Brain natriuretic peptide and insulin resistance in older adults.

AIMS: Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established. METHODS: N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance. RESULTS: Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic = 71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP). CONCLUSIONS: In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study.

The association of lean and fat mass with all-cause mortality in older adults: The Cardiovascular Health Study.

BACKGROUND AND AIMS: Understanding contributions of lean and fat tissue to cardiovascular and non-cardiovascular mortality may help clarify areas of prevention in older adults. We aimed to define distributions of lean and fat tissue in older adults and their contributions to cause-specific mortality. METHODS AND RESULTS: A total of 1335 participants of the Cardiovascular Health Study (CHS) who underwent dual-energy x-ray absorptiometry (DEXA) scans were included. We used principal components analysis (PCA) to define two independent sources of variation in DEXA-derived body composition, corresponding to principal components composed of lean ("lean PC") and fat ("fat PC") tissue. We used Cox proportional hazards regression using these PCs to investigate the relationship between body composition with cardiovascular and non-cardiovascular mortality. Mean age was 76.2 ± 4.8 years (56% women) with mean body mass index 27.1 ± 4.4 kg/m2. A greater lean PC was associated with lower all-cause (HR = 0.91, 95% CI 0.84-0.98, P = 0.01) and cardiovascular mortality (HR = 0.84, 95% CI 0.74-0.95, P = 0.005). The lowest quartile of the fat PC (least adiposity) was associated with a greater hazard of all-cause mortality (HR = 1.24, 95% CI 1.04-1.48, P = 0.02) relative to fat PCs between the 25th-75th percentile, but the highest quartile did not have a significantly greater hazard (P = 0.70). CONCLUSION: Greater lean tissue mass is associated with improved cardiovascular and overall mortality in the elderly. The lowest levels of fat tissue mass are linked with adverse prognosis, but the highest levels show no significant mortality protection. Prevention efforts in the elderly frail may be best targeted toward improvements in lean muscle mass.

Increased right ventricular wall thickness in left ventricular pressure overload: echocardiographic determination of hypertrophic response of the "nonstressed" ventricle.

Left ventricular hypertrophy in left ventricular pressure overload occurs in response to excessive work load imposed on the left ventricle by increased impedance to ejection. Right ventricular hypertrophy may occur in patients with these findings, but has been considered to be secondary to pulmonary hypertension. To determine the frequency of right ventricular hypertrophy and its relation to increased left ventricular wall thickness in patients with left ventricular pressure overload, right ventricular wall thickness was measured using M-mode echocardiography with two-dimensional echocardiographic guidance in 65 patients with left ventricular pressure overload; 49 patients had essential hypertension and 16 had aortic valve stenosis. These measurements were compared with data from 13 patients with "thin-walled" dilated cardiomyopathy and 20 normal subjects. Average right ventricular wall thickness in hypertensive patients (7 +/- 2 mm) and patients with aortic stenosis (6 +/- 2 mm) was significantly greater than that in normal subjects (4 +/- 1 mm) and patients with dilated cardiomyopathy (4 +/- 1 mm) who had normal left ventricular wall thickness, even though left ventricular mass was increased in all patient groups. Increased right ventricular wall thickness was present in 40 (80%) of 49 patients with hypertension and 10 (63%) of 16 patients with aortic stenosis. The magnitude of increase in right ventricular wall thickness was linearly correlated (r = 0.76, p less than 0.005) with left ventricular wall thickness, but was not associated with pulmonary hypertension. It is concluded that increased right ventricular wall thickness is common in patients with left ventricular pressure overload, is directly related to increases in left ventricular wall thickness, and is independent of right ventricular hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Should echocardiography be performed to assess effects of antihypertensive therapy? Test-retest reliability of echocardiography for measurement of left ventricular mass and function.

