The association between cardiovascular risk factors and major cardiovascular diseases decreases with increasing frailty levels in geriatric outpatients.

BACKGROUND: Frailty marks a process of increasing dysregulation of physiological systems which increases the risk of adverse health outcomes. This study examines the hypothesis that the association between multiple cardiovascular risk factors (CVRF) and cardiovascular diseases (CVD) becomes stronger with increasing frailty severity. METHODS: Cross-sectional analysis of 339 older adults (55.2% women; aged 75.2 ±â€¯9.1 years) from an outpatient geriatric clinic from a middle-income country. The frailty index (FI) was calculated as the proportion of 30 possible health deficits. We assessed hypertension, diabetes, obesity, dyslipidemia, sedentarism and smoking as CVRF (determinants) and myocardial infarction, stroke, heart failure as CVD. Poisson regression models adjusted for age, sex, and education was applied to estimate the association between frailty as well as CVRF (independent variables) with CVD (dependent variable). RESULTS: Of the 339 patients, 18,3% were frail (FI ≥ 0.25) and 32.7% had at least one CVD. Both frailty and CVRF were significantly associated with CVD (PR = 1.03, 95% CI 1.01 to 1.05; p = 0.001, and PR = 1.46, 95% 1.24 to 1.71; p < 0.001, respectively) adjusted for covariates. The strength of the association between CVRF and CVD decreased with increasing frailty levels, as indicated by a significant interaction term of frailty and CVRF (p < 0.001). CONCLUSION: Frailty and CVRF are both associated with CVD, but the impact of CVRF decreases in the presence of frailty. When confirmed in longitudinal studies, randomized controlled trials or causal inference methods like Mendelian randomization should be applied to assess whether a shift from traditional CVRF to frailty would improve cardiovascular outcome in the oldest old.

Left ventricular apex to descending aorta valved conduit: description of transthoracic and transesophageal echocardiographic findings in four cases.

Patients with critical aortic stenosis and a "porcelain" aorta are at an increased risk for complications with aortic cross-clamping during valve replacement. To our knowledge, this is the first report of both transthoracic and transesophageal echocardiographic findings of the left ventricle to the descending aorta (LVDA) valved conduit. We present results of four patients in whom this procedure was performed for critical aortic stenosis, who also had a porcelain aorta. "Normal" echo and Doppler findings, along with those of development of a regurgitant valve within the conduit, are presented.

Systemic bacterial invasion induced by sleep deprivation.

Profound sleep disruption in humans is generally believed to cause health impairments. Through comparative research, specific physical effects and underlying mechanisms altered by sleep deprivation are being elucidated. Studies of sleep-deprived animals previously have shown a progressive, chronic negative energy balance and gradual deterioration of health, which culminate in fatal bloodstream infection without an infectious focus. The present study investigated the conditions antecedent to advanced morbidity in sleep-deprived rats by determining the time course and distribution of live microorganisms in body tissues that are normally sterile. The tissues cultured for microbial growth included the blood, four major organs, six regional lymph nodes, the intestine, and the skin. The principal finding was early infection of the mesenteric lymph nodes by bacteria presumably translocated from the intestine and bacterial migration to and transient infection of extraintestinal sites. Presence of pathogenic microorganisms and their toxins in tissues constitutes a septic burden and chronic antigenic challenge for the host. Bacterial translocation and pathogenic sequelae provide mechanisms by which sleep deprivation appears to adversely affect health.

Vein graft failure.

Saphenous vein graft failure is one of the primary reasons for coronary artery bypass reoperation. The economic impact alone in this country is staggering in an era of intensive cost cutting. The fact that some vein grafts remain free of disease for years while the sibling vein develops extensive atherosclerosis remains an enigma. Saphenous vein valves have recently attracted interest. Repeated angiograms show that vein graft disease invariably is accentuated around valves. Studies show that the segment of saphenous vein distal to the valves have more accelerated and intense atherosclerosis. Early results of saphenous vein bypass grafting may be predicted with some degree of certainty by saphenous vein graft biopsy. Attention is now being turned to the hypercoagulable state as a cause of graft failure, as this has not been previously addressed. Research into pharmacologic agents for maintaining open grafts has had disappointing results and aspirin alone is still the single drug of choice to promote patency. Preparation of the graft continues to be important because there is direct evidence that surgical injury during preparation leads to neointimal thickening and vascular smooth muscle proliferation. Although there are some exciting new modalities for preventing graft disease, the difficulty in transposing animal data to humans and the uncertainty of the biologic similarities of in vitro and in vivo endothelial cell biochemistry makes any immediate solution unlikely. Therefore an even greater increase in the use of arterial grafts in the near future seems likely, even with their associated problems.

