Treatment for hypertension with diabetes mellitus

In the treatment for the hypertension patients with diabetes mellitus, the target blood pressure is below 130/80mmHg. As the first choice drugs, ARB, ACE inhibitor and Ca channel blocker are recommended. In the high normal blood pressure patient (130-139/80-89mmHg), the initial approach is life-style modification. In hypertension patients with diabetes (over 140/90mmHg), blood pressure should be controlled with the medication. The life-style modification should be performed even in the patients treated with anti-hypertensive drugs.     

Blood pressure control in eldery hypertension

Case of diabetes mellitus associated with essential hypertension are mostly type 2 diabetes mellitus(NIDDM) in elderly patients. In the JNC VI and JSH 2004, it is recommended that the therapeutic target blood pressure level should be lower then 130/80 mmHg in hypertension complicated with diabetes mellitus, and this target has recently obtained wide acceptance. On the other hand, the target blood pressure in elderly is recommended below 140/90 mmHg. Accordingly, diabetes mellitus in elderly hypertensives should be treated similarly as in the young and middle-aged. Because ACE inhibitors/ARBs or Ca blockers increase insulin sensitivity, these drugs should be used as the first choice in cases of elderly hypertensive patients complicated with diabetes mellitus.     

Definition and clinical characteristics of mild hypertension

Mild hypertension is defined as blood pressure level of 140-159 mmHg systolic and/or 90-99 mmHg diastolic. The patients with blood pressure level of mild hypertension occupy about 60% of total hypertensive patients in Japan, and most of them are free of subjective symptoms except elevated blood pressure. However, some of the patients with mild hypertension develop cardiovascular events, since thay have occasionally cardiovascular damages on this level of blood pressure and several risk factors of cardiovascular diseases such as diabetes mellitus and hyperlipidemia.     

Pharmacological prevention of atherothrombotic events in patients with peripheral arterial disease

Peripheral arterial disease (PAD) is strongly associated with atherosclerosis in the coronary and carotid arteries, leading to a highly increased incidence of myocardial infarction, ischaemic stroke and cardiovascular death. Fortunately, pharmacological interventions in large clinical trials have been as effective in subgroups of patients with PAD as in subjects with other atherosclerotic disease. Antiplatelet treatment is indicated in virtually all patients with PAD. Aspirin 75-325 mg day(-1) is considered as first-line treatment, and clopidogrel 75 mg day(-1) is an effective alternative. Statin therapy is indicated to achieve a target low-density lipoprotein cholesterol level of < or = 2.5 mmol L(-1) in patients with PAD and there is emerging evidence that even lower levels are beneficial. Lowering of plasma homocysteine by supplementing folic acid, vitamin B(12) and vitamin B(6) is not recommended in patients with mild to moderate hyperhomocysteinaemia in the 12-25 micromol L(-1) range, since it does not reduce the incidence of cardiovascular events. Antihypertensive treatment is indicated to achieve a goal blood pressure of < or = 140/90 mmHg or < or = 130/80 mmHg in the presence of diabetes or chronic kidney disease. All classes of antihypertensive drugs are acceptable for treatment of hypertension in patients with PAD, but angiotensin-converting enzyme inhibitors ramipril or perindopril are especially appropriate because they reduce the incidence of cardiovascular events beyond their blood pressure-lowering effects. Beta-blockers should not be used as first-line antihypertensive treatment. Diabetic patients with PAD should reduce their glycosylated haemoglobin to < or = 7%. In conclusion, pharmacological secondary prevention of cardiovascular morbidity and mortality in patients with PAD should be as comprehensive as that in patients with established coronary or cerebrovascular disease.     

Management of hypertension in CKD patients

The purpose of treatment for chronic kidney disease (CKD) is to preserve the renal function and to prevent the cardiovascular disease (CVD). CKD patients frequently present non-dipper and salt-sensitive type hypertension, which is a powerful predictor for both the CKD and CVD. Many previous clinical studies in CKD patients showed that appropriate blood pressure control was absolutely necessary to prevent the progression of CKD and development of CVD. From these studies, the target blood pressure for CKD patients is determined as less than 130/80 mmHg, if amount of urinary protein < 1 g/day, and 125/75 mmHg, if urinary protein > 1 g/day. Especially, blood pressure control using the RAS (renin-angiotensin system) inhibitor such as ARBs or ACEIs is superior to other classes of antihypertensive agents in reducing the amount of urinary protein and in preserving renal function. Thus, ARBs and/or ACEIs should be administered to CKD patients unless hyperkalemia or excessive increase in serum creatinine level is observed. Furthermore, hypertension in CKD patients is sometimes intractable and other classes of antihypertensive agents should be administered in addition to ARBs or ACEIs to obtain the target blood pressure.     

