Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low-28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low–28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

Effect of ivabradine-induced heart rate reduction on flow-mediated dilation measured with high-sensitivity ultrasound in patients with stable coronary heart disease

Background

Experimental data suggests that exclusive heart rate reduction with ivabradine is associated with the amelioration of the endothelial function. Since it is presently unknown whether this also applies to humans, the aim of this pilot study was to investigate whether heart rate reduction with ivabradine modulates the endothelial function in humans with an established coronary heart disease.

Methods

Using high-sensitivity ultrasound, we analysed the flow-mediated (FMD) and nitro-mediated dilation (NMD) of the brachial artery in 25 patients (62.9?±?8.4 years) with a stable coronary heart disease and a resting heart rate of ≥70 beats per minute (bpm). To assess acute effects, measurements were performed before and 4 hours after the first intake of ivabradine 7.5 mg. Sustained effects of an ivabradine therapy (5 mg to 7.5 mg twice daily) were investigated after 4 weeks.

Results

We found a significant decrease in heart rate, both 4 hours after the intake of 7.5 mg of ivabradine (median -8 [interquartile range (IQR) -14 to -4] bpm) and after 4 weeks of twice daily intake (median -10 [IQR-17 to -5] bpm) (p?<?0.05). However, the FMD did not change significantly: neither after first dose of ivabradine nor after sustained therapy (baseline FMD: median 5.0 [IQR 2.4 to 7.9]%; FMD 4 hours after 7.5 mg of ivabradine: median 4.9 [IQR 2.7 to 9.8]%; FMD after 4 weeks of ivabradine therapy: median 6.1 [IQR 4.3 to 8.2]%). No significant changes of the NMD were observed. In regression analysis, the heart rate and FMD did not correlated, irrespective of the ivabradine intake (r²?=?0.086).

Conclusion

In conclusion, in our study heart rate reduction through ivabradine does not improve the endothelial function in patients with a stable coronary heart disease. Moreover, we found no correlation between the heart rate and the endothelial function.     

Effects of exercise training on coronary collateralization and control of collateral resistance

Coronary collateral vessels serve as a natural protective mechanism to provide coronary flow to ischemic myocardium secondary to critical coronary artery stenosis. The innate collateral circulation of the normal human heart is typically minimal and considerable variability occurs in extent of collateralization in coronary artery disease patients. A well-developed collateral circulation has been documented to exert protective effects upon myocardial perfusion, contractile function, infarct size, and electrocardiographic abnormalities. Thus therapeutic augmentation of collateral vessel development and/or functional adaptations in collateral and collateral-dependent arteries to reduce resistance into the ischemic myocardium represent a desirable goal in the management of coronary artery disease. Tremendous evidence has provided documentation for the therapeutic benefits of exercise training programs in patients with coronary artery disease (and collateralization); mechanisms that underlie these benefits are numerous and multifaceted, and currently under investigation in multiple laboratories worldwide. The role of enhanced collateralization as a major beneficial contributor has not been fully resolved. This topical review highlights literature that examines the effects of exercise training on collateralization in the diseased heart, as well as effects of exercise training on vascular endothelial and smooth muscle control of regional coronary tone in the collateralized heart. Future directions for research in this area involve further delineation of cellular/molecular mechanisms involved in effects of exercise training on collateralized myocardium, as well as development of novel therapies based on emerging concepts regarding exercise training and coronary artery disease.     

