Heart rate as a cardiovascular risk factor: do women differ from men?

Considerable progress has been made in our understanding of the role of high heart rate in determining cardiovascular morbidity and mortality. However, whether the association between fast heart rate and cardiovascular disease is equally strong in males and females is still a matter for debate. In most studies, the predictive value of tachycardia for all-cause mortality has been found to be weaker in women than in men, and in some studies no association between heart rate and cardiovascular mortality was observed. In particular, high heart rate appeared to be a weak predictor of death from coronary heart disease in the female gender. Multiple mechanisms by which sympathetic overactivity could cause hypertension and the metabolic syndrome of insulin resistance have been documented. Recent results obtained at the Ann Arbor laboratory from the analysis of four populations indicate that these mechanisms are operative mostly in males in whom tachycardia reflects a heightened sympathetic tone. In women, fast heart rate would merely represent the extreme of a normal distribution. However, tachycardia can also have a direct impact on the arterial wall, as demonstrated in laboratory studies, and can favour the occurrence of cardiac arrhythmias. The impact of these mechanisms may be similar in men and women and could explain why a high heart rate has been found to have a detrimental effect also in the female gender. Pharmacological reduction of high heart rate is an additional desirable goal of therapy in several clinical conditions such as hypertension, myocardial infarction and congestive heart failure. Although a greater effect is expected in men, cardiac slowing could counteract the detrimental haemodynamic effect of tachycardia also in women.     

Gender-related differences in the sympathetic vasoconstrictor drive of normal subjects

The risk of cardiovascular disease has been linked to sympathetic activation and its incidence is known to be lower in women than in men. However, the effect of gender on the sympathetic vasoconstrictor drive has not yet been established. In the present study, we investigated whether there is a gender difference in MSNA (muscle sympathetic nerve activity) and blood flow, and to determine the mechanisms involved. We examined 68 normal subjects, 34 women and 34 men, matched for age, BMI (body mass index) and waist circumference. MSNA was measured as the mean frequency of single units (s-MSNA) and as multi-unit bursts (m-MSNA) from the peroneal nerve simultaneously with its supplied muscle CBF (calf blood flow). Women had lower (P=0.0007) s-MSNA (24+/-2.0 impulses/100 cardiac beats) than men (34+/-2.3 impulses/100 cardiac beats), and a greater baroreceptor reflex sensitivity controlling efferent sympathetic nerve activity than men. The sympathetic activity was inversely and directly correlated respectively, with CBF (P=0.03) and CVR (calf vascular resistance; P=0.01) in men only. The responses of an increase in CVR to cold pressor and isometric handgrip tests were significantly smaller in women (P=0.002) than in men, despite similar increases in efferent sympathetic nerve activity. Women had a lower central sympathetic neural output to the periphery, the mechanism of which involved differences in central and reflex control, as well as a lower vasoconstrictor response to this neural output. It is suggested that this may partly explain the observed lower incidence of cardiovascular events in women compared with men.     

Diabetic cardiac autonomic neuropathy and anesthetic management: review of the literature

Cardiac autonomic neuropathy is a serious complication among diabetic patients. It occurs in both type 1 and type 2 diabetes, and its progression results in poor prognosis and increased mortality. During its course, parasympathetic and sympathetic nerve fibers of the cardiovascular system are damaged, resulting in potentially serious cardiac complications and even death. Poor glycemic control is believed to play a pivotal role in the pathogenesis of cardiac autonomic neuropathy. Its underlying etiology is not well understood; however, several potential pathologic mechanisms have been identified. Several clinical manifestations of cardiac autonomic neuropathy have been reported, including resting tachycardia, exercise intolerance, loss of heart rate variability, orthostatic hypotension, prolonged QT interval, silent ischemia, and sudden death. Diabetic patients exhibiting these signs and symptoms are at greater risk of anesthesia-related complications. A series of noninvasive autonomic tests were developed for the diagnosis of cardiac autonomic neuropathy, improving the management of diabetic patients requiring general anesthesia. These patients often experience cardiovascular events that may increase perioperative morbidity and mortality. The presence of cardiac autonomic neuropathy alters the hemodynamic response to induction and tracheal intubation during general anesthesia, resulting in intraoperative hypotension. A thorough preoperative assessment and vigilant monitoring perioperatively ensure successful anesthesia management.     

