Achieve Blood Pressure Levels Research Articles

Target blood pressure in diabetes patients with hypertension —What is the accumulated evidence in 2011?

There is overwhelming evidence that hypertension is an important risk factor for both macrovascular and microvascular complications in patients with diabetes, but the problem remains to identify appropriate goals for preventive therapies. A number of guidelines (the European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD) 2007, the Joint National Committee (JNC)-VII 2003, the American Diabetes Association (ADA) 2011) have for example advocated a blood pressure goal of less than 130/80 mmHg, but this suggestion has been challenged by findings in recent trials and meta-analyses (2011). The European Society of Hypertension (ESH) therefore recommends a systolic blood pressure goal of "well below" 140 mmHg. Based on evidence from both randomized controlled trials (hypertension optimal treatment (HOT), action in diabetes and vascular disease: preterax and diamicron MR controlled evaluation (ADVANCE), action to control cardiovascular risk in diabetes (ACCORD)) and observational studies (ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET), international verapamil-trandolapril study (INVEST), treat to new targets (TNT), and the National Diabetes Register (NDR)), it has been shown that the benefit for stroke reduction remains even at lower achieved blood pressure levels, but the risk of coronary events may be uninfluenced or even increased at lower systolic blood pressure levels. In a recent meta-analysis, it was therefore concluded that the new recommended goal should be 130-135 mmHg systolic blood pressure for most patients with type 2 diabetes. Other risk factors should also be controlled with a more ambitious strategy applied in the younger patients with shorter diabetes duration, but a more cautious approach in the elderly and frail patients with a number of vascular or non-vascular co-morbidities. In patients from East Asia, such as China, the stroke risk is relatively higher than the risk of coronary events. This must also be taken into consideration for individualized goal setting in relation to total risk, for example in patients from stroke-prone families. In conclusion, the current strategy is to have a more individualized approach to risk factor control in patients with type 2 diabetes, also relevant for blood pressure control.

Angiotensin receptor blockers for prevention of new-onset type 2 diabetes: A meta-analysis of 59,862 patients

BackgroundAngiotensin receptor blockers (ARBs) have been linked to reduced risk of new-onset diabetes, but the evidence was insufficient. Objective and methodsThe aim of this study was to evaluate the effect of ARBs on the development of new-onset type 2 diabetes. Randomized controlled trials (RCTs) about ARBs and new-onset diabetes were identified by electronic and manual searches. ResultsEleven RCTs with 79,773 patients (59,862 non-diabetic patients at baseline) were included in this study. Compared with control group, incidence of new-onset diabetes was significantly reduced in ARBs group [OR 0.79, (0.74, 0.84)] and various categories of ARBs subgroup. ARBs were associated with significant reduction in the risk of new-onset diabetes compared with placebo [OR 0.83, (0.78, 0.89)], beta-blocker [OR 0.73, (0.62, 0.87)], calcium channel blocker [OR 0.76, (0.68, 0.85)] and non-ARB [OR 0.57, (0.36, 0.91)]. ARBs were associated with significant reduction in the risk of new-onset diabetes in patients with hypertension [OR 0.74, (0.68, 0.81)], heart failure [OR 0.70, (0.50, 0.96)], impaired glucose tolerance [OR 0.85, (0.78, 0.92)] or cardiocerebrovascular diseases [OR 0.84, (0.72, 0.97)]. Compared with control group, incidence of new-onset diabetes was significantly reduced in ARBs group, irrespective of achieved blood pressure level. ARBs were associated with a lower incidence of new-onset diabetes in Western population [OR 0.81, (0.76, 0.85)] and Japanese population [OR 0.61, (0.48, 0.79)]. ConclusionThere is sufficient evidence that ARBs have beneficial effect in preventing new-onset type 2 diabetes. ARBs should be considered in patients with high risk of developing diabetes.

Hypertension Management

Elevated blood pressure is a major modifiable risk for cardiovascular disease (CVD) and the leading cause of preventable death worldwide. Current estimates indicate that ≈7.6 million premature deaths and 92 million disability-adjusted life years are attributable to suboptimal blood pressure.1 Most of the lifestyle causes of hypertension are well known, and clinical trials provide clear evidence that reducing blood pressure with antihypertensive drugs significantly decreases CVD morbidity and mortality. Despite this, the World Health Organization is predicting an epidemic of hypertension and, in clinical practice, most patients with hypertension are undiagnosed, untreated, or suboptimally treated.2 Against the backdrop of increasing CVD burden worldwide, the gap between what we know and do in hypertension prevention and management is a major cause for concern. Achieving optimum hypertension control to prevent hypertension-associated CVD has been a substantial challenge. There are multiple reasons for lack of blood pressure control, including health care system characteristics, as well as patient and physician characteristics.3 Treatment and control rates of hypertension are particularly low in most developing countries (typically <10%), and even developed countries have far from ideal levels …

Blood Pressure-Lowering Effects of Angiotensin Receptor Antagonist Monotherapy and in Combination with Other Anti-Hypertensive Drugs in Primary Care Settings in Japan

Combination therapy with multiple anti-hypertensives is required to achieve target blood pressure (BP) control and is recommended as the first-line therapy in hypertension. Although angiotensin receptor blockers (ARBs) may be combined with other anti-hypertensives, it is unclear how the effects of ARBs are influenced by co-administered anti-hypertensives. We investigated the effect of olmesartan medoxomil (OLM) when it is given alone (monotherapy) or concomitantly with other anti-hypertensives in 6507 OLM-naïve Japanese in “real world” clinical practice. After a 12-week treatment, BP was significantly reduced from baseline in both the monotherapy group and the combination therapy group (P < 0.0001). The BP-lowering efficacy after treatment and achievement rates of target BP were similar in both groups. In the combination therapy group, no significant difference of achieved BP level was detected between patients taking Calcium channel blockers and any other class of anti-hypertensive drugs. This study suggests that ARBs such as OLM-elicits BP-lowering efficacy as either a first- or second-line agent and its effects are minimally influenced by co-administered anti-hypertensives.

