High blood pressure and diabetes mellitus: are all antihypertensive drugs created equal?

OBJECTIVE: To analyze the available data to assess the benefits of antihypertensive therapy in hypertensive patients with diabetes mellitus. METHODS: A MEDLINE search of English-language articles published until June 1999 was undertaken with the use of the terms diabetes mellitus, hypertension or blood pressure, and therapy. Pertinent articles cited in the identified reports were also reviewed. Included were only prospective randomized studies of more than 12 months' duration that evaluated the effect of drug treatment on morbidity and mortality in diabetic hypertensive patients. We estimated the risk associated with combination of diabetes mellitus and hypertension and the effect of treatment on morbidity and mortality. RESULTS: The coexistence of diabetes mellitus doubled the risk of cardiovascular events, cardiovascular mortality, and total mortality in hypertensive patients (approximate relative risk of 1.73-2.77 for cardiovascular events, 2.25-3.66 for cardiovascular mortality, and 1.73-2.18 for total mortality). Intensive blood pressure control to levels lower than 130/85 mm Hg was beneficial in diabetic hypertensive patients. All 4 drug classes-diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium antagonists-were effective in reducing cardiovascular events in diabetic hypertensive patients. In elderly diabetic patients with isolated systolic hypertension, calcium antagonists reduced the rate of cardiac end points by 63%, stroke by 73%, and total mortality by 55%. In more than 60% of diabetic hypertensive patients, combination therapy was required to control blood pressure. CONCLUSIONS: Intensive control of blood pressure reduced cardiovascular morbidity and mortality in diabetic patients regardless of whether low-dose diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, or calcium antagonists were used as a first-line treatment. A combination of more than 1 drug is frequently required to control blood pressure and may be more beneficial than monotherapy.     

The association of hypertension and diabetes: prevalence, cardiovascular risk and protection by blood pressure reduction

Diabetes and hypertension frequently coexist, and their combination provides additive increases in the risk of life-threatening cardiovascular events. Recent guidelines agree on the need for early, aggressive reduction of blood pressure, with a goal of <130/80 mmHg, in patients with diabetes. The mechanism that underpins the increased sensitivity of diabetic subjects to hypertension is not known, but may involve impaired autoregulation or attenuated nocturnal decrease of blood pressure. All classes of antihypertensive agents are effective in reducing blood pressure in diabetic subjects, and all show evidence of a concomitant reduction in cardiovascular risk. Although there is some evidence that agents that interrupt the renin-angiotensin system (RAS) provide greater protective effects, the data are not conclusive. However, most diabetic subjects will require combination therapy to reach goal blood pressure. Antihypertensive drugs can also significantly influence the probability that otherwise healthy individuals will develop metabolic syndrome or type 2 diabetes. While diuretics and betablockers have a prodiabetic effect, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may prevent diabetes more effectively than the metabolically neutral calcium channel blockers. Given that diabetes is an important cardiovascular risk factor, there is the potential for reductions in risk due to reduced blood pressure to be offset by an increased risk due to the development of diabetes. Such concerns should be considered in the selection of antihypertensive therapy.     

Why is blood pressure so hard to control in patients with type 2 diabetes?

Resistance to antihypertensive drugs is common in hypertensive patients with type 2 diabetes. This is unfortunate because hypertension is one of the most important risk factors for development of cardiovascular events, and the goal blood pressure level is set lower in diabetic subjects than in nondiabetic subjects. Previous outcome trials in diabetic subjects have mainly focused on end points such as microalbuminuria or the incidence of cardiovascular events rather than on reduction of blood pressure; some reports, however, have suggested mechanisms for the drug resistance. These include several clinical conditions known to be associated with difficulty in reducing blood pressure specifically in diabetes mellitus: change in the renin-angiotensin system and chymase, volume overload, central sympathetic hyperactivity, sleep apnea, secondary hypertension, pseudoresistance (white coat hypertension), and poor compliance related to subclinical depression. In this review, the authors focus on the mechanisms of resistance to antihypertensive therapy (particularly for monotherapy with either angiotensin-converting enzyme inhibitors or angiotensin II antagonists) in the treatment of diabetic hypertension.     