OBJECTIVES: The purpose of this study was to determine the test-retest stability of echocardiography for the measurement of left ventricular mass and function in patients with hypertension. BACKGROUND: Determination of changes in left ventricular mass may be impaired by study variability. The amount by which variables of mass and left ventricular function must change in an individual patient to exceed temporal variability has not been determined in a multicenter trial. METHODS: Ninety-six patients with hypertension had two-dimensional targeted, M-mode Doppler echocardiography repeated at 6 +/- 8 days by the same technician utilizing the same machine. Left ventricular mass and variables of systolic and diastolic function were measured. Test-retest reliability and the width of the 95% confidence intervals of variable change, as well as the contributions of age, study quality and body size to measurement reliability, were determined. RESULTS: Despite excellent reliability (intraclass coefficient of correlation 0.86), the 95% confidence interval width of a single replicate measurement of left ventricular mass was 59g, exceeding usual decreases in mass during treatment. Study quality, which was dependent on age and weight, influenced test reliability. Although the confidence interval width for ejection fraction was narrow (5 U), those for peak early (E) and late (A) diastolic velocities were wide, resulting in a confidence interval width for the E/A ratio of 1.5. CONCLUSIONS: The temporal variability, particularly in obese or elderly patients, or both, of echocardiography for measurement of left ventricular mass precludes its use to measure changes in mass of the magnitude likely to occur with therapy. Measurement stability is affected by study quality, and age and body weight both influence study quality. Although ejection fraction shows little temporal variability, the large width of the confidence interval of the Doppler E/A ratio impairs its use to serially measure diastolic function.

Predictive value of systolic and diastolic function for incident congestive heart failure in the elderly: the cardiovascular health study.

OBJECTIVES: We sought to assess the ability of echocardiographic indices of systolic and diastolic function to predict incident congestive heart failure (CHF). BACKGROUND: Noninvasive indices of subclinical systolic and/or diastolic dysfunction that can be used to identify patients in a transition phase between normal cardiac function and clinical CHF would be valuable. Though midwall shortening and Doppler mitral inflow patterns are seemingly well suited to predict subsequent CHF, the predictive value of these indices has not been investigated. METHODS: We studied 2,671 participants in the Cardiovascular Health Study who were free of coronary heart disease, CHF or atrial fibrillation. Clinical and quantitative echocardiographic data were obtained in all participants. RESULTS: At a mean follow-up of 5.2 years (range 0 to 6 years), 170 participants (6.4% of the cohort) developed CHF. Although 96% of these participants had normal or borderline ejection fraction (EF) at baseline, only 57% had normal or borderline EF at the time of hospitalization. In multivariate modeling, fractional shortening at the endocardium (relative risk [RR] 1.85 per 10-unit decrease, confidence interval [CI] 1.27 to 2.39), fractional shortening at the midwall (RR 1.29 per five-unit decrease, 95% CI 1.11-1.51) and peak Doppler peak E (RR 1.15 for each 0.1 M/s increment; CI 1.02 to 1.21) independently predicted incident CHF. Both high and low Doppler E/A ratios were predictive of incident CHF. CONCLUSIONS: Roughly half the occurrences of CHF in this population are associated with normal or borderline EF. Echocardiographic findings suggestive of subclinical contractile dysfunction and diastolic filling abnormalities are both predictive of subsequent CHF. The standard (FSendo) and refined (FSmw) parameters of systolic function performed similarly in this regard, though subjects with left ventricular hypertrophy and depressed FSmw are at particularly high risk for subsequent CHF.

Prevalence of valvular-regurgitation associated with dexfenfluramine three to five months after discontinuation of treatment.

OBJECTIVES: The goal of this study was to determine the prevalence of valvular regurgitation and abnormal valve morphology in patients three to five months after discontinuation of dexfenfluramine (Dexfen) therapy. BACKGROUND: We previously reported the results of a randomized, double-blind, placebo-controlled trial of valvular structure and function in 1,073 patients treated either with Dexfen, with an investigational sustained-release dexfenfluramine (Dexfen SR), or with a placebo, with echocardiograms performed approximately one month from the last dose. Using FDA criteria (aortic regurgitation [AR] > or =mild and/or mitral regurgitation [MR] > or =moderate) we found no statistical difference among the groups, but when all degrees of valvular regurgitation were considered and when the two Dexfen groups were combined, there was a higher prevalence of any degree of AR, any degree of MR, and restricted posterior mitral leaflet mobility. However, it was unknown whether these differences in prevalence persisted. METHODS: The double blind was maintained, and all patients were invited to return for a follow-up echocardiogram. Echocardiograms were acquired using a standardized protocol and assessed blindly to determine the degree of valvular regurgitation and valve leaflet thickness and mobility. We had an 80% power to detect a statistically significant change in paired proportions using the McNemar test (alpha = 0.05). RESULTS: Echocardiograms were obtained on 941 patients with a median of 137 days after drug discontinuation. Aortic regurgitation (of any degree) was present in 13.8% of Dexfen (p = 0.41 compared to placebo), 10.7% of Dexfen SR (p = 0.64 compared to placebo), and 11.9% of placebo patients. The minor differences between patients treated with active drug versus placebo, which were found in the previous study, were no longer significant even when the groups were combined (p = 0.83 compared to placebo). Mitral regurgitation (of any degree) was present in 71.5% (p = 0.15 compared to placebo), 69.8% (p = 0.30 compared to placebo), and 70.5%, respectively. This was also not significantly different from placebo when both Dexfen groups were combined (p = 0.16). There was no difference in the prevalence of restricted posterior mitral leaflet mobility among the three groups (p = 0.19). CONCLUSIONS: The small increase in prevalence of minor degrees of AR and MR in patients treated with two to three months of Dexfen previously reported is no longer present three to five months after discontinuation of medication. These data suggest that the degree of regurgitation observed in patients who used Dexfen for a relatively short duration does not progress over time.

