Kenneth B. Schechtman

Effects of aging, sex, and physical training on cardiovascular responses to exercise.

BackgroundThe relative contributions of decreases in maximal heart rate, stroke volume, and oxygen extraction and of changes in body weight and composition to the age-related decline in maximal oxygen uptake (V˙o2max) are unclear and may be influenced by sex and level of physical activity. Methods and ResultsTo investigate mechanisms by which aging, sex, and physical activity influence V˙o2max, we quantified V˙o2, cardiac output, and heart rate during submaximal and maximal treadmill exercise and assessed weight and fat-free mass in healthy younger and older sedentary and endurance exercise-trained men and women. For results expressed in milliliters per kilogram per minute, a three-to-four-decade greater age was associated with a 40–41% lower V˙o2max in sedentary subjects and a 25–32% lower V˙o2max in trained individuals (p < 0.001). A smaller stroke volume accounted for nearly 50%o of these age-related differences, and the remainder was explained by a lower maximal heart rate and reduced oxygen extraction (all p < 0.001). Age-related effects on maximal heart rate and oxygen extraction were attenuated in trained subjects (p < 0.05). After normalization ofV˙o2max and maximal cardiac output to fat-free mass, age- and training-related differences were reduced by 24–47% but remained significant (p < 0.05). For trained but not sedentary subjects, maximal cardiac output and stroke volume normalized to fat-free mass were greater in men than in women (p < 0.05). ConclusionsA lower stroke volume, heart rate, and arteriovenous oxygen difference at maximal exercise all contribute to the age-related decline in V˙o2max. Effects of age and training on V˙o2max, maximal cardiac output, and stroke volume cannot be fully explained by differences in body composition. In sedentary subjects, however, the sex difference in maximal cardiac output and stroke volume can be accounted for by the greater percentage of body fat in women than in men.

Effect of Obesity and Insulin Resistance on Myocardial Substrate Metabolism and Efficiency in Young Women

Background—Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance. In the present study, we tested the hypothesis that myocardial fatty acid metabolism and efficiency are abnormal in obese women. Methods and Results—We studied 31 young women (body mass index [BMI] 19 to 52 kg/m2); 19 were obese (BMI >30 kg/m2). Myocardial oxygen consumption (M&OV0312;o2) and fatty acid uptake (MFAUp), utilization (MFAU), and oxidation (MFAO) were quantified by positron emission tomography. Cardiac work was measured by echocardiography, and efficiency was calculated as work/M &OV0312;o2. BMI correlated with M &OV0312;o2 (r =0.58, P =0.0006), MFAUp (r =0.42, P <0.05), and efficiency (r = −0.40, P <0.05). Insulin resistance, quantified by the glucose area under the curve (AUC) during an oral glucose tolerance test, correlated with MFAUp (r =0.55, P <0.005), MFAU (r =0.62, P <0.001), and MFAO (r =0.58, P <0.005). A multivariate, stepwise regression analysis showed that BMI was the only independent predictor of M&OV0312;o2 and efficiency (P =0.0005 and P <0.05, respectively). Glucose AUC was the only independent predictor of MFAUp, MFAU, and MFAO (P <0.05, <0.005, and <0.005, respectively). Conclusions—In young women, obesity is a significant predictor of increased M&OV0312;o2 and decreased efficiency, and insulin resistance is a robust predictor of MFAUp, MFAU, and MFAO. This increase in fatty acid metabolism and decrease in efficiency is concordant with observations made in experimental models of obesity. These metabolic changes may play a role in the pathogenesis of decreased cardiac performance in obese women.

Risk Factors for Early or Delayed Stroke After Cardiac Surgery

BACKGROUND Stroke after cardiac surgery is a devastating complication that leads to excess mortality and health resource utilization. The purpose of this study was to identify risk factors for perioperative stroke, including strokes detected early after cardiac surgery or postoperatively. METHODS AND RESULTS Data were obtained from 2972 patients undergoing coronary artery bypass graft and/or valve surgery. Patients >/=65 years old and those with a history of symptomatic neurological disease underwent preoperative carotid artery ultrasound scanning. Intraoperative epiaortic ultrasound to assess for ascending aorta atherosclerosis was performed in all patients. New strokes were considered as a single end point and were categorized with respect to whether they were detected immediately after surgery (early stroke) or after an initial, uneventful neurological recovery from surgery (delayed stroke). Strokes occurred in 48 patients (1.6%); 31 (65%) were delayed strokes. By multivariate analysis, prior neurological event, aortic atherosclerosis, and duration of cardiopulmonary bypass were independently associated with early stroke, whereas predictors of delayed stroke were prior neurological event, diabetes, aortic atherosclerosis, and the combined end points of low cardiac output and atrial fibrillation. Female sex was associated with a 6.9-fold increased risk of early stroke and a 1.7-fold increased risk of delayed stroke. In-hospital mortality of patients with early (41%) and delayed (13%) strokes was higher than that of other patients (3%, P=0.0001). CONCLUSIONS Most strokes after cardiac surgery occurred after initial uneventful recovery from surgery. Women were at higher risk to suffer early and delayed perioperative strokes. Atrial fibrillation had no impact on postoperative stroke rate unless it was accompanied by low cardiac output syndrome.