Diabetes and Hypertension: Pathogenesis,Prevention and Treatment

Hypertension occurs in approximately 30% of patients with type 1 diabetes and from 50 to 80% of patients with type 2 diabetes. Although the pathogenesis of hypertension is distinct in each type, hypertension markedly enhances the already high risk of cardiovascular and renal disease in types 1 and 2 and implications for treatment are similar in both. The threshold for blood pressure treatment in diabetic patients is generally agreed to be 140/90 mm/hg with a target BP of < 130/80. So‐called “lifestyle modifications” play an important role in therapy, particularly in type 2 patients, by decreasing blood pressure and improving other risk factors for cardiovascular disease. Indeed non‐pharmacologic interventions have been demonstrated to prevent the development of type 2 diabetes in patients at high risk to develop the disease. Aggressive anti‐hypertensive drug treatment is warranted given the high risk associated with the combination of diabetes and hypertension and the demonstrated effectiveness of anti‐hypertensive treatment in reducing cardiovascular morbidity and mortality in this group of patients. ACE inhibitors and ARBs are the cornerstones of pharmacologic management, in no small part because of the renoprotective effects of these agents in antagonizing the development and progression of diabetic renal disease. Multiple agents, including diuretics, will usually be required to attain target blood pressure levels.     

ESH-ESC Guidelines for the Management of Hypertension

The following is a brief statement of the 2003 European Society of Hypertension (ESH)-European Society of Cardiology (ESC) guidelines for the management of arterial hypertension.The continuous relationship between the level of blood pressure and cardiovascular risk makes the definition of hypertension arbitrary. Since risk factors cluster in hypertensive individuals, risk stratification should be made and decision about the management should not be based on blood pressure alone, but also according to the presence or absence of other risk factors, target organ damage, diabetes, and cardiovascular or renal damage, as well as on other aspects of the patient's personal, medical and social situation. Blood pressure values measured in the doctor's office or the clinic should commonly be used as reference. Ambulatory blood pressure monitoring may have clinical value, when considerable variability of office blood pressure is found over the same or different visits, high office blood pressure is measured in subjects otherwise at low global cardiovascular risk, there is marked discrepancy between blood pressure values measured in the office and at home, resistance to drug treatment is suspected, or research is involved. Secondary hypertension should always be investigated.The primary goal of treatment of patient with high blood pressure is to achieve the maximum reduction in long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible factors identified, including smoking, dislipidemia, or diabetes, and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure per se. On the basis of current evidence from trials, it can be recommended that blood pressure, both systolic and diastolic, be intensively lowered at least below 140/90 mmHg and to definitely lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg in diabetics.Lifestyle measures should be instituted whenever appropriate in all patients, including subjects with high normal blood pressure and patients who require drug treatment. The purpose is to lower blood pressure and to control other risk factors and clinical conditions present.In most, if not all, hypertensive patients, therapy should be started gradually, and target blood pressure achieved progressively through several weeks. To reach target blood pressure, it is likely that a large proportion of patients will require combination therapy with more than one agent. The main benefits of antihypertensive therapy are due to lowering of blood pressure per se. There is also evidence that specific drug classes may differ in some effect or in special groups of patients. The choice of drugs will be influenced by many factors, including previous experience of the patient with antihypertensive agents, cost of drugs, risk profile, presence or absence of target organ damage, clinical cardiovascular or renal disease or diabetes, patient's preference.     