Left atrial size in hypertensive men: influence of obesity, race and age. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

OBJECTIVES: We sought to determine the relations of left atrial (LA) size to blood pressure, obesity, race, age and left ventricular (LV) mass in hypertension. BACKGROUND: Although obesity, race and age may influence LV mass, their effects on LA size have not been defined in hypertension. METHODS: Left atrial size was measured in 690 men (58% African-Americans) with mild to moderate hypertension (mean [+/-SD] blood pressure 152 +/- 15/98 +/- 6 mm Hg) and a high prevalence of LV hypertrophy. Effects of LV mass, adiposity, race, age, physical activity, height, weight, sodium excretion, plasma renin activity and heart rate were examined. RESULTS: Left atrial size was greater (p < or = 0.0001) in obese (44.2 +/- 5.7 mm) than in overweight (41.6 +/- 5.9 mm) or normal weight (38.9 +/- 6.2 mm) patients. Left atrial enlargement (> or = 43 mm) was present in 56% of obese patients compared with 42% of overweight and 25% of normal weight hypertensive men. As age increased, white patients had a greater LA size than African-American patients. Although there was no relation between LV mass and LA size in normal weight patients, there was a significant positive relation in obese patients. On multiple regression analysis, obesity was the strongest independent predictor of increased LA size. CONCLUSIONS: Obesity is the strongest predictor of LA size in patients with hypertension and amplifies the relation between LA size and LV mass. Race influences effects of age and hypertension on LA size. Because increased LA size and LV mass (also influenced by obesity) are associated with an adverse outcome, these findings underscore the importance of obesity, race and age with regard to the cardiac effects of hypertension.

Epidemiological approach to quality assessment in echocardiographic diagnosis.

OBJECTIVES: This study sought to determine whether statistical analysis of a computerized clinical diagnostic database can be used as a tool for quality assessment by determining the contribution of reader bias to variance in diagnostic output. BACKGROUND: In industry, measurement of product uniformity is a key component of quality assessment. In echocardiography, quality assessment has focused on review of small numbers of cases, or prospective determination of reader variability in selected and relatively small subsets. However, diagnostic biases in clinical practice might be discerned utilizing large computerized databases to determine interreader differences in diagnostic prevalence and, with use of appropriate statistical methods, to determine the association of reader selection with diagnostic prevalence independently of other covariates. METHODS: We analyzed 6,026 echocardiograms in a computerized database, read by one of three level 3 (American Society of Echocardiography) readers, for differences in frequency among four coded echocardiographic diagnoses: mitral valve prolapse, valvular vegetations, left ventricular (LV) thrombus, and LV regional wall-motion abnormality. RESULTS: Significant differences (up to fourfold) were found between readers, which persisted after statistical adjustment for those population characteristics, which differed slightly between readers. The low population prevalence of these conditions would have made it unlikely that these interreader differences could be detected by nonstatistical methods. Additionally, chamber dimensions differed between readers and were not normally distributed. CONCLUSIONS: Statistically based quality assessment analysis of computerized clinical databases facilitates ongoing monitoring of interreader bias despite low diagnostic prevalence, and targets opportunities for subsequent quality improvement.

Dynamic subaortic obstruction in hypertrophic cardiomyopathy: analysis by pulsed Doppler echocardiography.

