Clinical Impact of Left Ventricular Hypertrophy and Implications for Regression

Left ventricular hypertrophy (LVH) is an independent risk factor and predictor of cardiovascular (CV) events and all-cause mortality. Patients with LVH are at increased risk for stroke, congestive heart failure, coronary heart disease, and sudden cardiac death. Left ventricular hypertrophy represents both a manifestation of the effects of hypertension and other CV risk factors over time as well as an intrinsic condition causing pathologic changes in the CV structure and function. We review the risk factors for LVH and its consequences, concentric remodeling, and its prognostic significance, clinical benefits and supporting evidence for LVH regression, and its implications for management. We conclude our review summarizing the various pharmacological and nonpharmacological therapeutic options approved for the treatment of hypertension and LVH regression and the supporting clinical trial data for these therapeutic strategies.     

Hypertrophy of left ventricular myocardium as modifiable risk factor: novel possibilities of correction

Hypertrophy of left ventricular myocardium observed in 15-20% of patients with arterial hypertension is an independent factor which elevates considerably risk of complications of hypertension (ischemic heart disease, chronic heart failure, ventricular arrhythmias). Regression of left ventricular hypertrophy (LVH) at the background of hypotensive therapy is associated with additional lowering of cardiovascular risk. This should be taken into consideration in selection of a hypotensive preparation. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are believed to have most pronounced ability to cause reverse development of LVH. It has been shown in recently finished PIXEL trial that administration of fixed combination of ACEI perindopril and diuretic indapamide reduced LVH more effectively than monotherapy with high doses of ACEI enalapril and provided better blood pressure control. Therefore in a patient with hypertension and LVH it is expedient to consider combined therapy with ACEI and diuretic including use of their fixed combinations as treatment of choice.     

Antihypertensive drugs and the heart

Left ventricular hypertrophy (LVH) and diastolic dysfunction (CHF-D) are early signs of cardiac end-organ damage (hypertensive heart disease) in patients with arterial hypertension. The presence of LVH or CHF-D confers increased risk of cardiovascular morbidity and mortality in patients with hypertension. Regression of left ventricular mass with antihypertensive therapy is associated with reduction in cardiovascular events. Antihypertensive therapy should be geared to both lower blood pressure and specifically reverse the pathophysiologic processes that may be independent of actual blood pressure. This review summarizes current and emerging approaches to the treatment of individuals with hypertensive heart disease.     

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高血压左心室肥厚(LVH)的发生除与血压相关外还与生物力学、神经体液及遗传因素相关。循证医学证据表明,LVH是冠心病、心力衰竭、心脏猝死及脑卒中等心血管事件的独立危险因素。长期有效地降压治疗可以在很大程度上逆转LVH,并减少与之相关的心血管事件。     

ACE inhibitors and regression of left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is a common condition and a powerful independent risk factor for coronary heart disease, congestive heart failure, and other cardiac morbidity. It is associated with the male sex and advancing age. Its most common cause is hypertension, and many antihypertensive agents induce regression of LVH. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reverse LVH by a mechanism as yet unknown. Reduction in afterload and other hemodynamic abnormalities by reduction of blood pressure is clearly a factor, but ACE inhibitors also block adrenergic action and other sympathetic nervous system influences, and the reduction in angiotensin II produces many effects. By inhibiting this potent vasoconstrictor and suppressing its degradation of the powerful vasodilator bradykinin, and by promoting sodium and water excretion, ACE inhibitors contribute to the restoration of normal ventricular function. Angiotensin II promotes protein synthesis in myocardial myocytes, and blocking this action may arrest the hypertrophic process. To determine the effect of angiotensin II on LVH and normalization of LV function, a study is now underway evaluating the effects of lisinopril, a new lysine analog of enalapril, and a diuretic agent in the treatment of hypertension LVH.     