The choice of antihypertensive drugs in patients with diabetes: angiotensin II and beyond

Affecting over 16 million individuals, diabetes mellitus is among the leading causes of mortality in the United States. Hypertension is a common finding among diabetic patients and increases their morbidity and mortality. Control of blood pressure in this population has been shown to improve outcomes. Recent randomized trials have proven the benefit of lower blood pressure goals in the treatment of hypertensive patients as compared with nondiabetic patients. Randomized controlled trials have also demonstrated that the selection of the antihypertensive agent used to treat hypertension in diabetic patients is as important as the reduction of blood pressure levels to the recommended levels. In this article, we first focus on the importance of the renin angiotensin system in the development of diabetic complications, and then we review the results of the recent studies that have had a major impact on the treatment of hypertension in diabetes.     

Treatment of hypertension in patients with diabetes: lessons from recent trials

Hypertension plays a critical role in causing a high rate of cardiovascular events in patients with diabetes mellitus. Large trials show that lowering blood pressure in the patient with diabetes who has hypertension has profoundly favorable effects. This review discusses recent trials to answer the question of how low patients' blood pressure should go and which agents should be used to achieve this goal. The National Institutes of Health's guidelines, published in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, call for a blood pressure goal of <130/85 mmHg in patients with diabetes. Based on data from the recent trials, an even lower blood pressure of <130/80 mmHg in patients with diabetes and hypertension appears to be appropriate. Observational studies show that the lowest cardiovascular event rate is observed in patients with diabetes whose systolic blood pressure is <120 mmHg. Thus, goal blood pressure in patients with diabetes who have hypertension may need to be revised lower, to <120/80 mmHg. In patients with overt proteinuria of 1 g/d or more, mean arterial pressure of <92 mmHg is recommended. Available evidence justifies the use of angiotensin-converting enzyme (ACE) inhibitors as first-line agents and angiotensin receptor blockers in those patients who are intolerant to ACE inhibitors. Because the blood pressure goal is lower in patients with diabetes who are hypertensive, these patients require the use of multiple agents. Diuretics or long-acting calcium channel blockers are logical second choices because of their synergistic blood pressure reduction effect observed with ACE inhibitors. Alpha-blockers should be used with caution, however. In patients with renal disease, loop diuretics may be required to reduce sodium and volume overload and to improve blood pressure control.     

Diabetes mellitus and hypertension.

Diabetes mellitus and hypertension are common diseases that coexist at a greater frequency than chance alone would predict. Hypertension in the diabetic individual markedly increases the risk and accelerates the course of cardiac disease, peripheral vascular disease, stroke, retinopathy, and nephropathy. Our understanding of the factors that markedly increase the frequency of hypertension in the diabetic individual remains incomplete. Diabetic nephropathy is an important factor involved in the development of hypertension in diabetics, particularly type I patients. However, the etiology of hypertension in the majority of diabetic patients cannot be explained by underlying renal disease and remains "essential" in nature. The hallmark of hypertension in type I and type II diabetics appears to be increased peripheral vascular resistance. Increased exchangeable sodium may also play a role in the pathogenesis of blood pressure in diabetics. There is increasing evidence that insulin resistance/hyperinsulinemia may play a key role in the pathogenesis of hypertension in both subtle and overt abnormalities of carbohydrate metabolism. Population studies suggest that elevated insulin levels, which often occurs in type II diabetes mellitus, is an independent risk factor for cardiovascular disease. Other cardiovascular risk factors in diabetic individuals include abnormalities of lipid metabolism, platelet function, and clotting factors. The goal of antihypertensive therapy in the patient with coexistent diabetes is to reduce the inordinate cardiovascular risk as well as lowering blood pressure.     