To determine whether true obstruction to left ventricular ejection exists in patients with hypertrophic cardiomyopathy and a subaortic gradient, pulsed Doppler echocardiography was used to analyze the patterns of left ventricular emptying in 50 patients with hypertrophic cardiomyopathy (20 with and 30 without evidence of obstruction) and in 20 normal subjects. In obstructive hypertrophic cardiomyopathy, left ventricular ejection was characterized by early and rapid emptying (76 +/- 14% of aortic flow velocity in the initial one-third of systole). The proportion of forward flow velocity occurring before initial mitral-septal contact (and hence, by inference before the onset of the subaortic gradient) was variable, but averaged 58%. In contrast, the proportion of forward flow velocity occurring after mitral-septal contact (and, therefore, concomitant with the gradient and increased intraventricular pressure) was considerable, averaging over 40%. Mid-systolic impedance to left ventricular outflow was suggested by the rapid deceleration in aortic flow velocity concomitant with mitral-septal contact and premature partial aortic valve closure. Furthermore, left ventricular ejection was prolonged (384 +/- 40 ms) and the ventricle continued to empty and shorten during the period when both the pressure gradient and markedly increased intraventricular pressures were present. In 16 of 20 patients, a relatively small second peak in flow velocity appeared in late systole. Since marked systolic anterior motion of the mitral valve was still present, the late systolic portion of forward flow velocity also appeared to be largely ejected during imposition of a mechanical impediment to outflow. In contrast, patients with nonobstructive hypertrophic cardiomyopathy showed no evidence of impedance to left ventricular ejection. Aortic flow velocity waveforms were similar to those of normal subjects, with flow persisting to aortic valve closure; significant mitral systolic anterior motion and partial mid-systolic aortic valve closure were absent, and the systolic ejection period was normal (303 +/- 27 ms).(ABSTRACT TRUNCATED AT 400 WORDS)

Specificity of Doppler echocardiography for the assessment of changes in valvular regurgitation: comparison of side-by-side versus serial interpretation.

OBJECTIVES: We sought to determine the specificity of two different methods for assessing change in aortic (AR), mitral (MR) and tricuspid (TR) valvular regurgitation. BACKGROUND: Echocardiographic imaging with Doppler is the standard noninvasive diagnostic tool for assessing valvular structure and function. Change can be assessed using either independent evaluations (serial) or using a side-by-side comparison. METHODS: Subjects were from the placebo arm of a randomized, double-blind, clinical trial. Three echocardiograms over 10 months were performed. An initial and three-month echocardiogram were read as independent groups, blinded to all parameters except sequence. The initial and 10-month echocardiograms were read side-by-side, blinded to all parameters including sequence. RESULTS: Two hundred nineteen predominantly healthy, obese, white, middle-aged women had initial and three-month echocardiograms (acquisition interval 105 +/- 28 days) evaluated by the serial method (mean 167 +/- 61 days between interpretations). The same subjects had the initial and 10-month studies (acquisition interval 303 +/- 27 days) compared side-by-side. The specificity of the serial versus side-by-side method for determining change in MR grade was 55.8% versus 93.2% (p < 0.001); TR: 63.8% versus 97.6% (p < 0.001) and AR: 93.7% versus 97.6 (p = 0.08). Notably, most of the change occurred in a range (none versus physiologic/mild) that has limited clinical significance. Furthermore, the percentage of echocardiograms interpreted as nonevaluable was lower with the side-by-side method for MR (5.0% vs. 16.0%, p = 0.06), TR (4.6% vs. 15.5%, p < 0.001) and AR (4.1% vs. 12.3%, p = 0.002). CONCLUSIONS: The side-by-side method of assessing change in valvular regurgitation appears to be the more reliable method with a higher specificity and minimal data loss.

Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial.