Impact of Echocardiographic Left Ventricular Geometry on Clinical Prognosis

Abnormal left ventricular (LV) geometry, including LV hypertrophy (LVH), is associated with increased risk of major cardiovascular (CV) events and all-cause mortality and may be an independent predictor of morbid CV events. Patients with LVH have increased risk of congestive heart failure, coronary heart disease, sudden cardiac death and stroke. We review the risk factors for LVH and its consequences, as well as the risk imposed by concentric remodeling (CR). We also examine evidence supporting the benefits of LVH regression, as well as evidence regarding the risk of CR progressing to LVH, as opposed to normalization of CR. We also briefly review the association of abnormal LV geometry with left atrial enlargement and the combined effects of these structural cardiac abnormalities.     

Abnormalities of kidney function as a cause and a consequence of cardiovascular disease

Hypertension, left ventricular hypertrophy (LVH), hypercreatininemia, and microalbuminuria (MA) are independent risk factors for cardiovascular disease (CVD). Hypertension increases the risk of CVD by two- to three-fold and LVH (especially concentric) is a risk factor for coronary heart disease, heart failure, stroke, and peripheral arterial disease. In people with hypertension, a serum creatinine level of 1.7 mg/dL or more may be an even stronger CVD risk factor than diabetes, smoking, LVH, or systolic blood pressure. Similarly, MA is a strong and independent predictor of CVD morbidity and mortality in people with and without diabetes and/or hypertension. Impaired renal sodium handling and sodium retention are physiological hallmarks of the very early stages of heart failure. Heart failure is a physiologically delicate condition that can decompensate with excess dietary salt intake or over diuresis, or compensate with cautious therapy designed to block the sodium retention and simultaneously interrupt excessively activated neurohumoral mechanisms.     

From left ventricular hypertrophy to congestive heart failure: management of hypertensive heart disease

Other than age, left ventricular hypertrophy (LVH) is the most potent predictor of adverse cardiovascular outcomes in the hypertensive population, and is an independent risk factor for coronary heart disease, sudden death, heart failure and stroke. Although directly related to systolic blood pressure, other factors including age, sex, race, body mass index and stimulation of the renin-angiotensin-aldosterone and sympathetic nervous systems play an important role in the pathogenesis of LVH. LVH involves changes in myocardial tissue architecture consisting of perivascular and myocardial fibrosis and medial thickening of intramyocardial coronary arteries, in addition to myocyte hypertrophy. The physiologic alterations which occur as a result of these anatomical changes include disturbances of myocardial blood flow, the development of an arrhythmogenic myocardial substrate and diastolic dysfunction. The latter is directly related to the degree of myocardial fibrosis and is the hemodynamic hallmark of hypertensive heart disease. When diastolic dysfunction is present, left ventricular end-diastolic pressure increases out-of-proportion to volume and may be elevated at rest or with exertion leading to clinical heart failure. At least one third of heart failure patients in the United States can be considered to have heart failure related to diastolic dysfunction. Compared to heart failure patients with systolic dysfunction, diastolic heart failure patients are more likely to be older, female, and to be hypertensive at the time of presentation. Although it has been assumed that LVH may lead to systolic dysfunction, evidence is lacking that LVH resulting from hypertension is a major risk factor for systolic heart failure independent of coronary artery disease. Treatment of hypertension greatly attenuates the development of LVH and significantly decreases the incidence of heart failure. In patients with established LVH, regression is both possible and desirable and results in a significant reduction in adverse clinical endpoints.     

Conventional and new electrocardiographic criteria for hypertension‐mediated cardiac organ damage: A narrative review

Hypertension‐mediated organ damage (HMOD) is frequently observed in hypertensive patients at different cardiovascular (CV) risk profile. This may have both diagnostic and therapeutic implications for the choice of the most appropriate therapies. Among different markers of HMOD, the most frequent functional and structural adaptations can be observed at cardiac level, including left ventricular hypertrophy (LVH), diastolic dysfunction, aortic root dilatation, and left atrial enlargement. In particular, LVH was shown to be a strong and independent risk factor for major CV events, namely myocardial infarction, stroke, congestive heart failure, CV death. Thus, early identification of LVH is a key element for preventing CV events in hypertension. Although echocardiographic assessment of LVH represents the gold standard technique, this is not cost‐effective and cannot be adopted in routine clinical practice of hypertension. On the other hand, electrocardiographic (ECG) assessment of HMOD relative to the heart is a simple, reproducible, widely available and cost‐effective method to assess the presence of LVH, and could be preferred in large scale screening tests. Several new indicators have been proposed and tested in observational studies and clinical trials of hypertension, in order to improve the relatively low sensitivity of the conventional ECG criteria for LVH, despite high specificity. This article reviews the differences in the use of the main conventional and the new 12 lead ECG criteria of LVH for early assessment of asymptomatic, subclinical cardiac HMOD in a setting of clinical practice of hypertension.     