New Trends in the Treatment of Angina Pectoris

Traditionally when considering the pharmacologic basis of therapy in angina pectoris, attention is focussed on alterations of coronary blood flow. Yet the diseased coronary arteries in these patients often do not appear to be capable of responding to vasodilatory drugs. Since the pain of myocardial ischemia is relieved by a number of interventions without an increase in coronary blood flow, the concept herein considered is that angina pector is best viewed as an unfavorable relation between myocardial oxygen requirements and availability. Thus, the clinical value of the major antianginal agents is thought to be based importantly upon their actions to reduce myocardial oxygen consumption rather than to increase coronary blood flow.Sublingual nitroglycerin possesses a powerful dilator effect on veins which reduces venous return and thereby the size of the heart and intra-myocardial tension; thus myocardial oxygen requirements are diminished.The beta-adrenergic receptor blocking drug, propranolol (Inderal®), inhibits sympathetic stimulation of the heart at rest and during exercise. Thus, myocardial oxygen requirements are diminished by the reduction in heart rate and diminished contractility. As a result of this latter action, cardiac output is reduced and thereby arterial pressure and intramyocardial tension is lowered. In patients with advanced heart disease and borderline cardiac compensation, propranolol is hazardous because it removes the availability of one of the important reserve mechanisms for maintaining cardiac compensation—the sympathetic support of the failing heart.The introduction of electrical stimulation of the carotid sinus nerves as a means of therapy in patients with angina pectoris has provided a powerful tool for the treatment of patients with refractory ischemic pain.     

Vasculogenesis and angiogenesis: Extracellular matrix remodeling in coronary collateral arteries and the ischemic heart

Heart failure secondary to ischemic cardiomyopathy is the primary cause of cardiovascular mortality. The promise of the collateral circulation lies in its potential to alter the course of the natural history of coronary heart disease. The collateral circulation of the heart is responsible for supplying blood and oxygen to the myocardium at ischemic risk following severe stenosis and reduced vasoelasticity function of a major coronary artery. In response to flow, stress, and pressure, collateral vessels are restructured and remodeled. Vascular remodeling by its very nature implies synthesis and degradation of extracellular matrix components in the vessel wall. Under normal physiological conditions proteinases that break down the specialized matrix are tightly regulated by antiproteinases. The balance between proteinase and antiproteinase influences is discoordinated during collateral development which leads to adaptive changes in the structure, function, and regulation of extracellular matrix components in the vessel wall. The role of extracellular matrix components in coronary collateral vessel formation in a canine model of chronic coronary artery occlusion has been demonstrated. The role of matrix proteinases and antiproteinases in the collateral vessel play a significant role in the underlying mechanisms of collateral development. This review presents new and significant information regarding the role of extracellular matrix proteinases and antiproteinases in vascular remodeling, function, and collateral development. Such information will have a significant impact on the understanding of the basic biology of the vascular extracellular matrix turnover, remodeling, and function as well as on elucidating potential avenues for pharmacological approaches designed to increase collateral formation and optimize myocardial blood flow in the treatment of ischemic heart disease. J. Cell. Biochem. 65:388–394. © 1997 Wiley-Liss, Inc.     

Cell-based cardiovascular repair and regeneration in acute myocardial infarction and chronic ischemic cardiomyopathy-current status and future developments

Ischemic heart disease is the main cause of death and morbidity in most industrialized countries. Stem- and progenitor cell-based treatment approaches for ischemic heart disease are therefore an important frontier in cardiovascular and regenerative medicine. Experimental studies have shown that bone-marrow-derived stem cells and endothelial progenitor cells can improve cardiac function after myocardial infarction, clinical phase I and II studies were rapidly initiated to translate this concept into the clinical setting. However, as of now the effects of stem/progenitor cell administration on cardiac function in the clinical setting have not met expectations. Thus, a better understanding of causes of the current limitations of cell-based therapies is urgently required. Importantly, the number and function of endothelial progenitor cells is reduced in patients with cardiovascular risk factors and/or coronary artery disease. These observations may provide opportunities for an optimization of cell-based treatment approaches. This review provides a summary of current evidence for the role and potential of stem and progenitor cells in the pathophysiology and treatment of ischemic heart disease, including the properties, and repair and regenerative capacities of various stem and progenitor cell populations. In addition, we describe modes of stem/progenitor cell delivery, modulation of their homing as well as potential approaches to "prime" stem/progenitor cells for cardiovascular cell-based therapies.     

Coronary flow reserve in stress-echo lab. From pathophysiologic toy to diagnostic tool

Background

High-rate pacing is a valid stress test to be used in conjunction with echocardiography; it is independent of physical exercise and does not require drug administration. There are two main applications of pacing stress in the echo lab: the noninvasive detection of coronary artery disease through induction of a regional transient dysfunction; and the assessment of contractile reserve through peak systolic pressure/end-systolic volume relationship at increasing heart rates to assess global left ventricular contractility.