OBJECTIVES: The echocardiographic contrast-enhancing effects and safety profile of ALBUNEX (a suspension of air-filled albumin microspheres) were compared with the new contrast agent OPTISON (formerly FS069: a suspension of albumin microspheres containing the gas perfluoropropane) in 203 patients with inadequate noncontrast echocardiograms. BACKGROUND: The efficacy of ALBUNEX has been limited by its short duration of action. By using perfluoropropane instead of air within the microsphere, its duration of action is increased. METHODS: Each patient received ALBUNEX (0.8 and 0.22 mL/kg) and OPTISON (0.2, 0.5, 3.0, and 5.0 mL) on separate days a minimum of 48 hours apart. Echocardiograms were evaluated for increase in left ventricular (LV) endocardial border length, degree of LV opacification, number of LV endocardial border segments visualized, conversion from a nondiagnostic to a diagnostic echocardiogram, and duration of contrast enhancement. A thorough safety evaluation was conducted. RESULTS: Compared with ALBUNEX, OPTISON more significantly improved every measure of contrast enhancement. OPTISON increased well-visualized LV endocardial border length by 6.0+/-5.1, 6.9+/-5.4, 7.5+/-4.7, and 7.6+/-4.8 cm, respectively, for each of the four doses, compared with only 2.2+/-4.5 and 3.4+/-4.6 cm, respectively, for the two ALBUNEX doses (p < 0.001). 100% LV opacification was achieved in 61%, 73%, 87%, and 87% of the patients with the four doses of OPTISON, but in only 16% and 36% of the patients with the two ALBUNEX doses (p < 0.001). Conversion of nondiagnostic to diagnostic echocardiograms with contrast occurred in 74% of patients with the optimal dose of OPTISON (3.0 mL) compared with only 26% with the optimal dose of ALBUNEX (0.22 mL/kg) (p < 0.001). The duration of contrast effect was also significantly greater with OPTISON than with ALBUNEX. In a subset of patients with potentially poor transpulmonary transit of contrast (patients with chronic lung disease or dilated cardiomyopathy), OPTISON more significantly improved the same measures of contrast enhancement compared with ALBUNEX and did so to the same extent as in the overall population. Side effects were similar and transient with the two agents. CONCLUSION: OPTISON appears to be a safe, well-tolerated echocardiographic contrast agent that is superior to ALBUNEX.

Induction of silent myocardial ischemia with mental stress testing: relation to the triggers of ischemia during daily life activities and to ischemic functional severity.

OBJECTIVES: This study examined the relations among the triggers of ischemia during the activities of daily life, mental stress-induced ischemia in the laboratory and functional severity of ischemia on exercise testing. BACKGROUND: Myocardial ischemia is readily induced with exercise testing, but most episodes of ischemia in daily life occur during relatively sedentary activities. Although mental and emotional arousal are known to trigger myocardial ischemia, mental stress testing induces ischemia in only approximately 50% of patients with active coronary disease. It is not known whether such patients are particularly susceptible to nonexertional ischemia during daily activity. METHODS: We studied 45 men (mean age +/- SD 58 +/- 9 years) with coronary artery disease by means of 48-h Holter ambulatory electrocardiography for ST segment analysis and quantification of physical and mental activity with a structured diary system. These data were cross-tabulated with new left ventricular dyssynchrony (detected on two-dimensional echocardiography) induced by two mental stressors and by bicycle exercise. RESULTS: During mental stress testing, 24 patients (53%) (Group I) had a new wall motion abnormality; the other 21 patients (Group II) did not. The average wall motion dyssynchrony score increased from 1.20 +/- 0.29 to 1.34 +/- 0.36 (p = 0.001), but the increase was less than that with exercise stress (1.52 +/- 0.41, p = 0.001). The total duration of ischemia during sedentary activities was greater in Group I (22.9 +/- 24.5 min) than in Group II (3.6 +/- 3.9 min, p = 0.025). Group I had more ischemic events while sedentary (23 of 290 diary entries) than did Group II (8 of 256 diary entries, p = 0.015). The magnitude of dyssynchrony with mental stress and the number of mental stressors capable of triggering ischemia were related to severity of ischemia with exercise. CONCLUSIONS: Patients with ischemia during mental stress testing also have increased ischemia during sedentary activities in daily life. This finding may reflect greater functional severity of coronary artery disease or a propensity toward coronary vasoconstriction while sedentary.

Changes in heart rate and heart rate variability before ambulatory ischemic events(1).