Cardiac sympathovagal balance during sleep apnea episodes

Summary. The main acute cardiovascular effects of obstructive sleep apnea syndrome (OSAS) are elevation of blood pressure and reflectory bradycardia, which are followed by an abrupt tachycardia on resumption of breathing. This haemodynamic instability is related to hypoxemia and arousal, and may lead to increased risk from cardiac arrhythmias and sudden cardiac death, as well as to the development of chronic arterial hypertension, in these patients. The aim of this study was to apply frequency domain analysis of heart rate variability (HRV) measured from continuous electrocardiogram (ECG) recordings to evaluate how cardiac autonomic function, and especially cardiac sympathovagal tone, changes during sleep apnea episodes. We identified 41 apneas leading to more than 4%-unit arterial oxygen desaturation in 12 patients (11 men, 1 women, age range 27–67 years). Frequency domain analysis of HRV was performed from ECG recordings using 4 min epochs starting 20 min before apnea began and lasting 20 min after the beginning of apnea. The mean (± SEM) fall in oxygen saturation during the apnea was 6.8±0.6%-units. While high frequency band (HF, reflects cardiac vagal activity) remained unchanged, low frequency band (LF, mainly sympathetic activity) showed a constant increase, leading to significant change in the sympathovagal balance (LF/HF ratio). In conclusion, concordantly with previous peripheral sympathetic-nerve recordings, frequency domain analysis of HRV is able to detect sympathetic activation during sleep apnea episodes, leading to marked change in the sympathovagal balance.     

Diabetes,heart rate,and mortality

A large body of evidence indicates that a persistently high heart rate is associated with a significant risk for higher mortality and sudden death in individuals with a variety cardiovascular disorders, as well as in the general population. Heart rates elevated beyond a certain threshold have been found to be a risk factor for mortality in patients with hypertension, in survivors of myocardial infarction, and in patients with impaired cardiac function. Conversely, a naturally slow heart rate, or one that is slow by virtue of sympathetic blockade induced by pharmacologic agents, may result in longer survival. This is particularly evident in the case of beta-adrenergic blocking drugs, especially in patients after myocardial infarction and in those with acute as well as chronic cardiac failure, a syndrome in which there is a complex neurohormonal disturbance with elevated heart rate. Persistently elevated heart rate is also a feature of diabetes mellitus associated with autonomic neuropathy. Whether this also constitutes an independent risk factor for sudden and augmented mortality is not well defined. In this review, the data on the role of increased heart rate as a risk factor for mortality are examined in the context of other factors that may have therapeutic implications.     

Influence of gender on the sympathetic neural adjustments to alterations in systemic oxygen levels in humans

The purpose of this investigation was to determine whether gender influences the muscle sympathetic nerve activity (MSA) and systemic cardiovascular adjustments to alterations in systemic oxygen levels. To accomplish this, we performed direct (intraneural) measurements of muscle sympathetic nerve activity in 11 male and seven female young healthy adults during room air breathing, moderate isocapnic hypoxaemia and hyperoxaemia. During hypoxaemia, arterial oxygen saturation declined similarly in men and women. The magnitudes of the peak increases in MSA and stimulus–response `gain' were not different between groups. However, the women had a shorter latency of response (P<0·05). Women also demonstrated a greater increase in heart rate and a modest elevation in diastolic blood pressure, whereas the ventilatory responses were identical in the two groups. During normoxic recovery, MSA returned to baseline more quickly in women than in men (P<0·05). During hyperoxaemia, muscle sympathetic nerve activity decreased only in the men (P<0·05). Heart rate decreased slightly (P<0·05) in both men and women, whereas blood pressure and minute ventilation were unchanged from normoxic control levels. Our findings fail to support an effect of gender on the peak muscle sympathetic nerve activity response to moderate isocapnic hypoxaemia in healthy young adult humans, although women demonstrate a shorter latency for sympathoexcitation and recovery under these conditions. In response to hyperoxaemia, women fail to demonstrate the sympathoinhibition consistently observed in men, possibly because of the low resting levels of MSA characteristic of young adult women. Thus, gender appears to contribute to the interindividual variability in sympathetic and cardiovascular responses to alterations in systemic oxygen levels.     