Methods

The pathophysiologic rationale of pacing stress for noninvasive detection of coronary artery disease is obvious, with the stress determined by a controlled increase in heart rate, which is a major determinant of myocardial oxygen demand, and thereby tachycardia may exceed a fixed coronary flow reserve in the presence of hemodynamically significant coronary artery disease. The use of pacing stress echo to assess left ventricular contractile reserve is less established, but promising. Positive inotropic interventions are mirrored by smaller end-systolic volumes and higher end-systolic pressures. An increased heart rate progressively increases the force of ventricular contraction (Bowditch treppe or staircase phenomenon). To build the force-frequency relationship, the force is determined at different heart rate steps as the ratio of the systolic pressure (cuff sphygmomanometer)/end-systolic volume index (biplane Simpson rule). The heart rate is determined from ECG.

Conclusion

Two-dimensional echocardiography during pacing is a useful tool in the detection of coronary artery disease. Because of its safety and ease of repeatability noninvasive pacing stress echo can be the first-line stress test in patients with permanent pacemaker. The force-frequency can be defined as up- sloping (normal) when the peak stress pacing systolic pressure/end-systolic volume index is higher than baseline and intermediate stress values, biphasic with an initial up- sloping followed by a later down-sloping trend, or flat or negative when peak stress pacing systolic pressure/end-systolic volume index is equal or lower than baseline stress values. This approach is certainly highly feasible and allows a conceptually immaculate definition of contractility with prognostic usefulness, but its therapeutic implications remains to be established. Bowditch treppe, assessed with pacing stress, can be used to assess the optimal stimulation frequency and to optimise the patient's chronotropic response in programming rate-adaptive pacemakers.     

多种无创检查组合在冠心病诊断中的价值

目的：评价多种无创辅助检查组合对冠状动脉粥样硬化性心脏病（冠心病）辅助诊断价值,筛选有效的冠心病确诊和排除指标,初步确定优化的冠心病早期诊断策略。方法：回顾性分析6419例冠心病患者多项无创辅助检查结果（包括静息心电图、24小时动态心电图、负荷心电图、负荷核素心肌显像、16或64排CT冠状动脉成像）,以冠状动脉造影阳性（至少一支主要冠状动脉或其主要分支的内径有≥50％的狭窄）为金标准,观察各种无创辅助检查组合对冠心病诊断的特异性、敏感性、误诊率、漏诊率、阳性预测值和阴性预测值。结果：多项无创辅助检查组合在冠心病的诊断中敏感性56．02-87．43％,特异36．13-87．61％,阳性预测值58．83．97．16％,阴性预测值30．21．73．36％,非介入手段中,敏感性和阴性预测值以动态心电图联合核素心肌灌注显像组最高,特异性和阳性预测值以动态心电图联合冠脉CT成像组最高。结论：辅助检查组合可作为无创性诊断、评价冠心病的重要方法,动态心电图可作为各级别医院冠心病筛查的基本及重要手段。     

Effect of malate and NAD on local myocardial contraction during acute coronary occlusion

In acute experiments on cats the effects of malate (100 mg/kg), NAD (0.2 mg/kg) and their combination on regional myocardial contractility were studied during acute coronary artery occlusion. All the drugs increased significantly myocardial contractility in border and intact zones. However, the response of the central ischemic zone to drug effects was insignificant.     