Blood pressure targets in type 2 diabetes. Evidence against or in favour of an aggressive approach

When associated with high blood pressure, type 2 diabetes mellitus is characterised by a high risk of adverse cardiovascular (CV) and renal outcomes. However, both can be effectively reduced by antihypertensive treatment. Current guidelines on the treatment of hypertension emphasize the need to effectively treat high blood pressure in diabetic individuals, but their recommendations differ in terms of the optimal target blood pressure value to aim for in order to maximise CV and renal protection. In some guidelines the recommended target blood pressure values are <140/90 mmHg (systolic/diastolic), whereas in others, blood pressure values close or even less than 130/80 mmHg are recommended. This paper will discuss the evidence for and against a conservative or more aggressive blood pressure target for treated diabetic hypertensive individuals based on the evidence provided by randomised trials, trial meta-analyses and large observational studies. Based on the available evidence, it appears that blood pressure targets will probably have to be lower than <140/90 mmHg, and that values approaching 130/80 mmHg should be recommended. However, evidence in favour of even lower systolic values, i.e. <130 mmHg, is limited and is definitively against a reduction to <120 mmHg.     

Management of high-risk hypertensive patients with diabetes: potential role of angiotensin II receptor antagonists

Uncontrolled hypertension leads to an increased risk of cardiovascular disease and stroke. Hypertensive patients with concomitant type 2 diabetes are at even greater risk of cardiovascular complications; also, this high-risk patient population is at increased risk of renal disease and, ultimately, renal failure. Prospective morbidity and mortality trials have demonstrated that tight blood pressure control improves the cardiovascular prognosis and provides target organ protection. Current treatment guidelines recommend a target blood pressure of <130/85 mm Hg for patients with hypertension and diabetes. Angiotensin II (A-II), a major component of the renin-angiotensin system, plays an essential role in the pathophysiology of hypertension and diabetes-related renal disease. Currently, the treatment of choice for hypertensive patients with diabetes is angiotensin-converting enzyme (ACE) inhibition, but most of the data are limited to patients with type 1 diabetes. Although ACE inhibition is clearly a mechanism for blocking A-II formation, inhibition at this site may not be complete, as alternate pathways exist for A-II formation. Thus, for interrupting the renin-angiotensin system, A-II receptor antagonists theoretically provide advantages over ACE inhibitors in that they directly inhibit A-II by binding to the AT₁ receptor subtype. The objectives of this review are to: 1) provide an overview of the associated risk of cardiovascular complications with concomitant hypertension and diabetes; 2) demonstrate the cardiovascular benefits of effective blood pressure control in this patient population; 3) review the current treatment guidelines for managing high-risk hypertensive patients; and 4) discuss major, ongoing clinical studies with A-II receptor antagonists in patients with concomitant hypertension, type 2 diabetes, and renal disease.     

Excess mortality associated with diuretic therapy in diabetes mellitus.

OBJECTIVE. To determine whether the high mortality among diabetic patients receiving treatment for hypertension can be explained by associated risk factors or must be attributed to a deleterious effect of antihypertensive treatment. DESIGN. Cohort analytic study with a median follow-up of 4.5 years. SETTING. Outpatients with diabetes and severe retinopathy who were enrolled in a multicenter, randomized clinical trial of laser treatment to prevent blindness had ophthalmologic examinations every 4 months and annual medical examinations that included measurement of blood pressure and recording of anti-hypertensive treatment. Only 5.5% of the patients were unavailable for follow-up. When a patient died, the circumstances surrounding the death were reviewed and classified by a mortality review committee. PARTICIPANTS.--There were 759 participants in the study; they were white, were aged 35 to 69 years, and had normal serum creatinine levels at the baseline examination. MEASUREMENTS AND MAIN RESULTS.--Patients were classified into five groups according to information recorded at the baseline and first annual follow-up examinations: normotensive (diastolic blood pressure less than 90 mm Hg), untreated hypertensive, hypertensive treated by diuretics alone, hypertensive treated by other agents alone, and hypertensive treated by both agents. Cardiovascular mortality was higher in patients treated for hypertension than in patients with untreated hypertension. The excess was primarily found in patients treated with diuretics alone, although that group had the lowest blood pressure with treatment. After adjusting for differences in risk factors, cardiovascular mortality was 3.8 times higher in patients treated with diuretics alone than in patients with untreated hypertension (P less than .001). CONCLUSIONS.--In individuals with diabetes, intervention with diuretics to reduce hypertension is associated with excess mortality. Until there is a clinical trial showing a beneficial effect of diuretic treatment in diabetic patients, there is urgent need to reconsider its continued usage in this population.     