Predominance of postsynaptic mechanism in vagal suppression of sympathetic tachycardia in the dog

The amplitude of reduction in heart rate induced by vagal stimulation is greater when the background level of sympathetic tone is increased (accentuated antagonism). Both pre- and postsynaptic muscarinic mechanisms have been proposed to account for this phenomenon. We attempted to clarify the relative importance of each mechanism by comparing the magnitude of vagal bradycardia during neurally induced tachycardia with that during nonneurally induced tachycardia in the anesthetized dog. Graded tachycardia was induced by raising the stimulus frequency of cardiac sympathetic nerve stimulation stepwise from 1 to 3 and 5 and 10 Hz, and it was also induced by norepinephrine infusion (0.3-10 micrograms/min into the right coronary artery), isoproterenol infusion (0.1 and 0.3 micrograms/kg/min i.v.) and glucagon injection (3-30 micrograms/kg i.v.). The magnitude of the bradycardia produced by vagal nerve stimulation at 3 Hz was determined during the resting state and during the tachycardic state produced by cardiac nerve stimulation and by drug administration. The magnitude of vagal bradycardia was greater during tachycardic state than during the resting state regardless of the means through which tachycardia was produced. Vagal bradycardia during norepinephrine or isoproterenol infusion was of the same magnitude as that during the cardiac sympathetic nerve stimulation when they were compared at the same heart rate. Vagal bradycardia during the glucagon-induced tachycardia was greater than that which occurred during sympathetic tachycardia. Temporary bradycardia resulting from a single-pulse vagal nerve stimulation was augmented markedly during the cardiac sympathetic nerve stimulation, whereas a 2-sec interruption of the cardiac sympathetic nerve stimulation did not alter the sustained tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)     

The changing face of sympathetic overactivity in hypertension

There is a lot of evidence showing that sympathetic activity is increased in a large proportion of patients with hypertension. However, the clinical impact of this state is frequently underestimated. Several factors seem to be misunderstood, such as whether sympathetic overactivity is reproducibly present, whether it lasts throughout 24 h, and what is the significance of its association with tachycardia. In this review, we present data to indicate that several haemodynamic changes in hypertension such as elevated cardiac output and heart rate and alteration in vascular resistance are neurogenic. The relationship between the increased sympathetic tone and decreased parasympathetic tone in hypertension is reciprocal, which strongly suggests that the abnormality emanates from the brain. The increase in sympathetic drive in hypertension is widespread across many organs. Beside the heart it is seen in the kidney and skeletal muscle, and even in platelets. We also discuss the possible mechanisms of the haemodynamic transition from this hyperkinetic state to established hypertension. We propose a hypothesis where down-regulation of beta-adrenergic responsiveness plays a major role in explaining the haemodynamic changes as well as metabolic alterations, such as hyperinsulinaemia and even the gain of weight in hypertension. Thus, the increased sympathetic tone may be involved in the genesis of multiple, pressure-independent coronary risk factors in hypertension.     