Fixed combination therapy of hypertension: focus on valsartan/hydrochlorothiazide combination (Diovan/HCT)

Hypertension is a major risk factor for cardiovascular morbidity and mortality. Monotherapy of hypertension is often ineffective, since it controls approximately 50% of the blood pressure of hypertensive patients. For lowering blood pressure to less than 140/90 mmHg (or <130/80 mmHg among people with diabetes or chronic renal disease) according to JNC-7 guidelines, combination therapy of two or more drugs is often necessary. The combination of a diuretic with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) is effective and provides the additional benefit of blocking the effects of angiotensin II, which is responsible for cardiovascular remodeling and its complications. ARBs may have an advantage over the ACEIs because they block the action of all angiotensin II directly, whereas ACEIs are ineffective in blocking angiotensin II generated by nonclassical ACE pathways. Valsartan (Diovan, Novartis) is one of the seven currently approved ARBs in the USA for the treatment of hypertension, and it has been shown to be very effective in controlling blood pressure given once-daily in doses of 80-160 or 320 mg. Its fixed combination with hydrochlorothiazide (HCT) is even more effective in controlling blood pressure in 70% of the cases. The most commonly used combinations are valsartan/HCT (Diovan/HCT), 80/12.5 and 160/12.5 mg given once-daily.     

Fixed combination therapy of hypertension: focus on valsartan/hydrochlorothiazide combination (Diovan®/HCT)

Hypertension is a major risk factor for cardiovascular morbidity and mortality. Monotherapy of hypertension is often ineffective, since it controls approximately 50% of the blood pressure of hypertensive patients. For lowering blood pressure to less than 140/90 mmHg (or <130/80 mmHg among people with diabetes or chronic renal disease) according to JNC-7 guidelines, combination therapy of two or more drugs is often necessary. The combination of a diuretic with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) is effective and provides the additional benefit of blocking the effects of angiotensin II, which is responsible for cardiovascular remodeling and its complications. ARBs may have an advantage over the ACEIs because they block the action of all angiotensin II directly, whereas ACEIs are ineffective in blocking angiotensin II generated by nonclassical ACE pathways. Valsartan (Diovan^®, Novartis) is one of the seven currently approved ARBs in the USA for the treatment of hypertension, and it has been shown to be very effective in controlling blood pressure given once-daily in doses of 80–160 or 320 mg. Its fixed combination with hydrochlorothiazide (HCT) is even more effective in controlling blood pressure in 70% of the cases. The most commonly used combinations are valsartan/HCT (Diovan/HCT), 80/12.5 and 160/12.5 mg given once-daily.     

Characterisitics of Japanese Guidelines for the Management of Hypertension 2009

Revised version of the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2009 (JSH2009) has been delivered in Jan. 2009 (Hypertens Res 32: 3-107, 2009). Followings are the main points of JSH2009 guidelines : (1) CV risk stratification and strategy of hypertension management are revised in consideration with of high-normal BP, metabolic syndrome(risk stratum-2), and CKD(risk stratum-3). (2) Tight control of BP levels < 130/85 mmHg is recommended in general hypertensive patients. More tight control is recommended in patients with DM, CKD, and post MI : BP < 130/80 mmHg. (3) Final target of BP in the elderly is < 140/90 mmHg. However BP should be reduced carefully by setting an intermediate target of < 150/90 mmHg in patients with 75 yrs or over. (4) BP control over 24 hours and usefulness of home BP measurement are stressed. Masked hypertension, morning surge, night-time hypertension, and sleep apnea syndrome are particularly important issues. (5) CCB, ARB, ACE inhibitor, diuretic, and beta-blocker are recommended as initial antihypertensive drugs, combination therapy such as ARB+diuretics or CCB are often necessary to achieve BP target. (6) Tight BP control and specific consideration for choice of drugs such as RA inhibitors are required in hypertension associated with organ damage and hypertension complicated with diabetes, CKD and metabolic syndrome.     

