Scandinavian cardiovascular journal. Supplement最新文献

Objective: To review studies of effects of antihypertensive agents on alterations in structure and function of small (resistance-size) arteries in hypertensive patients and in experimental hypertensive models, since these vessels may contribute to blood pressure elevation or to the complications of hypertension.

Main outcome measures: The structure and endothelium-dependent relaxation of small arteries obtained in hypertensive humans from gluteal subcutaneous biopsies, and from different vascular beds in hypertensive rats, without and after antihypertensive treatment, and studied on a wire-myograph or as pressurized arteries, are described as reported in different studies.

Results: Treatment of spontaneously hypertensive rats (SHR) with angiotensin converting enzyme (ACE) inhibitors, calcium channel antagonists, angiotensin receptor antagonists and novel beta blockers such as carvedilol, has been shown to result in regression of the altered structure of small arteries in different vascular beds, in addition to improved endothelium-dependent relaxation. Several studies in hypertensive patients have now shown that treatment with some ACE inhibitors (cilazapril and perindopril) or extended release calcium channel antagonists (nifedipine GITS) induces similar effects in small arteries obtained from gluteal subcutaneous biopsies: both structure and endothelium-dependent relaxation improve under treatment. In contrast, hypertensive patients with equally well-controlled blood pressure but treated with the beta blocker atenolol did not in any of three studies exhibit any improvement in the structure of small arteries or in endothelial function.

Conclusion: Although treatment for at least one year with some ACE inhibitors and extended release calcium channel antagonists corrects the structure and endothelium-dependent relaxation of gluteal subcutaneous small arteries, it still remains to be determined whether this apparently beneficial effect beyond blood pressure lowering of these and other agents with vascular protective properties will result in reduced morbidity and mortality in hypertensive patients.

The reduction of coronary mortality is not as large as one would expect from the observed blood pressure lowering in trials of antihypertensive medications. This is not surprising; hypertension is a complex disease where the high blood pressure is only one of numerous coronary risk factors. Sympathetic overactivity in hypertension, independent of the blood pressure, may be conducive to premature atherosclerosis by inducing insulin resistance and dyslipidemia. Through its trophic effect on blood vessels, sympathetic overactivity potentiates vasoconstriction. This, in turn, accelerates hypertension and the metabolic syndrome. The hypertrophy of small coronary arterioles decreases the coronary reserve and enhances coronary spasms. Tachycardia, which is due to increased sympathetic tone and a decreased parasympathetic tone, favors arrhythmias and sudden death in congestive heart failure and hypertension. Increased hematocrit is frequently found in male patients with hypertension, and high hematocrit is a predictor of coronary heart disease/thrombosis. The increase of hematocrit is in part due to an alpha adrenergic postcapillary venoconstriction. Enhanced sympathetic drive, insulin resistance and dyslipidemia have been demonstrated also in congestive heart failure, but the clinical importance of these findings is not fully understood.

In several experimental animal models of hypertension, sympathetic factors have been shown to be involved in the development and/or maintenance of high blood pressure. Although the information available on this issue in man is more scarce, recent evidence clearly indicates the participation of adrenergic mechanisms in the early and late phases of the hypertensive process. In addition, several cardiovascular risk factors frequently associated with hypertension, such as obesity, insulin-resistance, cigarette smoking, and the atherogenic process, are also characterized by alterations in sympathetic cardiovascular drive. This contributes to a further activation of the sympathetic nervous system thus favoring the development of the end organ damage (e.g. cardiac and vascular hypertrophy) associated with the hypertensive state.

A large number of prospective intervention trials have clearly demonstrated that drug treatment of hypertension lower cardiovascular morbidity and mortality. In the elderly, where treatment results in higher absolute decreases in morbidity and mortality, drug treatment is clearly cost-effective or even cost-saving in some groups of patients. Although the concept of treating hypertension is generally well accepted, a significant portion of patients remain insufficiently treated. In spite of major advances in the management of hypertension during the last decades, there is an excess morbidity and mortality in the hypertensive population. Thus, treatment is still imperfect, and a number of measures need to be taken in order to bring down cardiovascular risk in hypertensive patients to that of the normotensive population.

Arterial hypertension used to be the most common cause of congestive left ventricular failure. With the availability and common use of antihypertensive treatment the incidence and prevalence of hypertension-induced left ventricular failure has gradually declined. Today congestive heart failure due to underlying coronary heart disease is by far more common than the hypertension-induced variety. The effect of treatment of left ventricular failure in recent years, in particular with angiotensin converting enzyme inhibitors and carvedilol, has been impressive.

Heart failure is a common disease characterised by poor prognosis and frequent hospitalisations, constituting a major economic burden to society. Mortality and morbidity can be reduced by optimal treatment, requiring objective evaluation of cardiac function and anatomy. The development of symptomatic HF can be prevented by initiating adequate treatment in early stages when LVD is still asymptomatic. Asymptomatic patients can be identified only by screening for LVD among patients at risk of developing HF, such as those with IHD, HT, and diabetes. However, there is a severe lack of resources to assess cardiac function and anatomy in all patients at risk. Consequently, many patients with latent HF will remain undetected, and in patients with symptomatic HF treatment will not be optimal. Simplified echocardiography, a 5-minute echocardiogram based on visual estimation of cardiac function and anatomy, is an inexpensive and accurate method for diagnosis and screening for latent and symptomatic HF. The long axis shortening of the LV is related to LV function and can be measured by AVPD. Determination of left AVPD is a reliable, reproducible, readily mastered, quickly performed and, therefore, inexpensive method that can be used in almost all patients for evaluation of LV function, as well as for prognostication in HF. Left AVPD reflects both systolic and diastolic LV function. Simplified echocardiography is useful for screening of asymptomatic patients at risk of developing HF, and for routine diagnostic purposes in patients with symptoms suggestive of HF. In patients with LVSD, simplified echocardiography may be combined with a determination of left AVPD for prognostication and for optimal detection of changes in LV function over time.

The manifestation of congestive heart failure occurs secondary to a great variety of cardiac or systemic disorders that share a temporal or permanent loss of cardiac function. In order to enhance our knowledge about the genetics of heart failure it is mandatory to analyse the aetiologic factors of these underlying disorders separately. Monogenic forms of congestive heart failure have initially been described by observant physicians in consecutive generations of affected families. Molecular genetic analyses of these families subsequently allowed us to localise and identify some of the genes that cause hypertrophic, dilative, or restrictive cardiomyopathies, congenital heart disease, as well as a number of inborn errors of metabolism. However, the great majority of patients develops heart failure as a final consequence of multifactorial conditions such as hypertension, cardiac hypertrophy, or coronary artery disease. Each of these conditions may be the product of a complex equation that includes environmental and genetic factors. Indeed, some of these factors may be harmful, others protective and for most it takes decades before a phenotype will be clinically detectable. Given this complex scenario it was not unexpected that early studies on candidate genes came up with partially controversial information. This review aims to summarize and to comment on the principal findings of this work.