Thomas R. Griggs

Is physical activity or aerobic power more influential on reducing cardiovascular disease risk factors

PURPOSE This study determined the relationship between aerobic power (VO2max), physical activity (PA), and cardiovascular disease (CVD) risk factors. The study also determined how increased VO2max and increased PA levels influence CVD risk factors of 576 low-fit adults (VO2max < 30 mL.kg-1.min-1). METHODS PA (Baeke questionnaire) and VO2max (submaximal cycle test) of 1664 law enforcement trainees were evaluated with respect to the CVD risk factors of total cholesterol, blood pressure (BP) [BP], smoking, and obesity using separate logistic regression, adjusting for age, gender, and the other major CVD risk factors. RESULTS Compared with the lowest tertile of VO2max, the highest tertile had a reduced relative risk (RR) for elevated cholesterol (RR, 0.56; CI, 0.36-0.43), BP (RR, 0.32; CI, 0.15-0.62) and obesity (RR, 0.09; CI, 0.06-0.12). The middle tertile of VO2max compared with the lowest had reduced RR for elevated diastolic BP (RR, 0.44; CI, 0.23-0.66) and obesity (RR: 0.38; CI 0.28-0.50). High PA tertile, compared with low PA tertile, only had lower RR for high systolic BP (RR, 0.48; CI, 0.23-0.95). Compared with the low PA tertile, moderate or high PA had no reduction in any of the RR (P > 0.05). Participation in a 9-wk exercise program by low-fit individuals resulted in a 9% increase in PA levels (P < 0.02); however, only those subjects who increased VO2max (> 3 mL.kg-1.min-1; N = 345) had a reduction in RR for high cholesterol (RR: 0.62; CI 0.42-0.92) and systolic BP (RR: 0.57; CI 0.40-0.80). No reduction in RR were noted for diastolic BP or obesity. CONCLUSIONS Aerobic power appears to have more of an influence on CVD risk factors than PA levels. Further, in low-fit persons, it appears that PA resulting in an increased aerobic power is associated with a reduction in CVD risk factors of cholesterol and BP in as little as 9 wk.

Heart rates in fire fighters using light and heavy breathing equipment: Similar near-maximal exertion in response to multiple work load conditions

Intense exertion is an occupational hazard inherent to fire fighting. This study was designed to look at the exertion levels that fire fighters attain during a fire fighting exercise when using (1) no self-contained breathing apparatus (SCBA), (2) light SCBA, and (3) heavy SCBA. Exertion levels were measured as a function of the heart rate increase relative to the maximum predicted heart rate determined by a standard treadmill exercise test. Five fire fighters wore electrocardiographic monitors during a routine fire fighting exercise. Heart rates increased rapidly to 70% to 80% of maximum within the first minute and then plateaued at 90% to 100% until the attack on the fire was completed. There was no significant difference between exertion levels when using no SCBA, light SCBA, and heavy SCBA (split-plot analysis of variance, p greater than .25). These results suggest that fire fighters attain an intense level of physical activity quickly and maintain that level as long as they are actively engaged in fighting fire. These results also suggest that regardless of the weight of the SCBA, if employed, fire fighters exert themselves from 85% to 100% of their maximum and adjust their work output to maintain that near-maximal level.

Von Willebrand factor and occlusive arterial thrombosis: A study in normal and von Willebrand's disease pigs with diet-induced hypercholesterolemia and atherosclerosis

The thrombotic response of atherosclerotic arteries to stenosis and injury was studied in 14 pigs, eight normal and six with von Willebrands disease (vWD). Atherosclerosis was produced by feeding a 1% to 2% cholesterol diet for 24 weeks. Both groups of pigs developed severe hypercholesterolemia, greater than five times baseline values. Coronary atherosclerosis was detected in all vWD pigs and in all but one normal pig and was not significantly different between groups. At sacrifice under general anesthesia, a Goldblatt clamp (GC) was positioned around the left anterior descending coronary (LAD) and carotid arteries to produce a stenotic segment, which was pinch-injured with needle holders. A 20 MHz Doppler velocity crystal was placed distal to the GC to detect cyclic flow reductions or permanent cessation of flow velocity indicative of occlusive thrombosis. In the phenotypically normal pigs with diet-induced atherosclerosis, occlusive thrombosis was detected in seven of seven LAD and seven of seven carotid arteries. In atherosclerotic vWD pigs, occlusive thrombosis failed to form in six LAD and 10 carotid arteries (p less than 0.003, Wilcoxon rank sum test). Scanning electron micrographs demonstrated platelet-fibrin microthrombi in both groups of pigs; only phenotypically normal pigs had occlusive thrombi. Von Willebrand factor is essential for the development of occlusive thrombosis and appears to support the progression of a mixed microthrombus to an occlusive thrombus.

