The large cohort of white men (317,871) 35 to 57 years old at initial screening for possible enrollment into the Multiple Risk Factor Intervention Trial (MRFIT) was examined with regard to initial blood pressure levels and subsequent coronary heart disease (CHD), stroke, and all-cause mortality. The overall prevalence of isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) less than 90 mm Hg, was 0.67% among white men screened for MRFIT and increased with age (0.31% among 35- to 39-year-olds to 1.7% among 55- to 57-year-olds). The 6 year CHD and all-cause mortality rates in men over 50 were highest in those with ISH compared with both subjects with diastolic hypertension and those with normal pressure. The relative risk of death from stroke in those with ISH, compared with that in those with SBP less than 160 mm Hg and those with DBP less than 90 mm Hg, was 3.0 (95% confidence interval 1.3 to 6.8). In addition, at any level of DBP, the level of SBP appeared to be the major determinant of all-cause and CHD mortality. The determinants of ISH in individuals under 60 years of age as well as the possible efficacy of its treatment should be evaluated further.

The noninvasive determination of maximal oxygen uptake or VO2max, defined as a plateau in VO2 during incremental treadmill exercise, is an objective, reproducible, and negotiable measure of the severity of chronic cardiac or circulatory failure. Moreover, this noninvasive variable predicts the exercise cardiac output response and thereby the cardiac reserve. The lactate or anaerobic threshold has been validated in these patients from the response of mixed venous lactate to incremental exercise and has been shown to be another objective measure of the severity of chronic cardiac or circulatory failure. The anaerobic threshold can be reliably assessed from the response in breath-by-breath respiratory gas exchange by the use of multiple criteria, several of which can be monitored during the exercise test itself and the remainder of which can be measured during the recovery period. We find the breath-by-breath monitoring of respiratory gas exchange and air flow to provide the best means of assessing the anaerobic threshold and for identifying the plateau in VO2, or VO2max, in response to incremental treadmill exercise.

Engagement in muscular exercise involves complex local and nervous adjustments of the circulation. In the active muscles, including cardiac muscle, the resistance vessels relax in response to local chemical changes to provide an increase in blood flow adequate for their metabolic requirements. There is increased release of norepinephrine from the sympathetic nerve endings as a result of increased sympathetic outflow; the resultant alpha-receptor activation leads to constriction of both systemic resistance and capacitance vessels outside the active muscles, and the beta-receptor activation leads to an increase in heart rate, shortening of the refractory period, and enhancement of myocardial contractility. As a consequence, the filling pressure of the heart and arterial blood pressure are maintained, and the increase in left ventricular output is directed primarily to the active muscles. During upright exercise, the action of the leg muscle pump contributes to the maintenance of the cardiac filling pressure. As exercise continues and body temperature rises, the skin flow increases to dissipate heat from the body. Static exercise causes a greater increase in arterial blood pressure than dynamic exercise. This is due to the combination of an increase in cardiac output and in total systemic vascular resistance as a consequence of increase sympathetic outflow and mechanical compression of the vessels in the active muscles. The hemodynamic changes result from activation of ergoreceptors in the contracted muscles and from central command. The increase in pressure helps to oppose the mechanical compression. The arterial baroreceptors are reset so that they operate normally around the higher blood pressure.

During exercise, the level of oxygen consumption (VO2) above which aerobic energy production is supplemented by anaerobic mechanisms causing a sustained increase in lactate and metabolic acidosis is termed the anaerobic threshold. The VO2 at which the anaerobic threshold occurs is influenced by the factors that affect oxygen delivery to the tissues, being increased when oxygen flow is enhanced and decreased when oxygen flow is diminished. The anaerobic threshold is an important functional demarcation since the physiologic responses to exercise are different above the anaerobic threshold as compared with below the anaerobic threshold. Above the anaerobic threshold, in addition to the development of metabolic acidosis, exercise endurance is reduced, VO2 kinetics are slowed so that a steady state is delayed, and minute ventilation increases disproportionately to the metabolic requirement and a progressive tachypnea develops. The anaerobic threshold can be measured directly from lactate concentration with good threshold detection from a log-log transformation of lactate and VO2. This threshold defines the VO2 at which the lactate/pyruvate ratio increases. As bicarbonate changes reciprocally with lactate, its measurement can also be used to estimate the lactate threshold. But most conveniently, changes in gas exchange caused by the physical-chemical event of buffering of lactic acid by bicarbonate can be used to detect the anaerobic threshold during exercise.