CB1-06: Benefits of Early Versus Later Hypertension Treatment and Control on Cardiovascular Outcomes in Those with Diabetes: Clinical and Research Implications

Background/Aims The benefits of early hypertension (HT) control in patients with diabetes (DM) may vary by degree of BP control achieved in the year after HT onset. Methods Retrospective cohort study, of 13,480 DM who met study criteria for new onset HT based on blood pressure (BP) measurements, ICD-9 HT diagnose, and pharmacy data. Multivariate logistic and proportional hazard regression models were used to model the impact of BP control in first year and baseline comorbidity on subsequent occurrence of stroke or acute myocardial infarction, with adjustment for demographic factors, comorbidities, and diabetes severity. Results During a mean of 37 months of follow-up time the rate of major CV events in those whose mean BP in the 12 months after HT onset was < 130/80 mm Hg, 130-139/80-89 mm Hg, and > 140/90 mm Hg was 4.9, 5.1, and 7.8 major CV events per 1000 person years respectively. CV events rates did not differ significantly for those above or below 130/80 mm Hg, but were significantly lower in those <140/90 mm Hg compared to those who >= 140/90 mm Hg at the end of the first year after HT onset (p=.0002). In multivariate models, BP control was a significant predictor of stroke, but not of myocardial infarction. Discussion Prompt control of HT within one year of onset significantly reduced likelihood of subsequent stroke. Benefits of BP control were not significantly modified by baseline comorbidities or severity of diabetes.     

CB1-04: Benefits of Early Versus Later Hypertension Treatment and Control on Cardiovascular Outcomes in Those with Diabetes: Clinical and Research Implications

Background/Aims The benefits of early hypertension (HT) control in patients with diabetes (DM) may vary by degree of BP control achieved in the year after HT onset. Methods Retrospective cohort study, of 13,480 DM who met study criteria for new onset HT based on blood pressure (BP) measurements, ICD-9 HT diagnose, and pharmacy data. Multivariate logistic and proportional hazard regression models were used to model the impact of BP control in first year and baseline comorbidity on subsequent occurrence of stroke or acute myocardial infarction, with adjustment for demographic factors, comorbidities, and diabetes severity. Results During a mean of 37 months of follow-up time the rate of major CV events in those whose mean BP in the 12 months after HT onset was < 130/80 mm Hg, 130-139/80-89 mm Hg, and > 140/90 mm Hg was 4.9, 5.1, and 7.8 major CV events per 1000 person years respectively. CV events rates did not differ significantly for those above or below 130/80 mm Hg, but were significantly lower in those <140/90 mm Hg compared to those who >= 140/90 mm Hg at the end of the first year after HT onset (p=.0002). In multivariate models, BP control was a significant predictor of stroke, but not of myocardial infarction. Discussion Prompt control of HT within one year of onset significantly reduced likelihood of subsequent stroke. Benefits of BP control were not significantly modified by baseline comorbidities or severity of diabetes.     

Management of hypertension in Japan--current state and clinical issue

The Japanese Guidelines for the Management of Hypertension (JSH2000) have been published in June, 2000, which basically followed the direction of 1999 WHO/ISH and JNC-VI guidelines. Target blood pressures for young or middle-aged hypertensive patients or hypertensives with diabetes are recommended to maintain less than 130/85 mmHg. In contrast, blood pressure control for hypertension in elderly is set taking the subject's age into consideration with systolic blood pressure lower than 140-160 mmHg and diastolic below 90 mmHg. Among hypertensive cardiovascular diseases, stroke is more common while ischemic heart disease is less common in Japanese than in Caucasians. Frequency of hypertension in Japan, which is estimated to be one-fourth of whole population and two-thirds of persons aged 60 years or over, has been declined in recent years, because of increasing treatment of hypertension, resulting in a decrease in stroke mortality and morbidity. However, the number of persons with hypertension controlled to below 140/90 mmHg seems to be about 20 percent of all hypertensives. Therefore, increases in rates of awareness, treatment and appropriate control of hypertension are the important issue for the management of hypertension in Japanese at present state.     