Functional consequences of sustained sleep deprivation in the rat.

Sleep deprivation disrupts vital biological processes that are necessary for cognitive ability and physical health, but the physiological changes that underlie these outward effects are largely unknown. The purpose of the present studies in the laboratory rat is to prolong sleep deprivation to delineate the pathophysiology and to determine its mediation. In the rat, the course of prolonged sleep deprivation has a syndromic nature and eventuates in a life-threatening state. An early and central symptom of sleep deprivation is a progressive increase in peripheral energy expenditure to nearly double normal levels. An attempt to alleviate this negative energy balance by feeding rats a balanced diet that is high in its efficiency of utilization prolongs survival and attenuates or delays development of malnutrition-like symptoms, indicating that several symptoms can be manipulated to some extent by energy and nutrient consumption. Most changes in neuroendocrine parameters appear to be responses to metabolic demands, such as increased plasma catecholamines indicating sympathetic activation. Plasma total thyroid hormones, however, decline to severely low levels; a metabolic complication that is associated with other sleep deprivation-induced symptoms, such as a decline in body temperature to hypothermic levels despite increased energy expenditure. Metabolic mapping of the brain revealed a dissociation between the energy metabolism of the brain and that of the body. Sleep deprivation's effects on cerebral structures are heterogeneous and unidirectional toward decreased functional activity. The hypometabolic brain structures are concentrated in the hypothalamus, thalamus and limbic systems, whereas few regions in the rest of the brain and none in the medulla, are affected. Correspondence can be found between some of the affected cerebral structures and several of the peripheral symptoms, such as hyperphagia and possible heat retention problems. The factor predisposing to mortality is a decreased resistance to infection. Lethal opportunistic organisms are permitted to infect the bloodstream, which presumably results in a cascade of toxic-like reactions. Host defense is thus the first system to fail. There is neither fever nor marked tissue inflammatory reactions typical of infectious disease states, suggesting that sleep deprivation is immunosuppressive. Each of the four abnormalities identified--(1) a deep negative energy balance and associated malnutrition; (2) heterogeneous decreases in cerebral function; (3) low thyroid hormone concentrations; and (4) decrease resistance to infection--can be viewed as having an early origin during the sleep deprivation process to signify the foremost pathogenic situation to which the other abnormalities might be secondarily related.(ABSTRACT TRUNCATED AT 400 WORDS)

Pituitary and peripheral thyroid hormone responses to thyrotropin-releasing hormone during sustained sleep deprivation in freely moving rats.

Sleep deprivation is associated with poor cognitive ability and impaired physical health, but the ways in which the brain and body become compromised are not understood. In sleep-deprived rats, plasma total T4 and T3 concentrations decline progressively to 78% and 47% below baseline values, respectively, brown adipose tissue 5'-deiodinase type II activity increases 100-fold, and serum TSH values are unknown. The progressive decline in plasma thyroid hormones is associated with a deep negative energy balance despite normal or increased food intake and malnutrition-like symptoms that eventuate in hypothermia and lethal systemic infections. The purpose of the present experiment was to evaluate the probable causes of the low plasma total T4 during sleep deprivation by measuring the free hormone concentration to minimize binding irregularities and by challenging the pituitary-thyroid axis with iv TRH to determine both 1) the pituitary release of TSH and 2) the thyroidal response of free T4 (FT4) and free T3 (FT3) release to the TSH increment. Sleep-deprived rats were awake 91% of the total time compared with 63% of the total time in yoked control rats and 50% of the total time during the baseline period. Cage control comparison rats were permitted to sleep normally. Sustained sleep deprivation resulted in a decline from baseline in plasma FT4 of 73 +/- 6% and FT3 of 45 +/- 12%, which were similar to the declines in total hormone concentrations observed previously; nonstimulated TSH was unchanged. In the yoked and cage control groups, FT4 also declined, but much less than that of the sleep-deprived group. The relative changes in free compared with total hormone concentrations over the study were also less parallel than those in the sleep-deprived group. The plasma TSH response to TRH was similar in all groups across experimental days. The plasma FT4 and FT3 concentrations in sleep-deprived rats increased after TRH-stimulated TSH release to an extent comparable to control values. Taken together, low basal FT4 and FT3 hormone concentrations and unchanged TSH and thyroidal responses to TRH suggest a pituitary or hypothalamic contribution to the hypothyroxinemia during sleep deprivation.

Effects of prolonged sleep deprivation on local rates of cerebral energy metabolism in freely moving rats.