Power outputs that are below the anaerobic threshold (theta an) may be sustained for prolonged durations, whereas power outputs that are greater than theta an result in a significant reduction in the tolerable duration to fatigue. The theta an may therefore be considered to demarcate exercise intensity into moderate (below) and heavy (above) domains. O2 uptake (VO2) responds with linear first-order dynamics for sub-theta an power outputs with a time constant of approximately equal to 25 to 35 sec and a "delay" of 15 to 20 sec. A steady state is therefore normally achieved within 3 min. For supra-theta an exercise an additional, slower component of VO2 delays the steady state (if attainable). This slow phase of the VO2 response causes the VO2 to rise to values above the steady-state level attainable by fitter subjects at that work rate. The magnitude of this "excess" VO2 correlates highly with the increased arterial blood lactate [L-] and becomes marked when [L-] exceeds 4 to 5 meq/liter. The theta an may therefore be considered a crucial index for sustainable physical activity that is not--or is modestly--fatiguing.

Exercise testing has assumed a position of growing importance in the assessment of patients with chronic congestive heart failure. The hemodynamic and neurohumoral adjustments that occur during dynamic exercise are very complex, but are basically designed to ensure that oxygen delivery is commensurate with oxygen demand. These responses are clearly altered in the presence of certain types of heart disease. Patients with chronic congestive heart failure have an attenuated heart rate and blood pressure response throughout exercise, but this is most clearly evident when the data are expressed as a percent of peak oxygen consumption (VO2) rather than as a function of absolute VO2. Likewise, the sympathetic response to exercise is altered in patients with heart failure. Plasma norepinephrine is normally augmented as a function of VO2 during exercise, but this augmentation occurs during the later stages (beyond 50% of peak VO2). Patients with congestive heart failure show a greater than normal augmentation of plasma norepinephrine during exercise when the data are expressed in terms of absolute VO2. However, when the data are expressed as a percent of peak VO2, there appears to be a relative attenuation of the sympathetic response to exercise. Current information suggests that increased plasma norepinephrine and renin activity during exercise in patients with heart failure are not directly related to a decrement in nutritive blood flow to skeletal muscles. The mechanisms responsible for exercise intolerance in patients with heart failure are not known, but do not seem directly related to a decrement in cardiac output or an increase in left ventricular filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

A review of the experimental clinical trials and observational cohort evidence relating serum cholesterol level and its reduction to risks of coronary heart disease (CHD) discloses strong similarities among the quantitative and qualitative relationships found in these studies. Not only are the risk functions similar, but the percent reduction observed is the same as that predicted from the population experience and is proportional to the degree of cholesterol lowering. Furthermore, the risk function is continuous from the highest to the lowest serum cholesterol levels studied. These findings confirm the lipid hypothesis and indicate that lowering serum cholesterol reduces CHD risk. The understanding and control of CHD requires a dual approach: (1) identification and treatment of high-risk individuals, and (2) modification of environmental and behavioral determinants to achieve more favorable distributions of serum cholesterol in populations.

In summary, a variety of nuclear techniques may be used to investigate the effects of thrombolytic therapy and myocardial reperfusion. Assessments of global and regional ventricular function, myocardial perfusion, and metabolic integrity are available and appear to add substantially to conventional assessment. Timing of studies appears to be critical. Complementary data can be obtained in both the acute and convalescent phase of myocardial infarction.