Heart rate in ischemic heart disease. The innovation of ivabradine: More than pure heart rate reduction

A wealth of data suggests that heart rate (HR) is an independent predictor of cardiovascular and all-cause mortality in men and women of all ages with and without cardiovascular disease. Data gathered from clinical trials suggest that HR reduction is an important mechanism of benefit of HR-lowering drugs. A high HR has direct detrimental effects not only on myocardial ischemia but also on the progression of atherosclerosis, ventricular arrhythmias, and on left ventricular function. The risk increases with HR >60 b.p.m. Ivabradine, a drug that slows HR though an effect on the If channels, has been approved for the control of myocardial ischemia in patients with coronary artery disease intolerant to beta-blockers. More recently, the indication of ivabradine has been extended for use in association with beta-blockers in patients with coronary artery disease. The effects of ivabradine on myocardial ischemia are greater than those predicted by pure HR reduction with beta-blockers, suggesting additional mechanisms of action.     

Sex-specific predictors of utilization of cardiologic rehabilitation from the epidemiologic viewpoint

Among men and women cardiovascular diseases are among the three main causes for early retirement and participation in rehabilitation programmes. Rehabilitation research has only recently taken notice of the potential effect of gender on the need and outcome of cardiac rehabilitation care. Findings from epidemiological studies suggest that sex differences exist at every stage of heart disease and therefore may also be important for the quality and quantity of gender specific rehabilitation needs. Based on results from epidemiological studies this article first describes some essential biomedical differences between men and women regarding coronary heart disease which should be taken into account when type and amount of rehabilitation programmes are discussed. Afterwards, some recent findings are presented which focus on gender specific aspects of the use and acceptance of rehabilitation procedures.     

性别因素对心力衰竭住院患者病因和预后的影响

目的调查不同性别对心力衰竭住院患者病因和预后的影响。方法 1993年1月至2007年12月初次住院有效诊断充血性心力衰竭患者6949例(男4344例,女2605例),按照性别不同分成2组,比较各组间的病因及30 d在院病死率。结果心力衰竭住院患者中,男性病因以冠心病(49.6%)、高血压(39.3%)和心肌病(8.0%)为主。而女性以瓣膜性心脏病(37.5%),肺心病(10.6%)和甲亢(1.0%)为主。在18～29岁人群组,女性的死亡率几乎为男性的3倍(4.8%vs 1.7%);在≥80岁以上人群组,女性死亡率显著高于男性(16.1%vs 11.4%)。随着年龄增长,男性和女性死亡率均增加。结论性别不同,心力衰竭住院患者的病因和在院死亡率不同。     

Survival in patients with hypertension treated in primary care. A population-based follow-up study in the Skaraborg Hypertension and Diabetes Project

OBJECTIVE: To explore risk factors for all-cause mortality in patients with hypertension. DESIGN: Community-based cohort study. SETTING: Hypertension outpatient clinic in primary health care. SUBJECTS: Hypertensive men and women who consecutively underwent an annual follow-up during 1992--1993 (n =894). METHODS: Vital status was ascertained up to December 1999 by record linkage with national registers. Gender-specific predictors for mortality from baseline examination were analysed by Cox regression. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: In both sexes all-cause mortality was predicted by fasting blood glucose (RR by 1 mmol L(-1): 1.2, CI: 1.1-1.3 in men; 1.2, 1.1-1.4 in women), and known type 2 diabetes (RR: 1.9, CI: 1.3-2.9 in men; 2.5, 1.7-3.9 in women). In men, furthermore, mortality was predicted by previous cardiovascular disease, left ventricular hypertrophy and microalbuminuria, whilst in women mortality was predicted by high blood pressure and dyslipidemia. In patients without known diabetes male gender was a strong predictor of mortality (RR: 2.0, CI: 1.4-2.9), whereas in patients with hypertension and type 2 diabetes combined, male gender was not associated with increased mortality (RR: 1.4, CI: 0.9-2.2). CONCLUSION: Type 2 diabetes in hypertensive patients treated in primary care predicts mortality and dilutes gender difference in survival. For hypertensive patients general practitioners should be observant regarding disturbed glucose metabolism and regarding the associated major risk increase in women.     