MYOCARDIAL INFARCTION FOLLOWING CAROTID ENDARTERECTOMY

Myocardial infarction has been the major cause of mortality following operation for cerebrovascular insufficiency. In our institution, a clinical diagnosis of coronary artery disease was made in 37 of 125 (29.6%) consecutive male patients having carotid endarterectomy. Six of these 37 patients developed postoperative myocardial infarction. In contrast, none of the 88 patients without coronary artery disease developed myocardial infarction. A more recently treated group of 20 patients who had undergone carotid artery surgery and had previously undergone coronary artery bypass for angina did not develop postoperative myocardial infarction. These data suggest that in patients with both coronary artery and carotid artery disease, prior or concomitant coronary artery bypass should be considered. Myocardial infarction has been the leading cause of early and late death following operation for cerebrovascular insufficiency.(1) DeBakey(2) found operative mortality in patients having surgery for cerebrovascular insufficiency directly related to the incidence of coronary artery disease. An increased operative mortality due to reinfarction has been found in patients recovering from recent myocardial infarction.(3) Cooley(4) found that in patients having aortocoronary bypass there was no increased operative mortality 30 days after myocardial infarction and this may apply to patients having carotid endarterectomy. Subendocardial postoperative infarction associated with minor T wave changes and slight enzyme elevation had a better prognosis than did transmural infarction causing significant Q waves, sequential ST and T wave changes and marked enzyme elevations.(5) The purpose of this study was to document our experience with myocardial infarction in patients undergoing carotid artery operation for clinical coronary artery disease. Consideration of the role of saphenous vein bypass in those patients with coronary artery disease was the background for this review even though the evidence that myocardial infarction can be prevented with saphenous vein bypass operation is only preliminary at the present time.(6)     

Behavioural prevention of ischemic heart disease.

Heart disease continues to be a major cause of disablement and death in Canada. Elevated serum cholesterol concentrations, hypertension and cigarette smoking are among the standard risk factors associated with ischemic heart disease. Research attention has also been directed at the role of behavioural factors in the development of atherosclerosis and myocardial infarction. Experimental findings support a conceptual approach to the interplay of psychologic stress, the type A "coronary"-prone behaviour pattern and pathophysiologic mechanisms that have been implicated in the development of coronary artery disease. It is concluded that type A behaviour and stress contribute substantially to the pathogenesis of cardiovascular disease. However, assessment of the manner in which these two variables influence the pathophysiology of ischemic heart disease requires further research, with systematic examination of physiologic and biochemical processes. Potential strategies for modifying type A behaviour are reviewed. However, unequivocal support for the preventive efficacy of behavioural approaches must await future research.     

Statins enhance clonal growth of late outgrowth endothelial progenitors and increase myocardial capillary density in the chronically ischemic heart

Background

Coronary artery disease and ischemic heart disease are leading causes of heart failure and death. Reduced blood flow to heart tissue leads to decreased heart function and symptoms of heart failure. Therapies to improve heart function in chronic coronary artery disease are important to identify. HMG-CoA reductase inhibitors (statins) are an important therapy for prevention of coronary artery disease, but also have non-cholesterol lowering effects. Our prior work showed that pravastatin improves contractile function in the chronically ischemic heart in pigs. Endothelial progenitor cells are a potential source of new blood vessels in ischemic tissues. While statins are known to increase the number of early outgrowth endothelial progenitor cells, their effects on late outgrowth endothelial progenitor cells (LOEPCs) and capillary density in ischemic heart tissue are not known. We hypothesized that statins exert positive effects on the mobilization and growth of late outgrowth EPCs, and capillary density in ischemic heart tissue.

Methodology/Principal Findings

We determined the effects of statins on the mobilization and growth of late outgrowth endothelial progenitor cells from pigs. We also determined the density of capillaries in myocardial tissue in pigs with chronic myocardial ischemia with or without treatment with pravastatin. Pravastatin therapy resulted in greater than two-fold increase in CD31+ LOEPCs versus untreated animals. Addition of pravastatin or simvastatin to blood mononuclear cells increased the number of LOEPCs greater than three fold in culture. Finally, in animals with chronic myocardial ischemia, pravastatin increased capillary density 46%.

Conclusions

Statins promote the derivation, mobilization, and clonal growth of LOEPCs. Pravastatin therapy in vivo increases myocardial capillary density in chronically ischemic myocardium, providing an in vivo correlate for the effects of statins on LOEPC growth in vitro. Our findings provide evidence that statin therapy can increase the density of capillaries in the chronically ischemic heart.     