Effects of Exercise Training on Frailty in Community‐Dwelling Older Adults: Results of a Randomized, Controlled Trial

OBJECTIVES: Although deficits in skeletal muscle strength, gait, balance, and oxygen uptake are potentially reversible causes of frailty, the efficacy of exercise in reversing frailty in community‐dwelling older adults has not been proven. The aim of this study was to determine the effects of intensive exercise training (ET) on measures of physical frailty in older community‐dwelling men and women.

Development of the common data base for the FICSIT trials

The eight FICSIT (Frailty and Injuries: Cooperative Studies of Intervention Techniques) sites test different intervention strategies in selected target groups of older adults. To compare the relative potential of these interventions to reduce frailty and fall‐related injuries, all sites share certain descriptive (risk‐adjustment) measures and outcome measures. This article describes the shared measures, which are referred to as the FICSIT Common Data Base (CDB). The description is divided into four sections according to the four FICSIT committees responsible for the CDB: (1) psychosocial health and demographic measures; (2) physical health measures; (3) fall‐related measures; and (4) cost and cost‐effectiveness measures. Because the structure of the FICSIT trial is unusual, the CDB should expedite secondary analyses of various research questions dealing with frailty and falls.

The influence of location and extent of myocardial infarction on long-term ventricular dysrhythmia and mortality.

Although the extent of enzymatically estimated infarct size appears to be an important determinant of morbidity and mortality early after infarction, its influences on long-term survival and late ventricular dysrhythmia have not yet been characterized. Accordingly, we prospectively studied 173 patients younger than 66 years of age without evidence of prior myocardial infarction, who survived acute myocardial infarction for at least 24 hours. Infarct size was estimated enzymatically and dysrhythmia quantified by computer from two-channel, 24-hour ambulatory ECGs. The mean infarct size index (ISI) of those who died was significantly larger than that of survivors (46.5 ± 5.8 (SEM) vs 21.1 i 1.4 CK-g-Eq/m2, p < 0.001). Overall survival was significantly better after small (ISI < 15 CK-g-Eq/m2) or modest infarcts (15 < ISI < 30) than after large infarcts (ISI 30) (p < 0.01, p < 0.05, respectively). Regardless of the locus of the infarction, patients with small infarcts had a better prognosis than those with larger infarcts. Late mortality was comparable after transmural and subendocardial infarction, but higher after anterior than after inferior infarction (15% vs 6%; p < 0.05). Among the 10 clinical and hemodynamic variables evaluated with multivariate analysis, ISI (but not infarct locus), peak plasma creatine kinase, congestive failure at the time of admission, age and gender were significantly related to mortality. Premature ventricular complexes were more frequent among patients with modest or large infarcts (ISI 15) throughout the follow-up (p < 0.05), regardless of infarct locus. Thus, the extent of infarction is a strong determinant of both ventricular dysrhythmia and mortality, late as well as early after acute myocardial infarction.

Relationship Between Physical Performance and Self-Perceived Physical Function

OBJECTIVE: The objective of this study was to compare two methods of measuring physical function in subjects with a broad range of abilities and to evaluate the effects of cognitive, social, educational, and age factors on the relationship between the two methods.

1,25(OH)2 Vitamin D Inhibits Foam Cell Formation and Suppresses Macrophage Cholesterol Uptake in Patients With Type 2 Diabetes Mellitus