Influence of age and gender on autonomic regulation of heart

Heart rate variability (HRV) is a non-invasive method to measure cardiac autonomic function. Impairments in HRV have been proposed as independent risk factor for increased cardiac mortality and morbidity. Cardio protective phenomenon in females has been hypothesized to be due to differential autonomic tone. Age related loss of vagal control has been reported as predisposing factor for the development of cardiovascular disease. In this study we assessed effect of age and gender on autonomic regulation of heart in healthy volunteers. HRV data of 189 subjects (114 males and 75 females) were analyzed in time and frequency domains using customized program. Artifact free 5 min electrocardiogram segment was used for analysis. It was ensured that none of the subject had medical illness such as diabetes, hypertension, thyroid disorders, cardiac disorders, diseases potentially related with autonomic neuropathy and major psychiatric illness by careful history and clinical examination. HRV recordings were done under standard laboratory condition. On correlation analysis SDNN, RMSSD, total power negatively correlated with age suggesting reduced autonomic regulation of heart with increase in age (SDNN: r = ?0.444, p < 0.01; RMSSD: r = ?0.552, p < 0.01; total power: r = ?0.474, p < 0.01); similarly High frequency power (HF.nu) negatively correlated with age (r = ?0.167, p = 0.02), denoting loss of vagal tone with aging. LF/HF ratio correlated positively with age (r = 0.19, p < 0.01) suggesting a relative increase of sympathetic activity with increase in age. On multiple regression analysis to control for effect of age and heart rate while comparing males and females, LF.nu showed significant reduction suggesting lower sympathetic tone in females (β = ?6.64; p < 0.01) and HF.nu showed increase at trend level (β = 4.47; p = 0.053). In conclusion, there is overall reduction in autonomic control of heart with increase in the age. Sympathetic tone predominates and vagal tone diminishes with aging process. Females showed greater vagal tone than male. This differential autonomic tone indicate age, gender related predisposition to cardiovascular disease.     

Female gender is associated with a better outcome after cardiac resynchronization therapy

Background: Some studies have suggested that women respond differently to cardiac resynchronization therapy (CRT). We sought to determine whether female gender influences long‐term clinical outcome, symptomatic response as well as echocardiographic response after CRT. Methods and Results: A total of 550 patients (age 70.4 ± 10.7 yrs [mean ± standard deviation]) were followed up for a maximum of 9.1 years (median: 36.2 months) after CRT‐pacing (CRT‐P) or CRT‐defibrillation (CRT‐D) device implantation. Outcome measure included mortality as well as unplanned hospitalizations for heart failure or major adverse cardiovascular events (MACE). Female gender predicted survival from cardiovascular death (hazard ratio [HR]: 0.52, P = 0.0051), death from any cause (HR: 0.52, P = 0.0022), the composite endpoints of cardiovascular death /heart failure hospitalizations (HR: 0.56, P = 0.0036) and death from any cause/hospitalizations for MACE (HR: 0.67, P = 0.0214). Female gender predicted death from pump failure (HR: 0.55, P = 0.0330) but not sudden cardiac death. Amongst the 322 patients with follow‐up echocardiography, left ventricular (LV) reverse remodelling (≥15% reduction in LV end‐systolic volume) was more pronounced in women (62% vs 44%, P = 0.0051). In multivariable Cox proportional hazards analyses, the association between female gender and cardiovascular survival was independent of age, LV ejection fraction, atrial rhythm, QRS duration, CRT device type, New York Heart Association (NYHA) class, and LV reverse remodelling (adjusted HR: 0.48, P = 0.0086). At one year, the symptomatic response rate (improvement by ≥1 NYHA classes or ≥25% increase in walking distance) was 78% for both women and men. Conclusions: Female gender is independently associated with a lower mortality and morbidity after CRT. (PACE 2011; 82–88)     