Persistent remodeling of resistance arteries in type 2 diabetic patients on antihypertensive treatment

We hypothesized that resistance arteries from diabetic patients with controlled hypertension have less remodeling than vessels from untreated hypertensive subjects. Eight normotensive subjects (aged 44+/-3 years, 3 men; values are mean+/-SEM), 19 untreated hypertensive subjects (46+/-2 years, 9 men), and 23 hypertensive subjects with type 2 diabetes mellitus under antihypertensive treatment (58+/-1 years, 15 men) were studied. Resistance arteries dissected from gluteal subcutaneous tissue were assessed on a pressurized myograph. Most diabetic patients (70%) were being treated with angiotensin-converting enzyme inhibitors. Although systolic blood pressure was still above the normotensive range in these patients (144+/-2 versus 150+/-3 mm Hg in hypertensive and 114+/-4 mm Hg in normotensive subjects), diastolic blood pressure was well controlled (83+/-2 mm Hg) and significantly lower compared with that in untreated hypertensives (100+/-1 mm Hg; P<0.001) but higher than in normotensives (76+/-3 mm Hg; P<0.05). Thus, pulse pressure was higher in diabetic patients (P<0.05). The media-to-lumen ratio of resistance arteries was greater in hypertensives (0.083+/-0.002) compared with normotensive controls (0.059+/-0.003; P<0.05) and was even higher in diabetic hypertensive subjects (0.105+/-0.004; P<0.001 versus normotensive controls). The medial cross-sectional area was greater in diabetic and hypertensive patients compared with normotensive controls (P<0.001). Acetylcholine-induced relaxation was impaired in vessels from hypertensive patients and from patients with both diabetes mellitus and hypertension (P<0.05 versus normotensive controls), whereas endothelium-independent vasorelaxation was similar in all groups. Despite effective antihypertensive treatment, resistance arteries from hypertensive diabetic patients showed marked remodeling, greater than that of vessels from untreated, nondiabetic, hypertensive subjects, in agreement with the high cardiovascular risk of subjects suffering from both diabetes and hypertension.     

Blood pressure control, microalbuminuria and cardiovascular risk in Type 2 diabetes mellitus.

Type 2 (noninsulin-dependent) diabetes mellitus (DM) affects about 3% of the UK population. Diabetes often coexists with a cluster of other potent cardiovascular risk factors, including hypertension, dyslipidaemia and increased tendency for thrombosis, and increases the risk of early death from cardiovascular causes by about threefold. Microalbuminuria or proteinuria also may be present, further increasing the risk of cardiovascular mortality. Cardiovascular risk factors must be treated aggressively in patients with Type 2 diabetes and control of blood pressure at 140/85 mm Hg or lower is a priority. The management of hypertension in patients from some ethnic groups demands special consideration because they have a high incidence of diabetes and hypertensive complications. Patients must be urged to adopt appropriate lifestyle changes in the first instance but additional drug treatment for hypertension is usually required. All the major classes of antihypertensive agents lower blood pressure in Type 2 diabetic patients but have different effects on metabolic risk factors in different ways. Low-dose thiazide diuretics, beta-blockers, calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk. Individually, the effects of low-dose thiazide diuretics and beta-blockers on glucose and lipid metabolism is clinically insignificant, though in combination much larger metabolic effects are seen. ACE inhibitors and calcium channel blockers have no, or small, beneficial effects on glucose and lipid metabolism, while the greater beneficial effects of alpha1-blockers on lipid profiles may render them especially useful in the Type 2 diabetic patient. Long-acting calcium-channel blockers and ACE inhibitors protect renal function and are suitable as first line therapy in patients with microalbuminuria or proteinuria. Until results from the current batch of randomized, placebo-controlled trials comparing different classes of antihypertensive agents are available, the choice of antihypertensive agent is difficult. Addressing overall cardiovascular risk factors, rather than hypertension alone, is essential in the management of the hypertensive Type 2 diabetic patient.     