Blutdruck Zielwerte auf dem Pr��fstand

There is little evidence from controlled prospective studies to support the low blood pressure goals stipulated for the treatment of hypertension by present guidelines, especially in high-risk patients with diabetes, renal insufficiency or coronary heart disease. Aim of this review is to scrutinize the potential benefit and risk of low blood pressure on the basis of recent studies and secondary analyses of older studies. RESULTS: In patients with coronary heart disease or equivalent or with diabetes lowering systolic blood pressure to 130 to 135 mmHg reduced primary or secondary cardiovascular endpoints in the majority of studies. Between 120 and 129 mmHg some positive effects could be shown in patients with coronary heart disease but not in patients with diabetes or metabolic syndrome. In patients with diabetic or nondiabetic nephropathy including those with proteinurea no convincing data exist which show a better outcome with systolic blood pressure below 130 versus below 140 mmHg. However, several studies suggest that the risk of stroke may decrease by lowering systolic pressure to 120 mmHg or even lower. Below 120 mmHg an increased risk of cardiac and noncardiac events or death was shown in quite a number of studies. In patients between 70 and 80 years, current evidence suggests lowering systolic blood pressure to 135 to 145 mmHg and in those above 80 years to 145 to 155 mmHg. No evidence was found to justify different diastolic pressure goals for different groups of patients; optimal values fall between 70 and 85 mmHg. Limitations of recent studies are short follow-up, few event rates and small differences in achieved pressure between groups leaving uncertainty about long-term effects. PRACTICAL CONSEQUENCES: Apart from prevention of stroke there is sparse evidence that lowering systolic blood pressure below 130 mmHg may be beneficial. Current evidence suggests that lowering systolic and diastolic pressure into a range of 130 to 140/70 to 85 may be adequate for all patients with the exception of children, adolescents and patients over 80 years. Further lowering of systolic pressure seems to offer little additional benefit and lowering diastolic pressure below 70 mmHg might increase risk.     

Status of mild hypertension guidelines in Japan and abroad

Historically patients with systolic blood pressure level 140 to 159 mmHg or diastolic blood pressure level 90 to 99 mmHg had been defined as mild hypertension. However, the word of mild hypertension is not used in recent guidelines, such as JNC 7 and ESH/ESC 2007, although it is still used in JSH2004 and BHS IV. Patients with mild hypertension in JSH2004 are diagnosed as high risk hypertension if these patients are complicated cardiovascular organ damage, cardiovascular disease, or diabetes mellitus etc. Personally, I think the word of mild hypertension should be changed to another word or applied to patients with low risk hypertension.     

Diabetes mellitus and hypertension: a mandate for intense treatment according to new guidelines

Diabetics without a prior myocardial infarction have the same risk of a future myocardial infarction as nondiabetics with a prior myocardial infarction; however, epidemiologic studies suggest that lower blood pressure treatment goals may have potential benefit for diabetics with hypertension. Low-dose diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and dihydropyridine calcium antagonists have reduced cardiovascular events in patients with diabetes. Angiotensin receptor blockers with diabetic renal disease have reduced the rate of end-stage renal disease, whereas dihydropyridine calcium antagonists show no benefit. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers reduce overall mortality, cardiovascular events, and the development of the overt nephropathy in high-risk patients with diabetes without advanced renal disease. The blood pressure treatment goal for patients with diabetes without macroalbuminuria is less than 130/80 mm Hg and less than 125/75 mm Hg for patients with diabetes and nephrotic syndrome. To achieve these goals, multiple antihypertensive drugs are required.     

Hypertension associated with stroke

Antihypertensive treatment for hypertensive patients with stroke differs according to clinical subtypes (hemorrhage or ischemia) and phases (acute phase or chronic phase). In cerebral infarction that is not an indication for thrombolytic therapy, antihypertensive therapy is indicated when systolic pressure is > 220 mmHg or diastolic pressure is > 120 mmHg. In cerebral hemorrhage, a systolic blood pressure > 180 mmHg or a mean blood pressure > 130 mmHg is an indication for antihypertensive therapy. In the chronic phase of stroke, the eventual target of blood pressure control should be < 140/90 mmHg. Antihypertensive drugs recommened in the chronic phase are Ca channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, etc. In patients with diabetes mellitus or atrial fibrillation, ACE inhibitors and ARBs are recommended.     