Endothelin, sex and hypertension

The ETs (endothelins) comprise a family of three 21-amino-acid peptides (ET-1, ET-2 and ET-3) and 31-amino-acid ETs (ET-1(1-31), ET-2(1-31) and ET-3(1-31)). ET-1 is synthesized from a biologically inactive precursor, big ET-1, by ECEs (ET-converting enzymes). The actions of ET-1 are mediated through activation of the G-protein-coupled ET(A) and ET(B) receptors, which are found in a variety of cells in the cardiovascular and renal systems. ET-1 has potent vasoconstrictor, mitogenic, pro-inflammatory and antinatriuretic properties, which have been implicated in the pathophysiology of a number of cardiovascular diseases. Overexpression of ET-1 has been consistently described in salt-sensitive models of hypertension and in models of renal failure, and has been associated with disease progression. Sex differences are observed in many aspects of mammalian cardiovascular function and pathology. Hypertension, as well as other cardiovascular diseases, is more common in men than in women of similar age. In experimental models of hypertension, males develop an earlier and more severe form of hypertension than do females. Although the reasons for these differences are not well established, the effects of gonadal hormones on arterial, neural and renal mechanisms that control blood pressure are considered contributing factors. Sex differences in the ET-1 pathway, with males displaying higher ET-1 levels, greater ET-1-mediated vasoconstrictor and enhanced pressor responses in comparison with females, are addressed in the present review. Sex-associated differences in the number and function of ET(B) receptors appear to be particularly important in the specific characteristics of hypertension between females and males. Although the gonadal hormones modulate some of the differences in the ET pathway in the cardiovascular system, a better understanding of the exact mechanisms involved in sex-related differences in this peptidergic system is needed. With further insights into these differences, we may learn that men and women could require different antihypertensive regimens.     

Oestrogens and the heart.

The incidence of cardiovascular disease is lower in women before the menopause compared with men, while menopausal women have an incidence of coronary disease similar to that of men of the same age. This is mainly dependent upon oestrogen deficiency. Large-scale epidemiological studies have demonstrated that oestrogen replacement therapy leads to approximately 50 per cent reduction of cardiovascular disease in women taking hormones, compared with untreated women. Multiple mechanisms have been proposed to explain the cardiovascular risk reduction observed in women on oestrogen therapy. Oestrogens positively affect plasma lipids and exert a beneficial effect upon carbohydrate metabolism and the haemocoagulation profile. Oestrogens may also have anti-atherogenic properties. Recent in vitro studies have demonstrated that oestrogens may positively influence all the steps involved in the formation of the atherosclerotic plaque (accumulation of cholesterol in the arterial wall, arterial smooth muscle cell proliferation, platelet aggregation, collagen and elastin production). Angiographic studies conducted in humans have demonstrated that women on oestrogens have significantly less coronary disease and less severe occlusion scores compared with women not taking hormone replacement therapy. Animal and human studies have shown that oestrogens act as vasodilating substances. Endothelium-dependent mechanisms have been identified and imply that oestrogens act through the endothelial release, mainly, of nitric oxide, a potent vasodilating substance which has been identified with EDRF (endothelium derived relaxing factor). More recently, oestrogens have been shown to affect also the vascular tone in the absence of the endothelium. Therefore, endothelium-independent mechanisms could be involved in the pathogenesis of the oestrogens' vascular effects. There is evidence that oestrogens have calcium antagonistic properties; this mechanism may be responsible for the reduction of peripheral vascular resistance observed in women on hormone replacement therapy and may slow the progression of coronary artery disease. The menopausal age is characterized by an imbalance of the neurohormonal system. Sudden increases of plasma catecholamines are evident when women have hot flushes, a typical clinical sign of the menopausal period. The abnormal release of catecholamines may reduce coronary flow reserve and increase peripheral vascular resistance and, therefore, may be dangerous for the heart. It has been shown, by means of the study of heart rate variability, that oestrogens are effective in modulating the neurohormonal system. The reduction of sympathetic tone has beneficial effects on coronary flow reserve and may be important in explaining the cardioprotective effect of oestrogens. Peripheral and coronary vasodilation observed in women on hormone replacement therapy might be also due to the inhibition of the release of vasoconstrictor factors such as endothelin-1 by oestrogens. Therefore, oestrogens protect the heart against coronary artery disease and they are now regarded as being as important as aspirin and antihypertensive drugs were in the past. Hormone replacement therapy should be considered in every menopausal woman to possibly prevent the occurrence of cardiovascular disease or, if already present, to slow its progression.     

