糖尿病合并高血压的可能机制和降压药选择策略

糖尿病合并高血压使患者心、脑血管事件和终末期肾病的发病危险明显增加。本文简述了糖尿病合并高血压的可能机制,并对糖尿病合并高血压患者的降压药选择进行了复习。目前的总体认识为：血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体阻滞剂、钙通道阻滞剂对糖代谢和糖尿病本身的作用为中性,甚至可产生一定的有益作用;而利尿剂、β受体阻滞剂则可能对糖代谢产生不利影响,特别是当两者合用时,但现有的研究资料尚不能明确证实某一类型降压药具有明显的优越性,因此,无论使用何种药物,使患者的血压迅速、稳定地控制在130/80mmHg以下才是最重要的目标。     

某院2010～2012年抗高血压药的应用分析

目的了解我院抗高血压药的利用情况与趋势。方法对我院2010至2012年抗高血压药的种类、销售金额、用药频度等进行统计、分析。结果我院抗高血压药的销售金额呈逐年上升趋势。钙通道阻滞剂在三年中始终排在销售金额第一位,其次是血管紧张素Ⅱ受体阻滞剂和血管紧张素转换酶抑制剂。结论我院抗高血压药以钙通道阻滞剂、血管紧张素Ⅱ受体阻滞剂、血管紧张素转换酶抑制剂、β受体阻滞剂和利尿药为主,与国内外用药基本相符。钙通道阻滞剂、血管紧张素Ⅱ受体阻滞剂、血管紧张素转换酶抑制剂有广阔的用药前景。     

Antihypertensive drug therapy in patients with African ancestry

Blood pressure plays an important role in the development and progression of cardiovascular disease. Among hypertensive patients, those with African ancestry present with distinctive metabolic characteristics and cardiovascular profile. As a result, the need for individualized antihypertensive treatment strategy is of great importance. Lifestyle modifications as well as low sodium diet will play a major role in controlling blood pressure. The initiation of antihypertensive treatment with calcium channel blockers or diuretics is favored over angiotensin receptor blockers, angiotensin-converting enzyme inhibitors or β-blockers, provided no specific indications for the latter drugs are present. Moreover, the need for combination treatment often arises. As a result, the effective and safe hypertension management of patients with African ancestry is of critical importance for reducing cardiovascular morbidity and mortality.     

某高校社区门诊离退休教工抗高血压药的使用分析

目的了解和分析某社区门诊离退休教工抗高血压药的使用情况。方法抽查1 264例(2011年3月)门诊离退休高血压患者处方,详细统计及分析。结果 5大类抗高血压药中,钙拮抗药(CCB)使用率最高,达到51.91%,β-肾上腺素受体阻滞药(β-阻滞药)占14.49%,血管紧张素转化酶抑制药(ACEI)占9.22%,血管紧张素Ⅱ受体抑制药(ARB)占11.33%,利尿药占1.45%。采用单种抗高血压药治疗1 018例(占80.54%),联合使用2种或2种以上抗高血压药246例(占19.46%),利尿药联合使用率占13.82%。结论该社区门诊抗高血压药的种类及联合用药符合《中国高血压防治指南》的要求,基本合理规范,但抗高血压药物联合应用较少、利尿药的使用率偏低。     

临床常用降压药物的不良反应及安全对策

目的为高血压药物在临床中的安全使用提供参考。方法通过检索近10年国内临床治疗高血压的常见药物,选择利尿剂、β-受体阻滞剂、钙拮抗剂、ACEI和ARB中的一些代表药物进行典型不良反应的归纳分析,并提出相应的安全用药对策。结果临床治疗上考虑降压的同时应了解和掌握可能的不良反应与处理方法。结论重视药物在临床治疗中的不良反应是促进其安全使用的重要一环。     

我院慢性病门诊降压药物的应用情况分析

目的分析该院慢性病门诊抗高血压药物的使用情况。方法选取该院高血压门诊慢性病处方280张,分析应用降压药患者年龄分布,各类降压药用药频度(DDDs)排序及常用抗高血压药物DDDs及药物利用指数(DUI)。结果 280张处方中,男性患者处方136张(48.57%),女性患者处方144张(51.43%)。50～80岁患者229例,占患者总数的81.79%。高血压病患者降压药用药次数由高至低依次为钙拮抗剂(CCB)、血管紧张素Ⅱ受体拮抗剂(ARB)、β-受体阻滞剂(β-RB)、血管紧张素转化酶抑制剂(ACEI)、利尿剂及α-受体阻滞剂(α-RB)。常用抗高血压药物DDDs居前3位的为厄贝沙坦、氨氯地平(安内真)和替米沙坦。所有常用抗高血压药DUI均<1。结论该院慢性病门诊降血压药物的使用情况比较合理,应继续加强处方审查和药学监护,真正做到安全、有效、经济地合理用药。     