OBJECTIVES: The aim of this study was to determine the time course of autonomic nervous system activity preceding ambulatory ischemic events. BACKGROUND: Vagal withdrawal can produce myocardial ischemia and may be involved in the genesis of ambulatory ischemic events. We analyzed trajectories of heart rate variability (HRV) 1 h before and after ischemic events, and we examined the role of exercise and mental stress in preischemic autonomic changes. METHODS: Male patients with stable coronary artery disease (n = 19; 62.1 +/- 9.3 years) underwent 48-h ambulatory electrocardiographic monitoring. Frequency domain HRV measures were assessed for 60 min before and after each of 68 ischemic events and during nonischemic heart rate-matched control periods. RESULTS: High-frequency HRV decreased from -60, -20 to -10 min before ischemic events (4.8 +/- 1.3; 4.6 +/- 1.3; 4.4 +/- 1.2 ln [ms(2)], respectively; p = 0.04) and further from -4, -2 min, until ischemia (4.4 +/- 1.3; 4.1 +/- 1.3; 3.7 +/- 1.2 ln [ms(2)]; p's < 0.01). Low frequency HRV decreases started at -4 min (p < 0.05). Ischemic events occurring at high mental activities were preceded by depressed high frequency HRV levels compared with events at low mental activity (p = 0.038 at -4 min, p = 0.045 at -2 min), whereas the effects of mental activities were not observed during nonischemic control periods. Heart rate variability measures remained significantly decreased for 20 min after recovery of ST-segment depression when events were triggered by high activity levels. CONCLUSIONS: Autonomic changes consistent with vagal withdrawal can act as a precipitating factor for daily life ischemia, particularly in episodes triggered by mental activities.

Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: relationship with hemodynamic stress responses.

OBJECTIVES: This study examines the prevalence and hemodynamic determinants of mental stress-induced coronary vasoconstriction in patients undergoing diagnostic coronary angiography. BACKGROUND: Decreased myocardial supply is involved in myocardial ischemia triggered by mental stress, but the determinants of stress-induced coronary constriction and flow velocity responses are not well understood. METHODS: Coronary vasomotion was assessed in 76 patients (average age 59.9 +/- 10.4 years; eight women). Coronary flow velocity responses were assessed in 20 of the 76 patients using intracoronary Doppler flow. Repeated angiograms were obtained after a baseline control period, a 3-min mental arithmetic task and administration of 200 microg intracoronary nitroglycerin. Arterial blood pressure (BP) and heart rate assessments were made throughout the procedure. RESULTS: Mental stress resulted in significant BP and heart rate increases (p < 0.001). Coronary constriction (>0.15 mm) was observed in 11 of 59 patients with coronary artery disease (CAD) (18.6%). Higher mental stress pressor responses were associated with more constriction in diseased segments (rdeltaSBP = -0.26, rdeltaDBP = -0.30, rdeltaMAP = -0.29; p's < 0.05) but not with responses in nonstenotic segments. The overall constriction of diseased segments was not significant (p > 0.10), whereas a small but significant constriction occurred in nonstenotic segments (p = 0.04). Coronary flow velocity increased in patients without CAD (32.2%; p = 0.008), but not in patients with CAD (6.4%; p = ns). Cardiovascular risk factors were not predictive of stress-induced vasomotion in patients with CAD. CONCLUSIONS: Coronary vasoconstriction in angiographically diseased arteries varies with hemodynamic responses to mental arousal. Coronary flow responses are attenuated in CAD patients. Thus, combined increases in cardiac demand and concomitant reduced myocardial blood supply may contribute to myocardial ischemia with mental stress.

Triggers of myocardial ischemia during daily life in patients with coronary artery disease: physical and mental activities, anger and smoking.

OBJECTIVES: This study assessed the potency of physical and mental activities and emotions (anger and anxiety) and smoking and other substance use as proximate triggers of ischemia in patients with coronary artery disease during daily life. BACKGROUND: Myocardial ischemia occurs during a wide variety of activities in patients with coronary artery disease, but frequency and relative potency of physical and mental activities, smoking and use of caffeine and alcohol as triggers of ischemia during daily life have not been established. METHODS: Patients (n = 63) with coronary artery disease and evidence of out-of-hospital ischemia kept a validated structured diary of physical and mental activities and psychologic states while undergoing ambulatory electrocardiographic monitoring for 24 to 48 h. RESULTS: Ischemia occurred most frequently during moderately intense physical and mental activities. Patients spent the largest proportion of time engaged in low intensity physical and mental activities (p < 0.05), but the likelihood of ischemia was greatest during intense physical (p < 0.0001) and stressful mental activities (p < 0.03). The percentage of time in ischemia was elevated and approximately equivalent for high intensity physical and high intensity mental activities (5%) compared with 0.2% when patients were engaged in low intensity activities. Strenuous physical activity (e.g., effortful walking, p < 0.05) and the experience of intense anger were potent ischemic triggers, and heart rates at onset of ischemia increased with the intensity of physical and mental activity and with anger. Among smokers, ischemia was more than five times as likely when patients smoked than when they did not (during 24% vs. 5% of diary entries, p < 0.0001). Coffee and alcohol consumption were also related to ischemia (p < 0.05), but this association disappeared after controlling for concurrent cigarette smoking. CONCLUSIONS: Triggers of ischemia in patients with coronary artery disease during daily life include not only strenuous exercise, but also activities involving low levels of exertion, such as anger and smoking. Mental activities appear to be as potent as physical activities in triggering daily life ischemia. Coffee and alcohol consumption are related to ischemia only by virtue of their associations with smoking.