Isolation and characterization of cytosolic alanine aminotransferase isoforms from starved rat liver

Despite significant advances in myocardial revascularization and reperfusion, coronary artery disease and subsequently myocardial infarction, are the leading causes of morbidity and mortality in the United States. Strategies which improve the myocardial substrate during and following a myocardial infarction-such as the regrowth of functional blood vessels to the ischemic myocardium would be of great clinical importance. This review article attempts to address this important clinical issue through identifying potential signalling mechanisms by various mode of preconditioning that cause angiogenesis.     

Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling

The aim of this study was to investigate the effect of chronic heart rate (HR) reduction with the hyperpolarization-activated current inhibitor ivabradine on the global phenotype of left ventricular (LV) remodeling in a ligated rat model. Seven days after coronary artery ligation, Wistar rats received ivabradine (10 mg · kg(-1) · day(-1) administered in drinking water) [myocardial infarction + ivabradine (MI+IVA), n = 22] or vehicle only (drinking water) (MI, n = 20) for 90 days. A sham group (n = 20) was included for model validation. MI+IVA rats had 12% lower HR (P < 0.01), improved LV volumes, 15% higher LV ejection fraction (LVEF, P < 0.01) than MI rats, and 33% reductions in both plasma atrial natriuretic peptide (ANP, P = 0.052) and cardiac hydroxyproline. Using patch-clamp, action potential duration was reduced and transient outward current density increased (P < 0.05). Cardiac energy metabolism was also improved (+33% creatine phosphate, P < 0.001; +15% ATP; and +9% energy charge, P < 0.05). Significant correlations were found between HR and parameters of cardiac metabolism, ANP, and LVEF (all P < 0.05). The HR-reducing properties of ivabradine prevent changes in the global phenotype of LV remodeling in the rat, optimize energy consumption, and avoid electrophysiological and structural remodeling.     

Therapeutic potential of vitamin E against myocardial ischemic-reperfusion injury.

Myocardial ischemia is a disease process characterized by reduced coronary flow such that the supply of nutritive blood to heart muscle (myocardium) is insufficient for normal myocardial aerobic metabolism. Prompt reestablishment of coronary flow by invasive and noninvasive clinical procedures is the most direct and effective means of limiting myocardial damage in ischemic heart disease patients, although reperfusion carries with it an injury component which may reflect, at least to some degree, the toxic effects of partially reduced oxygen species and their participation in degenerative cellular processes such as membrane lipid peroxidation. Vitamin E, a lipophilic, chain-breaking antioxidant, is a prominent membrane constituent in heart muscle, where it modulates/regulates various aspects of heart muscle-cell metabolism and function. Vitamin E's beneficial effects against experimentally induced oxidative damage to the heart, along with inverse epidemiological correlations between plasma vitamin E level and either anginal pain or mortality due to ischemic heart disease, suggest that vitamin E might have protective and therapeutic roles against myocardial ischemic-reperfusion injury. Laboratory investigations aimed at addressing this possibility have demonstrated that vitamin E supplementation protects isolated hearts against ischemic-reperfusion injury, and relatively more inconsistent and limited data document cardioprotective effects of vitamin E in some animal models of myocardial ischemia-reperfusion, especially when administered prior to the ischemic period. Clinical attempts to establish whether vitamin E has therapeutic benefit in ischemic heart disease patients remain inconclusive, having relied upon a variety of nonuniformly controlled protocols and a single, rather subjective endpoint (anginal pain). Consequently, although laboratory data constitute a conceptual context for and indirect support of the idea that vitamin E could be a cardioprotectant against ischemic-reperfusion injury, compelling clinical evidence regarding vitamin E's therapeutic potential in the ischemic heart-disease patient is lacking. Elective coronary revascularization would appear to provide an attractive clinical setting for evaluating the therapeutic efficacy of vitamin E in the context of cardiac ischemia-reperfusion. Further biochemical work would still be required to define how vitamin E exerts any cardioprotective effect observed in these patients.     

Apport de l’IRM cardiaque à l’exploration des cardiopathies ischémiques

This article presents the current and future possibilities of the cardiac magnetic resonance imaging (MRI) in the ischemic heart disease. It is not an emergency technique, but is becoming an element of decision for an acute myocardial infarction. It makes it possible to visualize the extent of the myocardial lesions in post acute infarction, to appreciate functional recovery and to uncover a nonsymptomatic coronary stenosis or of atypical clinical presentation. The visualization of the coronary arteries in MRI is realizable, but remains experimentation field. The cardiac MRI place is to be defined by each medical team according to their diagram of ischemic heart disease follow-up.     