Masked hypertension in adults

A body of evidence indicates that masked hypertension is a significant predictor of cardiovascular disease, but how to identify these patients is still a matter of dispute. Data obtained in several cross-sectional studies have demonstrated that masked hypertension is associated with increased left ventricular mass index and carotid intima-media thickness, and impaired large artery distensibility. Furthermore, in longitudinal studies, masked hypertension was a strong predictor of cardiovascular morbidity and mortality. Several factors that can selectively raise ambulatory blood pressure increase the likelihood of having masked hypertension. These include younger age, smoking, alcohol use, contraceptive use in women, sedentary habits and central obesity. In addition, masked hypertension is more common in individuals with high-normal clinic blood pressure or transiently elevated blood pressure. Increased reactivity to daily life stressors and behavioural factors are other important predictors of masked hypertension. In clinical practice, masked hypertension should be searched for in individuals who are more likely to have this condition or are at increased risk of cardiovascular events including those with coronary, cerebrovascular or kidney disease, patients with diabetes and individuals with a high cardiovascular risk profile. To determine whether the use of ambulatory blood pressure monitoring is cost-effective in these individuals, further research is needed.     

Diagnosis and management of hypertension in obesity

Cardiovascular risk in a patient with obesity hypertension increases with the extent of risk factor clustering. It is therefore important to determine the global risk of a patient with hypertension rather than to focus solely on blood pressure. Every hypertensive should be screened for other than blood pressure risk factors, target organ damage and concomitant diseases or accompanying clinical conditions. Assessment of blood pressure and target organ damage might be more difficult in obese hypertensives than in normal-weight patients. Intensive lifestyle interventions can reduce weight, and decrease blood pressure and cardiovascular risk in obese hypertensive patients. Current guidelines do not provide specific recommendation for pharmacological management of the hypertensive patients with obesity. Recent trials have consistently shown that therapy involving beta-blockers and diuretics may induce more new-onset diabetes compared with other combination therapies. Several lines of evidence suggest that anti-hypertensive agents that block the renin-angiotensin system may be especially beneficial in treating obese hypertensive patients. Hypertension management in obese individuals is complicated by poorer response to treatment, and the increased need for multiple medications. It is important to consider obstructive sleep apnoea in the differential diagnosis of hypertensive patients who respond poorly to combination therapy with anti-hypertensive medications.     

Optimizing target-organ protection in patients with diabetes mellitus: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers?

High blood pressure in the setting of type 1 and type 2 diabetes is commonly associated with the earlier development of target-organ damage, including cardiovascular and cerebrovascular disease and progressive renal insufficiency. The major goal of treating high blood pressure in this population is to prevent or reduce the likelihood of targetorgan damage. The treatment goal for high blood pressure, therefore, has to be defined based on optimal means of preventing cardiovascular and renal events. The reduction of high blood pressure with pharmacologic therapy is associated with reduction of cardiovascular events, renal disease, and associated mortality. However, many questions remain. Some of the basic and important questions include the following: What should be the goal of treated blood pressure in the diabetic, and are there preferred agents that should be used in the hypertensive diabetic population? How do angiotensin-converting enzyme inhibitors and angiotensin receptor blockers fit in? Are there advantages of one class over the other? The goal of this review is to summarize the recent clinical trial findings and try to provide recommendations based on the evidence of these trials to help the clinician better choose blood pressure goals and treatment strategies in the diabetic population.     