Importance of obesity, race and age to the cardiac structural and functional effects of hypertension. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

OBJECTIVES: The purpose of this study was to determine the effects of obesity and its interaction with age, race and the magnitude of blood pressure elevation in a large cohort of patients with mild to moderate hypertension and a high prevalence of left ventricular hypertrophy. BACKGROUND: Obesity, race and age each have important effects on the incidence and severity of hypertension and may contribute to the effects of blood pressure elevation on the cardiac manifestations of hypertension. METHODS: Left ventricular structure and function were assessed with two-dimensional targeted M-mode echocardiography in 692 men with mild to moderate hypertension (average blood pressure 153/100 mm Hg), and the data were compared in relation to obesity (determined from body mass index), age, race, blood pressure, physical activity, plasma renin activity, urinary sodium excretion, hematocrit, heart rate and serum lipids. RESULTS: Left ventricular hypertrophy was common (63% with increased left ventricular mass, 22% with left ventricular hypertrophy on the electrocardiogram [ECG]). On multivariable regression analysis, body mass index was the strongest predictor of left ventricular mass and magnified the slope relation of blood pressure to left ventricular mass. Despite a greater prevalence of ECG left ventricular hypertrophy in blacks (31%) than in whites (10%), left ventricular mass and echocardiographic prevalence of left ventricular hypertrophy did not differ by race. However, septal, posterior left ventricular and relative wall thickness were greater in black than in white men. CONCLUSIONS: Obesity is the strongest clinical predictor of left ventricular mass and left ventricular hypertrophy in men, even in those with mild to moderate hypertension of sufficient severity to be associated with a high prevalence of left ventricular hypertrophy. Moreover, independent effects of systolic blood pressure on left ventricular mass are amplified by obesity. Although race does not affect left ventricular mass or the prevalence of left ventricular hypertrophy, black race is associated with greater relative wall thickness, itself a predictor of unfavorable cardiovascular outcome.

Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study.

OBJECTIVES: The aim of this study was to determine the prevalence of aortic sclerosis and stenosis in the elderly and to identify clinical factors associated with degenerative aortic valve disease. BACKGROUND: Several lines of evidence suggest that degenerative aortic valve disease is not an inevitable consequence of aging and may be associated with specific clinical factors. METHODS: In 5,201 subjects > or = 65 years of age enrolled in the Cardiovascular Health Study, the relation between aortic sclerosis or stenosis identified on echocardiography and clinical risk factors for atherosclerosis was evaluated by using stepwise logistic regression analysis. RESULTS: Aortic valve sclerosis was present in 26% and aortic valve stenosis in 2% of the entire study cohort; in subjects > or = 75 years of age, sclerosis was present in 37% and stenosis in 2.6%. Independent clinical factors associated with degenerative aortic valve disease included age (twofold increased risk for each 10-year increase in age), male gender (twofold excess risk), present smoking (35% increase in risk) and a history of hypertension (20% increase in risk). Other significant factors included height and high lipoprotein(a) and low density lipoprotein cholesterol levels. CONCLUSIONS: Clinical factors associated with aortic sclerosis and stenosis can be identified and are similar to risk factors for atherosclerosis.

Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group.