A new technique of coronary artery ligation: Experimental myocardial infarction in rats in vivo with reduced mortality

In vivo models of myocardial infarction following coronary artery ligation in the rat still suffer from high early mortality and a low rate of success of myocardial infarction. This study investigated the possibility of reducing early mortality and increasing the rate of myocardial infarction by modifications of surgical techniques. Eighteen rats were divided into two groups: normal control (3 rats) and ligation (15 rats). The major modifications of surgical techniques used in this study include: (1) no exteriorization of the heart, (2) ligation of the origins of the branches rather than the main trunk of the left coronary artery, (3) removal of air from the chest after closure, (4) supplying oxygen immediately after extubation. Following surgery, the rats recovered uneventfully and 11 rats were alive after 16 weeks. One rat, with a large myocardial infarction, died 2 h after surgery. Early mortality (during surgery and 1 week after surgery) was 6.7% with a success rate of myocardial infarction of 85%. The left ventricle in the ligation group showed significant dilation relative to normal and shamoperated control hearts (317% of control hearts, p < 0.001). However, myocardial mass did not increase. The average infarct size was 33%. These results demonstrate that a reduction in early mortality and an increased success rate of myocardial infarction can be achieved by modifications of surgical techniques.     

Sex matters: secular and geographical trends in sex differences in coronary heart disease mortality

ObjectiveTo examine secular trends and geographical variations in sex differences in mortality from coronary heart disease and investigate how these relate to distributions in risk factors.Design National and international data were used to examine secular trends and geographical variations in sex differences in mortality from coronary heart disease and risk factors.SettingEngland and Wales, 1921-98; Australia, France, Japan, Sweden, and the United States, 1947-97; 50 countries, 1992-6.ResultsThe 20th century epidemic of coronary heart disease affected only men in most industrialised countries and had a very rapid onset in England and Wales, which has been examined in detail. If this male only epidemic had not occurred there would have been 1.2 million fewer deaths from coronary heart disease in men in England and Wales over the past 50 years. Secular trends in mean per capita fat consumption show a similar pattern to secular trends in coronary heart disease mortality in men. Fat consumption is positively correlated with coronary heart disease mortality in men (r_s=0.79; 95% confidence interval 0.70 to 0.86) and inversely associated with coronary heart disease mortality in women (−0.30; −0.49 to −0.08) over this time. Although sex ratios for mortality from coronary heart disease show a clear period effect, those for lung cancer show a cohort effect. Sex ratios for stroke mortality were constant and close to unity for the entire period. Geographical variations in the sex ratio for coronary heart disease were associated with mean per capita fat consumption (0.64; 0.44 to 0.78) but were not associated with the sex ratio for smoking.ConclusionSex differences are largely the result of environmental factors and hence not inevitable. Understanding the factors that determine sex differences has important implications for public health, particularly for countries and parts of countries where the death rates for coronary heart disease are currently increasing.

What is already known on this topic

Mortality for coronary heart disease is greater in men than women in most industrialised countriesThe most widely accepted explanation for this difference is that women are protected by oestrogen

What this study adds

The sex difference in mortality from coronary heart disease varies over time and between countries in a way that cannot be explained by endogenous oestrogenThese trends indicate that sex differences in mortality from coronary heart disease are driven primarily by environmental factorsSex differences in coronary heart disease are not inevitableUnderstanding more about the factors that cause the sex differences in mortality from coronary heart disease has important public health implications     

Prevention of disorders of the electric stability of the heart in experimental infarct using adaptation to hypoxia

It has been shown on rats preadapted to hypoxia in an altitude chamber that myocardial infarction induced by ligation of the coronary artery was accompanied by less disturbances in the electrical stability of the heart, namely by a twofold decrease in ventricular fibrillation threshold and a considerable decrease in the heart ectopic activity. Preliminary adaptation provided the maintenance of myocardial contractility in infarction.