Left ventricular hypertrophy: a potent cardiovascular risk factor and its relationship to office and ambulatory blood pressure

Left ventricular hypertrophy (LVH) is an important cardiovascular risk factor. The presence of LVH carries risk independent of hypertension. LVH can be detected non-invasively using electrocardiography or echocardiography. Clinical studies have consistently shown that ambulatory blood pressure is a stronger correlate of left ventricular mass than office blood pressure. Furthermore, treatment-induced decreases in left ventricular mass index are also more tightly related to reductions in ambulatory blood pressure than reductions in office blood pressure. The primary intervention for subjects with hypertension and LVH is optimal blood pressure control. Several small studies now suggest that therapeutic changes resulting in regression of left ventricular mass also confer a reduction in cardiovascular risk. Therefore, LVH is a serious negative risk factor that is more closely related ambulatory rather than office blood pressure. Fortunately, current evidence suggests that optimal antihypertensive therapy resulting in regression of hypertrophy will reduce at least short-term cardiovascular events. Physicians need to be more aware of LVH as a cardiovascular risk factor.     

Optimal antihypertensive therapy for prevention and treatment of left ventricular hypertrophy

Left ventricular hypertrophy (LVH) is considered an adaptation to a pressure load on the left ventricle and is common in hypertensive patients. The condition is a profound risk factor for cardiovascular events, greater than and independent of blood pressure. It is now recognized in hypertension management guidelines as an indication for more stringent blood pressure control. All of the first-line antihypertensive agents have been shown to variably regress LVH, but no definitive evidence yet shows that one agent is superior to others in decreasing risk independent of blood pressure control. Although some evidence suggests that reduction of LVH is associated with improved prognosis independent of blood pressure control, relative efficacy of drug classes in this regard has yet to be demonstrated. At present, recommendations for optimal therapy in hypertensive patients with LVH must rest on the presence of underlying cardiac and noncardiac conditions, with the understanding that the major classes of antihypertensive agents will probably decrease LVH.     

Hypertension,left ventricular hypertrophy and chronic kidney disease

Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease. LVH in CKD patients has generally a negative prognostic value, because it represents an independent risk factor for the development of arrhythmias, sudden death, heart failure and ischemic heart disease. LVH in CKD patients is secondary to both pressure and volume overload. Pressure overload is secondary to preexisting hypertension, but also to a loss of elasticity of the vessels and to vascular calcifications, leading to augmented pulse pressure. Anemia and the retention of sodium and water secondary to decreased renal function are responsible for volume overload, determining a hyperdynamic state. In particular, the correction of anemia with erythropoietin in CKD patients is advantageous, since it determines LVH reduction. Other risk factors for LVH in CKD patients are documented: some are specific to CKD, as mineral metabolism disorders (hypocalcemia, hyperphosphatemia, low serum vitamin D levels and secondary hyperparathyroidism), others are non-traditional, such as increased asymmetric dimethylarginine, oxidative stress, hyperhomocysteinemia and endothelial dysfunction that, in turn, accelerates the process of atherogenesis, triggers the inflammation and pro-thrombotic state of the glomerular and the vascular endothelium and aggravates the process of both CKD and LVH.     

中老年心脑血管事件患者危险因素的探讨

目的:评估中、老年人心脑血管危险因素与心脑血管事件发生的关系。方法:采取病例配对的方法,对98例首次发生心脑血管事件患者进行心血管危险因素分析,对照组随机选择同期因呼吸、消化疾病住院的中老年患者。以心脑血管事件为因变量,以各种危险因素为自变量,进行logistic逐步回归分析,并对事件组患者进行危险因素的回顾性探讨。结果:事件组收缩压(SBP)、舒张压(DBP)、脉压(PP)、静息心率(RHR)、血糖(GLU)、总胆固醇(TC)、甘油三酯(TG)均高于对照组,STT异常、左室肥厚(LVH)发生率较高。logistic回归分析表明:LVH、TG、TC、PP、RHR、STT异常与心脑血管事件呈正相关,有显著统计学意义。结论:高血压、高血脂、静息心率增快、STT异常、左室肥厚等心血管危险因素与心脑血管事件的发生密切相关,随着年龄增高,单纯收缩期高血压、脉压升高是心脑血管事件的最常见危险因素。     

Hypertensive heart disease.