Guidelines for the treatment of hypertension in diabetics

Patients with diabetes mellitus are often associated with hypertension. Hypertension increases the incidence of cardiovascular disease and accelerates the progression of diabetic nephropathy. Japanese Society of Hypertension made own guidelines for the management of hypertension(JSH2000) in 2000. Diabetics are stratified into the high risk group irrespective of their blood pressure levels. Target blood pressure is less than 130/85 mmHg. Hypotensive agents will be initiated at more than 140/90 mmHg along with glycemic control and lifestyle modification. When their blood pressure is within the high normal(130-139/85-89 mmHg), lifestyle modification as well as glycemic control will be initiated. If their blood pressure is not lowered to less than 130/85 mmHg during the next 3-6 months, hypotensive agents will be started. ACEIs, Ca-antagonists and alpha-blockers will be the first line hypotensive agents, since these hypotensive agents improve organ damages and insulin sensitivity and do not worsen lipid metabolisms. Recent guideline made by Japan Diabetes Society in 2003 lowered the target blood pressure furthermore to less than 130/80 mmHg and added angiotensin receptor blockers as one of the firstline hypotensive agents.     

Treatment After Myocardial Infarction

Persons after myocardial infarction (MI) should have their modifiable coronary artery risk factors intensively treated. Hypertension should be treated with beta blockers and angiotensin-converting enzyme (ACE) inhibitors. The blood pressure should be reduced to <140/90 mmHg and to <130/80 mmHg in persons with diabetes or renal insufficiency. The serum low-density lipoprotein cholesterol should be reduced to <70 mg/dl with statins if necessary. Diabetics should have their hemoglobin A_1c reduced to <7.0%. Aspirin or clopidogrel, beta blockers, and ACE inhibitors should be given indefinitely unless contraindications exist to the use of these drugs. Long-acting nitrates are effective antianginal and antiischemic drugs. Postinfarction patients at very high risk for sudden cardiac death should have an implantable cardioverter-defibrillator. The two indications for coronary revascularization are prolongation of life and relief of unacceptable symptoms despite optimal medical management. Dr. Aronow has no real or apparent conflicts of interest relating to the subject under discussion.     

Management of hypertension with diabetes mellitus in the elderly

The number of an elderly patient who has hypertension with diabetes mellitus has been increasing year by year since the life style of people has become Americanized in our country. Metabolic syndrome is characterized by hypertension, dyslipidemia, central adiposity and insulin resistance. It is recently recognized as the high risk for the macrovascular disease such as cerebral infarction and acute myocardial infarction. In diabetic patients, to prevent the life-threatening event or slow complications intensive blood pressure control is as efficacious as good glycemic control. The optimal blood pressure level to reduce hypertension-related morbidity and mortality in diabetic elderly has been proposed 130/80 mmHg in JSH 2004. The blood pressure level in the elderly should be lowered very slowly with careful monitoring of systemic ischemia. Early use of antihypertensive drug combinations is gaining favor. As the first step therapy would be recommended angiotensin receptor blocker, angiotensin-converting enzyme inhibitor and sustained release calcium channel blocker. Especially in the elderly, good control of life-style related diseases would be achieved through a team effort comprising the clinician, psychologist, nurse, pharmacologist, dietitian, other professionals and the patient's family. Comprehensive geriatric assessment can facilitate the maintenance of drug compliance for well control of blood pressure level.     

Treatment of hypertension in diabetes: what is the best therapeutic option?

Patients with diabetes mellitus have a high risk of cardiovascular disease, and the latter is the leading cause of premature mortality in diabetic patients. Treatment of risk factors and comorbidities, such as hypertension, is very important and may effectively prevent cardiovascular events. The blood pressure goal in diabetic patients should be below 140/90 mmHg, probably down to 130–135/85 mmHg, although the evidence for this is scarce. To reach this blood pressure goal, intensive lifestyle intervention and often combinations of different antihypertensive drugs must be initiated. In combination treatment, a blocker of the renin–angiotensin system should be included, and according to the results of the ACCOMPLISH trial, a combination of a renin–angiotensin system blocker and a calcium channel blocker should probably be the first choice.     

Treatment of hypertension in diabetes: what is the best therapeutic option?

Patients with diabetes mellitus have a high risk of cardiovascular disease, and the latter is the leading cause of premature mortality in diabetic patients. Treatment of risk factors and comorbidities, such as hypertension, is very important and may effectively prevent cardiovascular events. The blood pressure goal in diabetic patients should be below 140/90 mmHg, probably down to 130-135/85 mmHg, although the evidence for this is scarce. To reach this blood pressure goal, intensive lifestyle intervention and often combinations of different antihypertensive drugs must be initiated. In combination treatment, a blocker of the renin-angiotensin system should be included, and according to the results of the ACCOMPLISH trial, a combination of a renin-angiotensin system blocker and a calcium channel blocker should probably be the first choice.