Although sleep deprivation interferes with biological processes essential for performance, health, and longevity, previous studies have failed to reveal any structural or functional changes in brain. We have therefore measured local rates of cerebral glucose utilization (ICMRglc) with the quantitative autoradiographic 2-14C-deoxyglucose method in an effort to determine if and, if so, where sleep deprivation might affect function in sleep-deprived rats. Sleep deprivation was maintained for 11-12 d, long enough to increase whole body energy metabolism, thus confirming that pathophysiological processes that might involve brain functions were evolving. Deep brain temperature was also measured in similarly treated rats and found to be mildly elevated relative to core body temperature. Despite the increased deep brain temperature, systemic hypermetabolism, and sympathetic activation, ICMRglc was not elevated in any of the 60 brain structures examined. Average glucose utilization in the brain as a whole was unchanged in the sleep-deprived rats, but regional decreases were found. The most marked decreases in ICMRglc were in regions of the hypothalamus, thalamus, and limbic system. Mesencephalic and pontine regions were relatively unaffected except for the central gray area. The medulla was entirely normal. The effects of sleep deprivation on brain tended, therefore, to be unidirectional toward decreased energy metabolism, primarily in regions associated with mechanisms of thermoregulation, endocrine regulation, and sleep. Correspondence was found between the hypometabolic brain regions and some aspects of peripheral symptoms.

Sustained sleep deprivation impairs host defense.

Prolonged sleep deprivation in rats causes an unexplained hypercatabolic state, secondary malnutrition symptoms, and mortality. The nature of the vital impairment has long been a mystery. Its determination would help to elucidate the type of organic dysfunction that sleep prevents. There are no gross detectable disturbances in intermediary metabolism, clinical chemistry, or hematological indexes that provide substantial clues to the mediation of sleep-deprivation effects. Furthermore, postmortem examinations reveal no systematic morphological or histopathological findings. Taken together, the cachexia and the absence of evidence of structural damage or organ dysfunction pointed to involvement of a regulatory system that was diffuse, possibly the immune system. Blood cultures revealed invasion by opportunistic microbes to which there was no febrile response. These results suggest that the life-threatening condition of prolonged sleep deprivation is a breakdown of host defense against indigenous and pathogenic microorganisms.

Right gastroepiploic artery used for coronary artery bypass grafting. Evaluation of flow characteristics and size.

Questions remain concerning the physiologic capabilities of the right gastroepiploic artery as a bypass graft in the clinical setting. Our last 90 consecutive pedicle right gastroepiploic artery grafts were prepared with intraluminal papaverine and verapamil. Our series comprised 81 male and 9 female patients with average body surface areas of 1.92 m2. Ages ranged from 11 to 79 years (mean 57.2 years). A second to fourth revascularization was undertaken in 32 patients (35.5%). The following arteries were bypassed: posterior descending artery, 63; right coronary artery, 23; distal right, 4; circumflex, 2; left anterior descending, 1; and diagonal, 1. Free flow rates ranged from 42 to 660 ml/min (mean 179.96 ml/min). Internal diameters measured 1.5 to 4.0 mm (mean 2.20 mm) at the anastomotic sites. Pedicle lengths ranged from 16 to 26 cm (mean 19.2 cm). Inotropic support was required in 11 patients (12%) and had no adverse effects on right gastroepiploic artery grafts. There were 2 hospital deaths (2.2%). Angina has recurred in 6 patients. One patient with cardiomyopathy required transplantation 2 years after coronary bypass grafting. Repeat angiography showed widely patent grafts in 18 patients and generalized narrowing in 4 grafts. In only 2 patients of our total experience has right gastroepiploic artery grafting been aborted because of inadequate conduit size. One right gastroepiploic artery had visible atherosclerosis. This study shows that distal right gastroepiploic artery sizes are comparable with sizes of target coronary arteries. However, neither flow nor size is as consistent when compared with internal thoracic artery grafts. Higher flow rates are related to graft anatomic characteristics and larger body surface areas. Spasm, secondary to harvest in these vasoreactive grafts, can be managed appropriately by intraluminal vasodilating drugs. However, use of the right gastroepiploic artery should be avoided in a setting with possible competition of flow.

Technical advances in the treatment of left ventricular aneurysm.