Left ventricular hypertrophy (LVH) and diastolic dysfunction (CHF-D) are the early manifestations of cardiovascular target organ damage in patients with arterial hypertension and signify hypertensive heart disease. Identification of hypertensive heart disease is critical, as these individuals are more prone to congestive heart failure, arrhythmias, myocardial infarction and sudden cardiac death. Regression of left ventricular (LV) mass with antihypertensive therapy decreases the risk of future cardiovascular events. The goal of antihypertensive therapy is to both lower blood pressure (BP) and interrupt BP-independent pathophysiologic processes that promote LVH and CHF-D. The purpose of this review is to summarize current and emerging approaches to the pathophysiology and treatment of hypertensive heart disease.     

Regression of left ventricular hypertrophy and cardiovascular risk changes in hypertensive patients.

Hypertensive left ventricular hypertrophy (LVH) may be detected in about one third of people with hypertension. When an individual with elevated blood pressure develops LVH, the risk of adverse cardiovascular events in the ensuing years almost doubles even in the absence of symptoms. Because of this high added risk, hypertension and other modifiable risk factors should be managed aggressively with lifestyle measures and drugs. LVH can be considered a biological assay which reflects and integrates the long-term exposure not only to pressure overload, but also to several hemodynamic and non-hemodynamic factors which may promote progression and instabilization of atherosclerotic lesions and, ultimately, lead to adverse clinical events. LVH can partially or totally regress following antihypertensive treatment and lifestyle changes including losing excessive weight and decreasing salt intake. Angiotensin II antagonists and ACE-inhibitors seem to be the most effective drugs for reversing LVH. Evidence is accumulating that regression of LVH is associated with a significant reduction in the subsequent risk of cardiovascular disease. According to a recent meta-analysis, effective reversal of LVH is associated with a 59% lesser risk of subsequent adverse events as compared with the persistence or new development of LVH.     

Left ventricular hypertrophy as a predictor of coronary heart disease mortality and the effect of hypertension

BACKGROUND: Although associations between hypertension, left ventricular hypertrophy (LVH), and coronary heart disease (CHD) have been described, it is less clear whether LVH is associated with increased rates of CHD in the absence of hypertension. METHODS: We examined this association with Cox regression analyses of data from 7924 adults 25 to 74 years of age from the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study (1976 to 1992). Covariates included age, race, sex, history of cardiovascular diseases and diabetes, cholesterol, body mass index, blood pressure, and smoking. RESULTS: During 16.8 follow-up years, there were 462 (26%) deaths from CHD (ICD-9 410-414) and 667 (38%) deaths from diseases of the heart (ICD-9 390-398, 402, 404, 410-414, 415-417, 420-429). LVH prevalence was 13.3 per 1000 population. Hypertension prevalence was 29.1%. LVH prevalence was higher among hypertensive adults than among normotensive adults (29.9 vs 6.4 per 1000, P <.001). Persons with LVH were twice as likely to die of CHD (relative risk, 2.0; 95% confidence interval, 1.2, 3.5) and diseases of the heart (relative risk, 1.9; 95% confidence interval, 1.1, 3.0) after adjustment for hypertension and covariates. In age-adjusted predicted survival, probability plots for CHD, and diseases of the heart, normotensives with LVH had survival similar to hypertensive adults with LVH and lower survival than normotensive and hypertensive adults with no LVH. CONCLUSIONS: Our results confirm previous findings that the presence of LVH is a strong predictor of future cardiovascular death. Although LVH appears to be rare among normotensives, clinicians should be aware that such individuals may have an increased risk for death similar to that of hypertensive adults with LVH.     