Background— Cardiovascular disease is the leading cause of death among those with diabetes mellitus. Vitamin D deficiency is associated with an increased risk of cardiovascular disease in this population. To determine the mechanism by which vitamin D deficiency mediates accelerated cardiovascular disease in patients with diabetes mellitus, we investigated the effects of active vitamin D on macrophage cholesterol deposition. Methods and Results— We obtained macrophages from 76 obese, diabetic, hypertensive patients with vitamin D deficiency (25-hydroxyvitamin D <80 nmol/L; group A) and 4 control groups: obese, diabetic, hypertensive patients with normal vitamin D (group B; n=15); obese, nondiabetic, hypertensive patients with vitamin D deficiency (group C; n=25); and nonobese, nondiabetic, nonhypertensive patients with vitamin D deficiency (group D; n=10) or sufficiency (group E; n=10). Macrophages from the same patients in all groups were cultured in vitamin D—deficient or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] –supplemented media and exposed to modified low-density lipoprotein cholesterol. 1,25(OH)2D3 suppressed foam cell formation by reducing acetylated or oxidized low-density lipoprotein cholesterol uptake in diabetic subjects only. Conversely, deletion of the vitamin D receptor in macrophages from diabetic patients accelerated foam cell formation induced by modified LDL. 1,25(OH)2D3 downregulation of c-Jun N-terminal kinase activation reduced peroxisome proliferated–activated receptor-γ expression, suppressed CD36 expression, and prevented oxidized low-density lipoprotein–derived cholesterol uptake. In addition, 1,25(OH)2D3 suppression of macrophage endoplasmic reticulum stress improved insulin signaling, downregulated SR-A1 expression, and prevented oxidized and acetylated low-density lipoprotein–derived cholesterol uptake. Conclusion— These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.

Strategy for the reduction of stroke incidence in cardiac surgical patients

Atherosclerosis of the ascending aorta (AAA) and severe carotid artery disease are risk factors for stroke in cardiac surgical patients. Twelve hundred of a consecutive series of 1,334 patients 50 years of age or older having a cardiac operation were screened for the presence of AAA by intraoperative ultrasonographic scanning and for the presence of carotid artery occlusive disease (791 of 798 patients > or = 65 years of age and younger symptomatic patients) by carotid duplex scanning. Coronary artery disease was present in 88% of the patients. Patients with moderate or severe AAA (n = 231; 19.3% of the total) were treated by ascending aortic replacement (n = 27) or by modified, less extensive techniques (n = 168) to avoid the atherosclerotic areas. Thirty-three patients had combined carotid endarterectomy and cardiac operation. Thirty-day mortality and stroke rates for the 1,200 patients were 4.0% and 1.6%, respectively. The stroke rate was low (1.1%) among the 969 patients with no or mild AAA. It was zero among 27 patients with moderate or severe AAA who had ascending aortic replacement and among the 33 patients who had carotid endarterectomy. The stroke rates were higher for 111 patients with moderate or severe ascending aortic disease who had only minor interventions (6.3%) and for 16 patients with severe carotid artery disease who did not have carotid endarterectomy (18.7%). Screening for AAA and carotid artery disease and aggressive surgical treatment of moderate or severe AAA and severe or symptomatic carotid artery disease appears to reduce the frequency of stroke in older cardiac surgical patients.

Atherosclerosis of the ascending aorta. Prevalence and role as an independent predictor of cerebrovascular events in cardiac patients.

The cause of cerebral and peripheral embolism remains undetermined in a significant number of patients. An atherosclerotic thoracic aorta has thus far been considered to be an uncommon one. Methods To define the potential role of the ascending thoracic aorta as an embolic source, intraoperative ultrasonic aortic imaging was performed in 1200 of 1334 consecutive patients aged 50 years and older who were undergoing cardiac surgery. Patients were divided into two groups according to the results of the ultrasound study in terms of presence or absence of atherosclerotic disease. The prevalence of previous neurological events in the two groups was characterized and compared. Results Ascending aortic atherosclerosis was present in 231 (19.3%) of the patients studied. Patients in this category were older (P<.0001). A higher percentage of them were smokers (P<.0001) compared with patients with less severe disease. Coronary artery disease was more extensive (P=.012), and a higher percentage of these patients had a history of peripheral vascular disease (P<.0001). Univariate analysis of the subjects with (n=158) and without (n=1042) previous neurological events indicated that age, body mass index, atrial fibrillation, hypertension, and atherosclerosis of the ascending aorta were associated significantly with previous occurrence of a cerebrovascular accident. For the group as a whole, multiple logistic regression analysis demonstrated that hypertension (odds ratio, 1.81; P=.002), atherosclerosis of the ascending aorta (odds ratio, 1.65; P=.013), and atrial fibrillation (odds ratio, 1.54; P=.060) were significantly and independently associated with the occurrence of previous neurological events. Conclusions Atherosclerosis of the ascending aorta is an independent risk factor for cerebrovascular events. An atherosclerotic ascending aorta may represent a potential source of emboli or may be a marker of generalized atherosclerosis.