Leitliniengerechte Differenzialtherapie der Hypertonie

The goal of antihypertensive therapy is to lower blood pressure and, by doing so, to decrease cardiovascular risk. Life style changes and drugs are available for the treatment of hypertensive patients. In order to reach the target blood pressure, most patients with hypertension need drug treatment in addition to life style changes. In all hypertensive patients, the target blood pressure is <140/90 mmHg. In patients with diabetes mellitus, with chronic renal failure as well as in patients with complications of hypertension and, thereby a very high cardiovascular risk, the target blood pressure is <130/80 mmHg. Diuretics, beta-blockers, calcium antagonists, ACE-inhibitors and angiotensin receptor blockers are the drugs of first choice in the treatment of hypertension. The selection among these drug classes has to consider probable side effects as well as accompanying diseases and complications of hypertension. One should also take into account that most of the beneficial effects of antihypertensive therapy is due to the decrease of blood pressure per se and that the majority of hypertensive patients require the combination of two or more antihypertensive drugs in order to reach the target blood pressure.     

Long-term safety of antihypertensive therapy

Lowering blood pressure (BP) in hypertensive patients reduces morbidity and mortality. However the long-term safety of some antihypertensive agents was a matter of concern. Diuretic, the gold standard treatment in hypertension may impair glucose tolerance and thereby accelerate the development of diabetes mellitus. It was also associated with increased cardiovascular mortality in diabetic patients. However, recent evidence showed that low-medium dose of thiazide diuretic especially when given in combination with potassium sparing agent is effective in reducing BP and cardiovascular morbidity and mortality. Beta blockers are less effective than other antihypertensive agents in the elderly. Therefore they may be appropriate as a first choice in young and middle-age hypertensives, and in those with fast heart rate, but they should not be considered appropriate as the first-line therapy in the elderly with uncomplicated hypertension. Several years ago a plethora of publications showed that short-acting calcium antagonists may increase the risk for myocardial infarction and cancer. A few years ago two studies showed that calcium antagonists are less effective than angiotensin converting enzyme inhibitors in preventing cardiovascular events in diabetic hypertensive patients. However, recent results from large prospective randomized studies showed that calcium antagonists reduce cardiovascular morbidity and mortality in diabetic and non-diabetic hypertensive patients. Some investigators have suggested that angiotensin receptor blockers (ARBs) may increase the risk of myocardial infarction in hypertensive patients. However, recent meta analyses refuted this conclusions and showed that ARBs are probably as effective as other antihypertensive agents in prevention of myocardial infarction. Despite the concern that has been raised regarding the long-term safety of some antihypertensive agents, it is clear that lowering BP is safe and beneficial.     

A practical approach to achieving recommended blood pressure goals in diabetic patients.

Approximately 11 million Americans have both hypertension and diabetes mellitus. This double diagnosis places such patients at high risk for renal damage, especially end-stage renal disease. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends a blood pressure goal of less than 130/85 mm Hg to reduce or slow the onset of renal disease and cardiovascular events in patients with hypertension and diabetes mellitus. Recent data, however, now suggest that an even lower diastolic blood pressure goal (ie, <80 mm Hg) may be necessary. Studies have shown that use of angiotensin-converting enzyme inhibitors can prevent the progression of microalbuminuria to overt proteinuria, reduce proteinuria in patients with overt diabetic nephropathy, slow the deterioration of the glomerular filtration rate, delay progression to end-stage renal disease, and lower blood pressure. Thus, all diabetic patients with blood pressure greater than 130/80 mm Hg should begin angiotensin-converting enzyme inhibitor treatment and be titrated to moderate or high doses until the blood pressure goal is achieved. However, monotherapy still may not control blood pressure to the recommended target. Studies have shown that use of multiple antihypertensive agents is necessary and successful in helping patients reach their target blood pressure, and this may offer more renoprotection than one agent used singly. A case study that applies these concepts in outpatient practice is included.