Are all antihypertensive drug classes equal in reducing left ventricular hypertrophy?

Left ventricular hypertrophy (LVH) is a major cardiovascular risk factor for morbidity and mortality. It is caused by arterial hypertension, although various hemodynamic and nonhemodynamic factors contribute to its development. Especially, the renin-angiotensin-aldosterone system is involved in the pathophysiology of LVH. The Treatment of Mild Hypertension study demonstrated that in mild essential hypertension, nonpharmacologic treatment is an effective tool for treating LVH. There are at least three major meta-analyses with several thousand patients examining the ability of antihypertensive drugs on the reversal of LVH. The results of these meta-analyses are very consistent. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers achieve significantly better results than β-blockers. The most recently published Losartan Intervention For Endpoint reduction in hypertension study confirmed the superiority of angiotensin receptor blockers against β-blockers in a large-scale prospective trial. It also proves for the first time that regression of LVH is associated with better cardiovascular outcome.     

Comprehensive assessment of hypertensive heart disease: cardiac magnetic resonance in focus

Arterial hypertension represents the most frequent cardiovascular risk factor that is associated with cardiac remodeling. Hypertensive heart disease was defined by the presence of left ventricular hypertrophy (LVH) and diastolic dysfunction, and it has been diagnosed by echocardiography in everyday clinical practice. Interstitial myocardial fibrosis is the underlying cause of hypertension-induced cardiac remodeling, and it could not be visualized with different echocardiographic methods. Cardiac magnetic resonance (CMR) and its methods such as late gadolinium enhancement, and T1 mapping provides qualitative and quantitative assessment of interstitial myocardial fibrosis in hypertensive patients. Furthermore, CMR can provide differentiation of LVH between hypertensive patients and cardiomyopathies (hypertrophic or Fabry disease). Timely diagnosis of cardiac impairment and early treatment is essential because regression of LVH could be achieved with adequate treatment. Diffuse cardiac fibrosis in hypertensive patients might be an underlying mechanism that explains the increased cardiovascular morbidity and mortality in this population. Future longitudinal investigations are necessary to determine causal relationship between diffuse fibrosis and cardiovascular outcome in these patients. The aim of this review is to summarize the current knowledge regarding CMR techniques and their potential usage in patients with hypertensive heart disease.

     

Regression of left ventricular hypertrophy is a key goal of hypertension management

Left ventricular hypertrophy (LVH) in patients with hypertension is associated with an increased risk for many cardiovascular events and predicts a higher mortality rate. The pathogenesis of LVH is complicated. In addition to the hemodynamic burden (pressure or volume overload) and demographic factors, several trophic humoral factors, such as angiotensin II, aldosterone, endothelin, leptin, and catecholamines, may also contribute to the development and progression of LVH. Effective antihypertensive therapy can reverse LVH as well as prevent its development. Regression of LVH decreases subsequent cardiovascular morbidity and mortality. The commonly used drugs have various effects on LVH. Angiotensin receptor blockers and angiotensin-converting enzyme inhibitors seem most effective. Several new agents, including direct antifibrotic drugs, aldosterone blockade, vasopeptidase inhibitors, and endothelin receptor antagonists that more specifically target the underlying pathogenesis of LVH may provide us with innovative approaches to treat LVH.     

An evaluation of the therapeutic trials aimed at regression of ventricular hypertrophy in arterial hypertension]

Left ventricular hypertrophy (LVH) which is a mechanism of adaptation of the heart to hypertension (HT) may become a cardiovascular risk factor independent of the HT which has caused it. Causing the regression of LVH is thus one of the mid-term aims of antihypertensive therapy. Certain antihypertensive drugs are capable of producing an early and durable regression of LVH: methyldopa, beta-blockers, ACEI, calcium blockers. The effect of mass reduction is moderate or doubtful with diuretics, while it is nil or inconstant with vasodilators. The regression of LVH in HT raises various problems: 1) reliability of the measurement technique, 2) inter-individual and inter-drug variations, 3) favourable nature of regression, 4) preventive effect of regression against cardiovascular complications. Finally, in the light of recent studies it appears that early treatment of HT may prevent the onset of LVH.