Assessment of platelet activation by coronary sinus blood sampling during balloon angioplasty and directional coronary atherectomy

Three markers of platelet activation (platelet-derived microparticles, fibrinogen binding and expression of P-selectin) were assessed by flow cytometry during diagnostic coronary angiography and therapeutic coronary interventions. In 24 patients undergoing diagnostic angiography, blood was collected to determine if our sampling techniques or coronary angiography caused platelet activation. Changes during diagnostic angiography were used to establish baseline values and interpret changes during coronary interventions. In 21 patients, blood samples were obtained at 5 time points during percutaneous transluminal coronary angioplasty (PTCA) (n = 17) or directional coronary atherectomy (DCA) (n = 4). During coronary interventions, mean values for the percentage of platelets expressing P-selectin or binding fibrinogen increased, but with considerable variation among patients. Individual responses for platelet activation markers in each patient were characterized using a twofold increase to indicate elevation related to the intervention. Patients were classified as having complicated or uncomplicated procedures based on the presence of acute closure, dissection, or thrombus observed by angiography. There were no differences in the percentage of elevated markers between patients with uncomplicated (12.5%) and complicated (19%) PTCA procedures. However, patients treated with DCA had more elevated markers (38%) than those treated with PTCA (15%) (p = 0.04). Our data suggest that the extent of platelet activation in individual patients cannot be predicted by common angiographic findings or complications. More markers of platelet activation were present after DCA and may reflect a greater degree of vascular trauma associated with this procedure.

von Willebrand factor and animal models: contributions to gene therapy, thrombotic thrombocytopenic purpura, and coronary artery thrombosis.

Use of animal models of von Willebrand factor (vWF) deficiency, both inherited and induced, continues to advance the knowledge of vWF-related diseases. Three examples are reviewed in this article--von Willebrands disease (vWD), thrombotic thrombocytopenic purpura, and coronary artery thrombosis. The success of gene transfer by liver and bone marrow transplantation in porcine vWD and canine hemophilia A, with a change in phenotype that establishes improved hemostasis, portends imminent testing of gene therapy in these models. With use of recombinant technology, the phenotype of hemophilia B fibroblasts has been transformed to normal, as evidenced by secretion of the normal hemostatically active protein. This result is a prelude to implantation in hemophilic animals. Thrombotic thrombocytopenic purpura is characterized by qualitative and quantitative alterations in vWF. A new animal model induced by the venom factor botrocetin, a cofactor of vWF, closely mimics the human syndrome. A proposed pathophysiologic mechanism for thrombotic thrombocytopenic purpura is outlined. The third contribution is recognition that occlusive coronary thrombosis is a vWF-dependent condition. Without vWF, as in porcine vWD or normal pigs treated with a monoclonal anti-vWF antibody, occlusive thrombi do not develop, even with luminal stenosis. The thrombogenicity of coronary atheromas, including those with fissures of the fibrous cap, is also vWF-dependent.

Development of coronary atherosclerosis in swine with severe hypercholesterolemia. Lack of influence of von Willebrand factor or acute intimal injury.

The development of coronary atherosclerosis in response to acute intimal injury and severe hypercholesterolemia was studied in 18 swine, nine normal and nine with von Willebrands disease, an inherited disorder affecting platelet-vessel wall interactions. The left anterior descending coronary artery was denuded of endothelium by balloon catheterization, while the circumflex and right coronary arteries served as nonballooned controls. All swine were maintained on a 2% cholesterol diet for 4 months. The extent of atherosclerotic involvement was evaluated from four indices: percent intimal area, percent luminal narrowing, ratio of intimal to medial area, and luminal form. No differences in coronary atherosclerosis were observed between phenotypes in either ballooned or nonballooned vessels, nor were there any differences between ballooned and nonballooned vessels within either phenotype (p > 0.05). The major variable affecting coronary atherosclerosis was serum cholesterol. There was a significant positive relationship between serum cholesterol concentration and the extent of intimal lesions (r = 0.62, p = 0.006) that was independent of plasma von Willebrand factor concentration. These findings suggest that severe hypercholesterolemia promotes the development of porcine coronary atherosclerosis through a mechanism(s) that is independent of acute intimal injury or von Willebrand factor-mediated platelet response to injury.