Sleep Apnea:

In the general adult population, prevalence of sleep apnea syndrome reaches 4% in men and 2% in women. Continuous positive airway pressure is the most efficient treatment. At the present time, although severe atrial bradycardias could occur during sleep apnea episodes, cardiac pacing has not been demonstrated as an efficient treatment for those bradycardias. Treating sleep apnea generally reduces the number of bradyarrhythmias. However, recent studies reported a beneficial effect of atrial pacing on the sleep apnea burden. The mechanisms rely on two phenomena: first to counteract nocturnal hypervagotonia, and second to treat heart failure. By increasing the heart rate, cardiac output improves, which mitigates pulmonary subedema. Consequently, stimulation of the pulmonary afferent vagal fibers is diminished, which reduces central sleep apnea incidence. During nocturnal hypervagotonia, snoring and obstructive apnea episodes are increased, mainly due to an excessive muscular relaxation of the upper airway area inducing cyclical substantial decreases in the airway caliper. In patients with a low heart rate, atrial pacing can counteract hypervagotonia by enhancing the sympathetic tone and modifying the degree of vigilance. Accordingly, in the near future, sleep apnea treatment might potentially rely on atrial pacing in bradycardic patients with hypervagotonia (with or without heart failure). The role of the physician would then be not only to diagnose sleep apnea, but also to identify potential responders to cardiac pacing.     

Essential hypertension: neural considerations

Current evidence suggests that the sympathetic nervous system plays a predominant role in some fraction of essential hypertension. Patients in whom such mechanisms are likely to be operative are young people with mild or labile hypertension. These mechanisms are expressed clinically through orthostatic hypertension, rapid heart rate, modestly elevated cardiac output, and normal or slightly elevated peripheral vascular resistance. The vascular resistance is inappropriately high for the level of cardiac output, and this is reflected in a mildly elevated blood pressure. This evidence carries therapeutic implications and suggests that sympatholytic drugs should be the first line of therapy. An additional pressor mechanism may arise from increased sympathetic activity along renal efferent nerves that impairs sodium excretion and another possible mechanism is stimulation of brain centers through impulses from the kidneys carried in renal afferent nerves.     

Gender differences in acute coronary events.

The most frequent cause of death among women in the United States is coronary heart disease, which claims 200,000 lives a year. The prognosis with either medical or surgical therapy is worse in females than in males. The following significant gender differences have been observed and reported: (1) the rate of early death following acute myocardial infarction is greater in women, (2) the difference between sexes remains whether or not thrombolytic therapy is used, and (3) the hospital mortality rate following coronary angioplasty, atherectomy, or bypass surgery is greater in females. The reasons for these gender differences are not clearly understood. Nevertheless, awareness of the higher morbidity and mortality in women dictates the need for early detection and more aggressive therapy of the risk factors. However, diabetes mellitus and essential hypertension are 2 well-established major risk factors for coronary disease and stroke that are more prevalent in the female gender. These 2 risk factors are cumulative and require more intensive and aggressive therapy to prevent acute vascular events, and therefore early detection is mandatory.     

Morbidity and mortality rates in women with heart disease: lessons in gender differences from Korea

Korean health statistics and available research were reviewed, focusing on the gender differences in morbidity and mortality rates of heart disease, and factors affecting health outcomes of heart disease internationally with Korea. The growth rate and aging of population, and the morbidity and mortality rate from heart disease among Koreans were compared to the data provided by the World Health Organization (WHO) and the United Nations (UN). Both morbidity and mortality rates from heart disease were higher among women than among men in Korea. However, most of the knowledge about heart disease was based on research conducted on men, and not much is known about women with heart disease. The lack of information about women with heart disease may contribute to delay in diagnosis and treatment, longer stays in the hospital, increased medical costs and a higher mortality rate among women than among men in Korea.