Strategies to prevent type 2 diabetes

Type 2 diabetes mellitus is a public health problem of epidemic proportions and its prevalence is on the rise. The typical American born today has a one in three chance of developing type 2 diabetes. This diagnosis is associated with an adverse cardiovascular prognosis and is considered the risk equivalent of established coronary disease. Many risk factors, including the metabolic syndrome, have been implicated in its development. Even in high-risk individuals, type 2 diabetes is a preventable disease. Diet and exercise have been consistently shown to decrease the incidence of diabetes in large randomized controlled studies. Additionally, new-onset diabetes was reduced by several oral pharmacologic anti-diabetic agents including metformin, acarbose and troglitazone in randomized trials which studied patients with impaired glucose tolerance. More interestingly, multiple large prospective studies have also reported a reduction in the development of type 2 diabetes in patients treated with anti-hypertensive agents, predominantly angiotensin converting enzyme inhibitors and angiotensin receptor blockers. In this review, we will discuss some of these important trials and the speculative mechanisms whereby those medications prevent type 2 diabetes. Such observations, if proven to be true, may represent preventive strategies which can be considered in patients with pre-diabetic conditions such as the metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure or other risks for the development of type 2 diabetes.     

New advances in the pharmacological management of chronic heart failure

The management of heart failure has evolved in parallel with advances in the understanding of the disease process. Inotropes and diuretics are used to combat pump failure and fluid overload. While no convincing data has emerged regarding the long-term safety of inotropes, new exciting data concerning the role of diuretics, especially aldactone, has led to a renewed interest in this class of drug therapy. Angiotensin converting enzyme inhibitors (ACE inhibitors) were noted to not only affect symptomatology but also decrease mortality by interfering with the renin-angiotensin-aldosterone system. Recent research has focused on more complete blockade of the renin-angiotensin system than that achieved with ACE inhibitors alone with the addition of direct angiotensin II receptor blockers. This new class of drugs may become not only a reasonable alternative to ACE inhibitors in patients intolerant of the drug but also a possible addition to ACE inhibitors in the battle to prevent progression of remodelling and disease. β-blockers are the most exciting new class of drugs used to combat heart failure. They appear not only to combat the remodelling process that occurs in the progression of disease but also other pathological events such as apoptosis and cellular oxidation. New medical therapies currently being investigated include novel agents such as endothelin antagonists, natriuretic peptides, vasopressin antagonists and anticytokine agents - all part of a new era in drug management of heart failure that has evolved with continued advances in the understanding of chronic heart failure (CHF).     

新型口服抗高血压药阿利克伦的临床药理学研究进展

肾素直接抑制剂阿利克伦是一种新型、安全、有效的口服抗高血压药物,并且具有肾脏保护、减少左心窒肥厚等作用,可以单用或者与ACE抑制剂(如雷米普利)、Aug Ⅱ受体阻滞剂(如缬沙坦)和噻嗪类利尿剂等降压药物联合使用,降压作用具有剂量依赖性,病人耐受性良好.     

Strategies to prevent type 2 diabetes

ABSTRACT

Type 2 diabetes mellitus is a public health problem of epidemic proportions and its prevalence is on the rise. The typical American born today has a one in three chance of developing type 2 diabetes. This diagnosis is associated with an adverse cardiovascular prognosis and is considered the risk equivalent of established coronary disease. Many risk factors, including the metabolic syndrome, have been implicated in its development. Even in high-risk individuals, type 2 diabetes is a preventable disease. Diet and exercise have been consistently shown to decrease the incidence of diabetes in large randomized controlled studies. Additionally, new-onset diabetes was reduced by several oral pharmacologic anti-diabetic agents including metformin, acarbose and troglitazone in randomized trials which studied patients with impaired glucose tolerance. More interestingly, multiple large prospective studies have also reported a reduction in the development of type 2 diabetes in patients treated with anti-hypertensive agents, predominantly angiotensin converting enzyme inhibitors and angiotensin receptor blockers.

In this review, we will discuss some of these important trials and the speculative mechanisms whereby those medications prevent type 2 diabetes. Such observations, if proven to be true, may represent preventive strategies which can be considered in patients with pre-diabetic conditions such as the metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure or other risks for the development of type 2 diabetes     

Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: fact or fiction

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and beta-blockers, or the newer agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. Beta-blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine-induced nephrotoxicity. When compared with beta-blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long-term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to beta-blockers, diuretics, and ACE inhibitors.     