PATHOPHYSIOLOGY OF PLATELET‐AGGREGATING von WILLEBRAND FACTOR: APPLICATIONS OF THE VENOM COAGGLUTININ vWF ASSAY*

The term “von Willebrand factor” (vWF) applies to one or more physiological or functional activities of plasma that are deficient in subjects with severe von Willebrand‘s disease (vWD), excluding the antihemophilic factor (AHF) . All of these activities are contained in the macromolecular factor VIII complex. The functional von Willebrand activities are several and include the bleeding time corrective factor, the AHF-stimulating factor, and the platelet-aggregating effect. The first two are recognized by in vivo procedures; the latter by in vitro procedures. The bleeding time corrective factor is ordinarily determined by the conversion of a long bleeding time to a normal or shortened bleeding time after transfusion of factor VIII into subjects with severe von Willebrand‘s disease. This corrective action is presumably mediated by adhesion of platelets to injured vessel wall and tissue. It has been proposed that determination of the extent of trapping of platelets in glass bead columns is a possible in vitro method for detecting and assessing the amount of this bleeding time factor, but both adhesion of platelets to glass beads as well as trapping of clumps of platelet aggregates occur. The AHF-stimulating factor, like the bleeding time corrective factor, is identified after transfusion of fractions into subjects with severe von Willebrands disease. The presence of this factor is indicated by a rise in the plasma antihemophilic factor (coagulant factor VIII or VII1:C) 12 to 48 hours later. This late rise in AHF is in contrast to the immediate rise in plasma AHF seen with replacement therapy in both hemophilia and von Willebrand‘s disease. The platelet-aggregating factor is assayed by one of several in vitro methods, as indicated later. In addition to the physiologically based procedures, several immunologic procedures exist for measuring factor VIII-related antigen, which appears to be related to at least two of the functional activities of the macromolecular factor VIII complex, the platelet-aggregating von Willebrand factor and the antihemophilic factor. This presentation will be mainly limited to a consideration of the functional or nonimmunologic aspects of the vWF activities and will discuss a new procedure for studying the platelet-aggregating vWF, the venom coagglutinin test.

Effect of carbon monoxide on atherogenesis in normal pigs and pigs with von Willebrand's disease

The extent of coronary and aortic atherosclerosis was examined in pigs following balloon-catheter injury of coronary arteries and subsequent feeding of an atherogenic diet for 4 months. The pigs were either exposed intermittently to 100 ppm carbon monoxide or to ambient air alone. Three types of pigs were used: normals, homozygotes for von Willebrands disease (bleeders), and heterozygotes (carriers). The 3 types of pigs developed coronary artery intimal lesions of similar thickness. Aortic lesions, quantified as percent of aortic surface involved with sudanophilia and raised fibrous plaques, were slightly less extensive in bleeder pigs than in normals. Carbon monoxide exposure did not increase the thickness of coronary artery intimal lesions, nor did it increase the percent of aortic surface involved with sudanophilia or raised fibrous lesions. These results suggest that exposure to low levels of carbon monoxide does not perceptibly enhance atherogenesis induced by hypercholesterolemia. None of 14 bleeder pigs showed evidence of myocardial infarction, despite significant coronary artery narrowing. Of the 24 normal and carrier pigs, 5 showed myocardial infarction. Four of these 5 pigs were exposed to carbon monoxide, while 1 was not exposed. These findings suggest that exposure to low levels of carbon monoxide may increase the incidence of myocardial infarction and that the absence of von Willebrand factor may be protective.

von Willebrand Factor Does Not Influence Atherogenesis in Arteries Subjected to Altered Shear Stress

The role of von Willebrand factor (vWF) in arterial neointimal formation that develops in arteries with altered shear stress was investigated using normal, heterozygous, and homozygous von Willebrand disease pigs (ie, vWD, or lacking vWF) that were fed normal pig chow. Shear stress was applied to carotid and femoral arteries with a Goldblatt clamp for 14 days, producing a > or = 80% stenosis. Neointimal lesion size was measured by computer-assisted morphometry. Expression of proliferative cell nuclear antigen (PCNA) by neointimial and medial cells was used as a relative index of proliferative activity. For shear-stressed arteries, there was no significant difference in the number of smooth muscle cell layers in the lesion, lesion size, and percent of PCNA-positive neointimal or medial cells among normal, heterozygous, and homozygous vWD pigs (P> or =.1, ANOVA). Lesions in pigs that expressed vWF (normals and heterozygotes) contained large amounts of vWF in the neointima, whereas lesions in vWD pigs had no detectable vWF. Moreover, no foam cells were detected in the lesions. Thus, the absence of vWF apparently does not alter the size of lesions in shear-stressed arteries in vWD pigs or the number of neointimal or medial cells expressing PCNA. Mechanism(s) involved with shear-induced modulation of smooth muscle cell proliferation, then, can operate independently of vWF in normolipemic pigs.

An Occupation Based Physical Activity Intervention Program Improving Fitness and Decreasing Obesity

The purpose of this quasi-experimental study was to determine the effectiveness of an occupation based health and fitness program. Subjects were 1,504 police trainees (85% male, 15% female) with an ethnic distribution of 82% white, 16% African American, and 2% other. Data were collected at 25 sites across the state of North Carolina. The sites were randomly assigned to either the experimental group (implemented the intervention) or the control group (continued usual training). As compared with controls, subjects at the experimental sites improved significantly in cardiovascular fitness (aerobic power), general muscular strength (number of sit ups per minute), and flexibility, and lowered their body fat. The intervention required minimal equipment and was taught primarily by peers who received a 1 week training program. This occupational approach to improving health could be particularly useful in occupations with many workers who seldom engage in leisure time physical activity.