disease (CHD) incidence rates among American Indian men and women were almost 2-fold higher than those in the Atherosclerosis Risk in Communities Study. Significant independent predictors of CVD in women were diabetes, age, obesity (inverse), LDL cholesterol, albuminuria, triglycerides, and hypertension. In men, diabetes, age, LDL cholesterol, albuminuria, and hypertension were independent predictors of CVD. CONCLUSIONS: At present, CHD rates in American Indians exceed rates in other US populations and may more often be fatal. Unlike other ethnic groups, American Indians appear to have an increasing incidence of CHD, possibly related to the high prevalence of diabetes. In the general US population, the rising prevalence of obesity and diabetes may reverse the decline in CVD death rates. Therefore, aggressive programs to control diabetes and its risk factors are needed.

Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease.

BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Day-to-day variability of voltage measurements used in electrocardiographic criteria for left ventricular hypertrophy.

Although electrocardiographic (ECG) voltage can be used to estimate left ventricular mass, day-to-day variability of voltage combinations used for this purpose must be established before ECG changes are taken as evidence of progression or regression of hypertrophy. Accordingly, serial ECGs (mean 8 days apart), derived from 10 s samples digitized at 250 Hz, were examined in 78 patients with no intercurrent change in clinical status. The coefficient of variation was calculated as 1 SD of the difference between paired voltage measurements, divided by the average mean value. Coefficient of variation for single leads was 22.3% for SV1, 27.0% for RV5 or RV6, 27.1% for RaVL and 34.7% for SV3. Coefficient of variation was lower for voltage combinations than for individual lead measurements: 18.5% for Sokolow-Lyon voltage (SV1 + RV5 or RV6), 22.3% for Gubner-Ungerleider voltage (R1 + S3) and 24.8% for Cornell voltage (RaVL + SV3). Serial reclassification due to variation above and below standard criteria for left ventricular hypertrophy occurred in only 3% of patients for Sokolow-Lyon voltage and 4% of patients for Cornell voltage in this group. Minute to minute reproducibility of voltage was assessed with electrodes in place in a separate group of 26 patients, and the coefficient of variation was 2.6% for Sokolow-Lyon voltage, 5.9% for Gubner-Ungerleider voltage and 2.9% for Cornell voltage. These data indicate that serial variability of computer-measured ECG voltage combinations is high, due primarily to changes in lead placement and body position, but less than the variability of computer-measured voltage in individual leads.