Pharmacological, immunological, and gene targeting of the renin-angiotensin system for treatment of cardiovascular disease

Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not reduce cardiovascular disease risks to the levels in normotensive persons. Only two drug classes that inhibit or antagonize portions of the renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT(1) receptor) blockers, have protective and beneficial effects unrelated to the degree of blood pressure reduction. These drugs may prevent the blood pressure related functional and structural abnormalities of the cardiovascular system and reduce the end organ-damage. The first part of this review presents the components of the RAS, biological actions of angiotensin peptides, and the functions of the enzymes that generate and metabolize angiotensins, including the likely effect of manipulating them. Special attention is devoted to renin, ACE, ACE2, chymase, and neprilysin. The second part of this review presents the rationale for targeting the RAS, based on clinical studies of the ACE inhibitors and AT(1) receptor blockers. Finally, we present the investigational agents acting on the RAS that have a potential for clinical usage, and give the perspective of pharmacological, immunological and gene targeting of the RAS for treatment of cardiovascular disease.     

Plasma renin activity-guided strategy for the management of hypertension

Despite the wide array of antihypertensive agents and the availability of national guidelines regarding treatment for hypertension, the disease remains uncontrolled in nearly 50% of affected patients. Furthermore, the number of patients with resistant hypertension continues to increase. For patients with resistant hypertension, the American Heart Association has advocated for clinical studies to determine appropriate pharmacologic treatment strategies. One proposed strategy involves ambulatory measurement of plasma renin activity (PRA) to guide the selection of antihypertensive therapy. Patients with low PRA would be prescribed natriuretic volume-mediated therapies (e.g., diuretics and calcium channel blockers), whereas those with high PRA would receive antirenin system therapies (e.g., β-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers). This review focuses on the principles of PRA-guided therapy, its historical development, alternative approaches to classifying patients into categories of response to antihypertensive agents, and recent data supporting the use of plasma renin activity-guided hypertension management.     

药物治疗顽固性高血压的研究进展

在高血压患者中,有15％～20％属于顽固性高血压。顽固性高血压具有更高的心血管事件的风险,给患者造成的危害也更严重。临床治疗顽固性高血压,需要结合患者的自身情况,选择不同的降压药联合用药。目前较为常用方案为血管紧张素转换酶抑制剂（或血管紧张素II受体阻滞剂）、钙拮抗剂和噻嗪类利尿剂3种药物组合,或由扩血管药、减慢心率药和利尿剂组合。本文综述了治疗顽固性高血压的联合用药方案和药物选择等方面的研究进展,为更好地治疗该病提供借鉴。     

Pharmacogenetics of chronic cardiovascular drugs: applications and implications

Cardiovascular disease continues to be a tremendous worldwide problem, and drug therapy is a major modality to attenuate its burden. At present, conditions such as hypertension, dyslipidaemia and heart failure are pharmacologically managed with an empirical trial-and-error approach. However, it has been suggested that this approach fails to adequately address the therapeutic needs of many patients, and pharmacogenetics has been offered as a tool to enhance patient-specific drug therapy. This review outlines pharmacogenetic studies of common cardiovascular drugs, such as diuretics, β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins and warfarin, ultimately highlighting considerations for future research and practice.     

The Effect of Antihypertensive Agents on New-Onset Diabetes Mellitus

Recent large hypertension trials have shown great differences in incidence of new-onset diabetes mellitus among patients receiving different antihypertensive drug therapies. The incidence of diabetes is unchanged or increased by the use of thiazide diuretics and beta-adrenoceptor antagonists (beta-blockers) and unchanged or decreased by ACE inhibitors, calcium channel blockers (CCBs), and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers). Recent results from ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) showed superiority of the 'new' combination of CCBs and ACE inhibitors over the 'old' or 'conventional' combination of beta-blockers and diuretics. In this review, the results from some of the large hypertension trials are discussed, and the hypotheses on how different antihypertensive drug regimens can affect glucose homeostasis are considered. The question now is whether the results from these recent trials should affect the choice of antihypertensive treatment, particularly for special groups. However, the key goal is still to reduce BP, and this usually requires combinations of drugs.     

Factors influencing hepatic metabolism of antihypertensive drugs: impact on clinical response

Introduction: Although main antihypertensive drugs are able to efficiently reduce blood pressure, only a third of treated hypertensive patients achieve optimal blood pressure control. Extensive interpatient variability on drug metabolism and oral disposition of blood pressure lowering drugs can contribute to this failure in hypertension management.

Areas covered: The aim of the present review is to update the knowledge on the features of hepatic metabolism of the main antihypertensive agents, including β-blockers, calcium channel blockers, angiotensin receptor blockers, and angiotensin converting enzyme inhibitors. The factors that contribute to the large interindividual variability of main antihypertensive drugs are also covered.