OBJECTIVES: We sought to determine the efficacy of isradipine in reducing left ventricular (LV) mass and wall thickness in hypertensive patients. BACKGROUND: LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events. Reduction of LV mass may be a desirable goal of drug therapy for hypertension. However, although thiazide diuretic drugs have been advocated as first-line therapy for hypertension, their efficacy in reducing LV mass has been questioned. METHODS: Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were randomized to isradipine (n = 89) or hydrochlorothiazide therapy (n = 45). Evaluations were obtained at baseline, after 3 and 6 months of treatment and 2 weeks after treatment was stopped. RESULTS: At 6 months, LV mass decreased by 43 +/- 45 g (mean +/- SD) with hydrochlorothiazide (p < 0.001) but only by 11 +/- 48 g with isradipine (p = NS; between-group comparison, p < 0.001). Two weeks after drug therapy was stopped, LV mass remained 24 +/- 41 g lower than that at baseline in the hydrochlorothiazide group (p = 0.003) but only 7 +/- 50 g lower in the isradipine group (p = NS). Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide. Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 +/- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine. At 6 months of treatment, diastolic blood pressure (BP) by design was equally reduced in both treatment groups. At 3 months, systolic BP was reduced by 17 +/- 15 mm Hg with isradipine and by 26 +/- 15 and 25 +/- 17 mm Hg at 3 and 6 months, respectively, with hydrochlorothiazide (p = 0.003, between-group comparison). However, on stepwise multivariable regression analysis, treatment selection (partial r2 = 0.082, p = 0.001), change in average 24-h systolic BP (partial r2 = 0.032, p = 0.029) and change in average sitting systolic BP (partial r2 = 0.017, p = 0.096) were predictive of LV mass reduction. CONCLUSIONS: Despite an equivalent reduction of diastolic BP, 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass, greater than that with isradipine. The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself. These data may have important therapeutic implications.

Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study.

OBJECTIVES: We sought to characterize the predictors of incident congestive heart failure (CHF), as determined by central adjudication, in a community-based elderly population. BACKGROUND: The elderly constitute a growing proportion of patients admitted to the hospital with CHF, and CHF is a leading source of morbidity and mortality in this group. Elderly patients differ from younger individuals diagnosed with CHF in terms of biologic characteristics. METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of 5,888 elderly people >65 years old (average 73 +/- 5, range 65 to 100) at four locations. Multiple laboratory measures of cardiovascular structure and function, blood chemistries and functional assessments were obtained. RESULTS: During an average follow-up of 5.5 years (median 6.3), 597 participants developed incident CHF (rate 19.3/1,000 person-years). The incidence of CHF increased progressively across age groups and was greater in men than in women. On multivariate analysis, other independent predictors included prevalent coronary heart disease, stroke or transient ischemic attack at baseline, diabetes, systolic blood pressure (BP), forced expiratory volume 1 s, creatinine >1.4 mg/dl, C-reactive protein, ankle-arm index <0.9, atrial fibrillation, electrocardiographic (ECG) left ventricular (LV) mass, ECG ST-T segment abnormality, internal carotid artery wall thickness and decreased LV systolic function. Population-attributable risk, determined from predictors of risk and prevalence, was relatively high for prevalent coronary heart disease (13.1%), systolic BP > or =140 mm Hg (12.8%) and a high level of C-reactive protein (9.7%), but was low for subnormal LV function (4.1%) and atrial fibrillation (2.2%). CONCLUSIONS: The incidence of CHF is high in the elderly and is related mainly to age, gender, clinical and subclinical coronary heart disease, systolic BP and inflammation. Despite the high relative risk of subnormal systolic LV function and atrial fibrillation, the actual population risk of these for CHF is small because of their relatively low prevalence in community-dwelling elderly people.

Five-year follow-up of Friedreich's ataxia cardiomyopathy.

Ten patients with Friedreich's ataxia were reexamined at a five-year follow-up with electrocardiography and echocardiography. The three patients who initially had had the smallest left ventricular diastolic dimensions relative to their body surface areas (decreased 23% to 25% below predicted dimensions) had undergone dilatation of their left ventricles and atria, with decreasing fractional shortening of the left ventricle, but stable to decreasing ventricular wall thickness. The other seven patients, whose ventricular diastolic dimensions were initially closer to those predicted for their body surface areas, had not undergone significant dilatation. However, their left ventricular posterior walls and interventricular septa had thickened at a mean rate of 0.019 mm/mo. The interplay of these tendencies to hypertrophy and dilatation may explain the disagreement about the type of hypertrophic cardiomyopathy in Friedreich's ataxia.