The resulting abnormal geometry after surgical treatment of left ventricular aneurysm has concerned a number of surgeons since the first successful repair in 1958, but little attention was placed on the altered geometry until attempts were made to effect a more physiologic aneurysmorrhaphy in 1973. Substantial attention was focused on a concept of geometric reconstruction from within the left ventricle in 1985. A prosthetic patch was employed with the concept to redirect normal muscle bundles to their original orientation and position. Further refinements include use of improved materials for the repair, preservation and bypass of the left anterior descending coronary artery, ablation of ventricular arrhythmias when indicated, and the absence of prosthetic material used in contact with the pericardial surface. Our experience with repair of 61 left ventricular aneurysms at West Jefferson Medical Center over a 4 1/2-year period with a 3.3% mortality rate has prompted a change from the standard linear repair to routine use of a modified endoventricular repair. Currently, the low surgical risk due to advances in left ventricular aneurysmorrhaphy combined with the knowledge that contractile areas will progressively deteriorate in ventricles stressed by poor hemodynamics and with data showing improved left ventricular function postoperatively have led to more liberal recommendations for early left ventricular aneurysm repair.

Nutritional and metabolic adaptations to prolonged sleep deprivation in the rat.

To understand how and why sleep deprivation is physically harmful, we explored the possible causal relationship between its two main effects, 1) negative energy balance and 2) a composite of symptoms that resemble protein malnutrition, both of which occur despite increased food consumption. We provided balanced diets augmented with either protein or calories (by increased fat content) to freely moving rats. Interactions between sleep deprivation symptoms and energy and protein supplies were assessed from measurements of body weight regulation, consumption of macronutrients, clinical chemistry and hematology profiles, and physical appearance. The results indicate that sleep deprivation causes malnutrition, which is secondary to increased energy expenditure. Even though food consumption remained normal in sleep-deprived rats fed a diet of high protein-to-calorie ratio, body weight loss was more than 16% of baseline, development of skin lesions was hastened, and longevity was shortened by 40% compared with sleep-deprived rats fed the calorie-augmented diet. Food consumption of the calorie-fed rats was lower during baseline than that of the protein-fed group but during sleep deprivation increased to amounts 250% of normal without net body weight gain. Despite a fat-laden diet the calorie-fed hyperphagic group did not have abnormal levels of plasma cholesterol, triglycerides, or glucose, indicating accelerated turnover of nutrients. As would be consistent with calorie malnutrition, pronounced clinical chemistry or hematological abnormalities were not found in any group. Beneficial effects of the calorie-augmented diet are attributed to 1) caloric density of fat, 2) induction of hyperphagia, and 3) efficiency of utilization of fat. We conclude that diet composition interacts strongly with sleep deprivation, affecting the time course and development of pathologies, whereas it exerted negligible influence on body weight regulation under normal conditions.

The subscapular artery: an alternative conduit for coronary bypass.

The search for an alternative conduit for coronary bypass has prompted our use of the subscapular artery for coronary bypass via a left thoracotomy in three patients. Historically, this artery in conjunction with muscle flaps has been used successfully as a free graft. Its size and length have proved feasible for coronary bypass to the circumflex coronary artery system. All three patients have had excellent clinical results lasting from 6 to 21 months.

Free arterial grafts.

The use of free arterial grafts has increased since the late patency of free internal mammary artery grafts was found to approach that of pedicle internal mammary artery grafts. An intensified search for other suitable arterial grafts has resulted in reports on the use of free gastroepiploic artery grafts and free inferior epigastric artery grafts. Free arterial heterografts and free homograft saphenous veins have had very disappointing results in general. The lateral costal artery, when available, offers another possible arterial conduit in approximately 10% of patients. To effect a wider use of arterial conduits for coronary bypass grafts, a number of techniques have been devised to use the internal mammary artery and other arterial grafts as free grafts.

Atherosclerosis of the ascending aorta and coronary artery bypass. Pathology, clinical correlates, and operative management.

Analysis of 1735 patients who underwent coronary artery bypass grafting from January 1981 through December 1988 revealed 152 (8.8%) patients with mild (4.5%), moderate (2.2%), or severe (2.0%) atherosclerosis of the ascending aorta. Three distinct pathologic patterns were found. The prevalence of stroke in patients with the severe type of aortic disease prompted development of a new operative technique that has been used in 16 patients. It involves a "no-touch" technique of the ascending aorta whereupon the proximal saphenous vein anastomoses are performed end to side to internal mammary artery grafts. Ages ranged from 49 to 80 years (mean 68.9). The 16 patients had 62 distal artery and vein anastomoses and 26 proximal saphenous vein-internal mammary end-to-side anastomoses. Internal mammary artery free flows ranged from 130 to 420 ml/min. Two hospital deaths were unrelated to the technique. There have been no strokes or recurrences of angina. An inordinately high incidence of main left coronary disease (50%), significant carotid disease (79%), and abdominal aortic occlusive or aneurysm disease (93%) was discovered. Ascending aortic atherosclerosis must be suspected in all coronary bypass patients with associated significant carotid, abdominal aortic, and main left coronary artery disease, aortic wall irregularity on ascending aortic angiography, adhesions between the ascending aorta and its adventitia, pale appearance of the ascending aorta, and minimal bleeding of an aortic cannulation stab wound. A "no-touch" technique that avoids any manipulation of the ascending aorta and that uses the internal mammary arteries as the sole source of blood supply for coronary bypass is an effective method to prevent aortic clamp injury, "trash heart," or stroke from severe ascending aortic disease. Preoperative angiographic visualization of the ascending aorta of all patients undergoing coronary artery bypass is mandatory.