Expert opinion: The variability of plasma concentration of antihypertensive drugs due to the involvement of hepatic metabolism can contribute to the inadequate control of blood pressure in the daily clinical practice. Genotype screening of specific hepatic drug-metabolizing enzymes may contribute to optimize dose selection and to increase the rate of blood pressure control in patients treated with specific β-blockers, calcium channel blockers, and angiotensin receptor blockers.     

The Role of Angiotensin Receptor Blocker and Calcium Channel Blocker Combination Therapy in Treating Hypertension

Hypertension remains a significant health problem, affecting approximately 30% of the US population. Of these, only 36.8% have BP controlled to recommended levels of <140/90mmHg for uncomplicated hypertension and <130/80 mmHg for patients with diabetes mellitus or renal disease. For those with uncontrolled hypertension, the risk of diabetes, renal disease, stroke, and cardiovascular disease is increased. Therapeutic options for the treatment of hypertension include several major classes of drugs: diuretics, ß-adrenoceptor antagonists (ß-blockers), ACE inhibitors, angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), renin inhibitors, calcium channel blockers, and central sympatholytics, alone or in combination. Guidelines recommend thiazide diuretics as preferred first-line monotherapy. However, only 50% of patients will respond adequately to this therapy and the rest will require two or more antihypertensive agents to achieve BP goals. Clinical evidence demonstrates that some drugs have advantages when used in combination rather than as monotherapy. Drugs that block the renin-angiotensin-aldosterone system not only provide BP control but may also provide vascular protection and are metabolically neutral. This is a concise review of the safety and efficacy of ARBs in combination with amlodipine for the treatment of hypertension, with focus on the telmisartan-amlodipine combination. A MEDLINE search of the English literature from 2006 to 2009 of amlodipine in combination with ARBs revealed six publications, which are included in this review.     

Regression of increased left ventricular mass by antihypertensives.

Left ventricular hypertrophy (LVH) is both a target organ response to chronic arterial hypertension and a disorder that may be responsible for cardiovascular events. Although an increase in ventricular wall thickness may initially be compensatory and decrease wall stress, numerous studies have indicated that LVH is associated with a reduction in coronary flow reserve, diastolic and systolic ventricular dysfunction, and ventricular arrhythmias, all of which predispose to morbid cardiovascular events, including acute coronary syndromes, congestive myocardial failure, and sudden death. Reduction in LVH has been accomplished with beneficial effects on diastolic function and ventricular arrhythmias, without pressure-induced deterioration in systolic or diastolic function. Although therapy with diuretics and vasodilators effectively lowers arterial pressure, these therapies are not usually associated with significant regression of LVH. Calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, beta-adrenergic blockers, central adrenergic blocking agents, and possibly alpha-adrenergic blockers and diuretics with vasodilatory properties are associated with reductions in LV mass. However, studies are still needed to determine the relative effects of various antihypertensive therapies on LVH regression, coronary flow reserve, ventricular function, ventricular ectopy, and most importantly, on protection against major cardiac morbidity and mortality inherent to LVH.     

Quality of life in hypertension management using olmesartan in primary care

Objective: Differences in quality of life (QoL) using antihypertensive drugs may account for differences in compliance, persistence and blood pressure control. As this is the prerequisite for cardiovascular risk reduction, QoL was investigated using highly tolerable drugs (such as olmesartan). Research design/methods: The non-interventional study was carried out in 4252 primary care patients with 6 weeks of follow up. Documentation of patient characteristics included concomitant diseases and antihypertensive medication, blood pressure, pulse pressure, pulse rate and evaluation of QoL using the SF-12 questionnaire. Comparison of data at 6 weeks after adding or switching to olmesartan treatment (median dose: 20 mg) with baseline values. Main outcome measures: Patients had mild-to-moderate hypertension, 52.6% of whom were male and the mean age was 60.5 ± 11.9 years. Dyslipidaemia (38.3%), diabetes (20.9%) and coronary heart disease (16.4%) were the most frequent concomitant diseases. After 6 weeks, blood pressure was reduced by -22.8 ± 14.1/-11.5 ± 8.3 mmHg (p < 0.001 versus baseline). All items of the SF-12 questionnaire and both sum scores improved over the course of treatment (p < 0.001 versus baseline), and were well compatible with non-hypertensive controls. Improvements were higher when switching from α-blockers, calcium channel blockers, β-blockers, diuretics and angiotensin-converting enzyme inhibitors as compared with angiotensin II type 1 receptors blockers (ARBs), in particular on the mental health scale (p < 0.001). Adverse events were rare (0.66%), with dizziness (n = 8; 0.19%) being the most frequent. Conclusions: As was shown in the current study, patients on olmesartan treatment not only achieve adequate blood pressure control but also experienced a substantial improvement of QoL. This may contribute to long-term blood pressure control using ARBs.