Technical considerations for myocardial protection during the course of coronary artery bypass reoperation: the impact of functioning saphenous vein and internal mammary artery grafts.

New technical challenges involving the delivery of cardioplegia during the course of coronary artery bypass operation continue to be presented to the surgeon. Functioning saphenous grafts at reoperation that are at risk for distal embolization, are managed by altering the standard cardioplegia delivery techniques. Management of patent internal mammary artery (IMA) grafts depends upon the status of the native circulation and coronary collateral. The reoperation may be performed with a fibrillating heart, standard cardioplegia with a clamped mammary graft, or cardioplegia delivered during simultaneous circulatory arrest. Myocardial temperature measurements, during the course of more complex operations, are useful in choosing the appropriate technique for myocardial protection.

Technique for use of the inferior epigastric artery as a coronary bypass graft.

A search for a coronary bypass conduit with increased longevity has resulted in harvest of the inferior epigastric artery. The artery is dissected through a paramedian incision with retraction of the rectus muscle to the lateral side. As the inferior epigastric artery courses superiorly, it may lie in one of three positions in relation to the rectus muscle. Distal coronary anastomoses using this conduit are conventional, and the proximal anastomosis may be made to the aorta or end-to-side to an internal mammary artery or venous conduit. After preparation with dilute papaverine-Plasmalyte solution proximal sizes have ranged from 2.5 to 3.25 mm (internal diameter), and distal inferior epigastric artery sizes measured 1.5 to 2.5 mm (internal diameter). The lengths of the conduit ranged from 11.5 to 17.0 cm. Eighteen patients aged 41 to 74 years had inferior epigastric artery grafts to 19 coronary arteries. The indications for use were absent or poor-quality vein, young age with an attempt to limit vein graft, and avoidance of use of bilateral internal mammary artery grafts in insulin-dependent diabetic patients. There was one sterile wound hematoma and one late wound infection. There were no other infections and no deaths. Three patients studied postoperatively revealed widely patent inferior epigastric artery grafts.

Newer surgical techniques in myocardial revascularization.

Recent trends in the patient population coming for surgical treatment of coronary artery disease have prompted alterations in the type of coronary artery bypass surgery performed. Emphasis is placed on the more widespread use of arterial grafts and revascularization of vessels with extensive distal disease, utilizing endarterectomy techniques, in an attempt to provide a more complete and long-lasting revascularization.

Right gastroepiploic artery: a third arterial conduit for coronary artery bypass.

Experience with 39 patients (32 men, 7 women) undergoing coronary artery bypass grafting with the right gastroepiploic artery (RGEA) is reported. Indications initially included poor-quality or absent saphenous vein, ascending aortic atherosclerosis, and repeat coronary artery bypass grafting. The average number of grafts per patient was 4.10. Arteries bypassed were the posterior descending (22 patients), right coronary (12), diagonal (5), and marginal (4). Distal RGEA internal diameters of all grafts measured 1.5 to 3.25 mm (average diameter, 2.14 mm). Pedicled graft lengths measured 18 to 30 cm (average length, 23.7 cm), and free grafts, 8 to 24 cm (average length, 17.7 cm). In 6 patients, no vein grafts were used, and in all patients, at least one internal mammary artery graft was placed. Early postoperative cardiac catheterization (19 pedicled and ten free grafts) in 29 patients revealed all grafts to be patent without a kink or twist, but three of these free RGEA grafts had vasospasm. Advantages of RGEA grafts are as follows: (1) it is a third arterial conduit with artery-artery anastomoses of comparable sizes; (2) a shorter leg incision or no leg incision is necessary; (3) it can be harvested simultaneously with the internal mammary artery and the saphenous vein; (4) the proximal anastomosis (free grafts) is easy; (5) its use avoids bilateral internal mammary artery grafts in patients at high risk for sternal infection; and (6) atherosclerotic ascending aortas are not clamped. Subintimal hyperplasia and atherosclerosis of RGEA grafts are unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)