For the majority of patients with diabetes blood pressure and lipid management is not in line with recommendations. Results from a large population‐based cohort in Germany

To evaluate the management of cardiovascular risk factors in a population-based cohort of adults with diabetes mellitus in Germany. For the 9953 participants (50-74 years of age) of the ESTHER study, diabetes mellitus, hypertension, dyslipidemia and the respective medication were documented at baseline by their primary care physician. Blood pressure was taken and lipid levels were determined from a blood sample drawn at recruitment. Lifestyle factors (smoking, BMI, physical activity) were documented by the participants. Prevalence of pharmacotherapy for and control of hypertension and dyslipidemia among diabetic patients with these diagnoses were assessed and determinants were evaluated by multiple logistic regression. Diabetes mellitus was present in 1375 participants (14.2%). Almost 78% of diabetic participants had physician diagnosed hypertension, 86.0% received pharmacotherapy, but only 12.8% of those with anti-hypertensive medication achieved blood pressure levels below 130/85 mmHg. Obese participants were more likely to receive anti-hypertensive pharmacotherapy than non-obese ones: adjusted odds ratio (OR, 95% confidence interval (CI)): 3.58 (1.86-6.87). Gender had no influence on anti-hypertensive pharmacotherapy. Older diabetic patients with hypertension were less likely to have sufficient blood pressure control than younger ones. Dyslipidemia was documented in 50% of diabetic patients. Diabetic participants with coronary heart disease or hypertension were more likely to receive lipid-lowering pharmacotherapy than those without these conditions (adjusted OR 1.85 (95%CI 1.19-2.89) and 2.59 (95%CI 1.41-4.74), respectively). For most elderly with diabetes cardiovascular risk factor management continues to be not in line with recommendations.

Revival of nifedipine, a dihydropyridine-based calcium blocker

A recent analysis by the Blood Pressure Lowering Treatment Trialists' Collaboration revealed that any commonly-used blood pressure (BP)-lowering regimen reduced the risk of total major cardiovascular events, and larger reductions in BP produced larger reductions in the risk. These observations suggest that most of the differences among treatment regimens in their effects on cardiovascular outcomes could be explained by the differences in achieved BP level. However, it may also be true that some treatment regimen is superior or inferior to others with regard to the risk reduction of cardiovascular events. Indeed, the data from dihydropyridine-based calcium antagonist (DHP) trails are consistent in that they could not protect against new-onset heart failure or progression of renal disease in patients with left-ventricular systolic dysfunction or overt proteinuria, respectively. However, a multicenter, randomized, placebo-controlled, double-blind ACTION trial, which compared the effect of long-acting nifedipine or placebo on mortality and cardiovascular morbidity in patients with stable angina, revealed that nifedipine reduced the risk for new-onset overt heart failure by 29%. Further, an open-label, randomized prospective J-MIND trial, which compared the effect of long-acting nifedipine or enalapril, an angiotensin-converting enzyme inhibitor on onset and progression of nephropathy in hypertensive patients with type 2 diabetes, showed that long-acting nifedipine had an equipotent reoprotective effect on diabetic nephropathy. In this paper, we would like to propose our hypothesis that nifedipine may be unique and superior in its effects on heart failure and proteinuria compared with various DHPs. For ensuring our hypothesis, the following clinical issues would be addressed. Does nifedipine treatment alone decrease the progression of renal disease with overt proteinuria? If these answers are yes, are these beneficial effects of nifedipine superior to that of other DHPs with equihypotensive properties? Does nifedipine treatment also reduce oxidative stress markers? Are these unique effects of nifedipine correlated with its anti-oxidative properties? These prospective studies will provide further valuable information whether nifedipine may be a preferred DHP to achieve BP goals in hypertensive patients with systolic dysfunction or overt proteinuria.

Microalbuminuria In Primary Hypertension

Microalbuminuria, i.e., abnormal urinary excretion of albumin detectable by sensitive, low cost, and widely available tests, can be found in up to one third of non diabetic patients with primary hypertension. Microalbuminuria has been shown to predict an increased probability of suffering a cardiovascular event or death. The pathogenetic mechanisms leading to the development of microalbuminuria are not yet fully known: blood pressure load and increased systemic vascular permeability, possibly due to early endothelial damage, seem to play a major role. Increased urinary albumin excretion has been associated with several unfavorable metabolic and non metabolic risk factors and sub-clinical organ damage, such as left ventricular hypertrophy and carotid atherosclerosis. Microalbuminuria itself has recently been recognized as a sign of hypertensive target organ damage and since it reflects the influence of so many clinically relevant parameters, it can rightly be considered an integrated marker of cardiovascular risk, a unique feature among the several available prognostic predictors for stratifying risk in hypertensive patients. While microalbuminuria has proven to be a forerunner of overt renal damage in the presence of diabetes mellitus, conflicting clinical evidence makes this hypothesis tempting at the moment, but speculative in non diabetic hypertensives. Effective antihypertensive treatment, especially with drugs counteracting the renin angiotensin system, has been found to reduce urinary albumin excretion. More recently, regression from microalbuminuria to normoalbuminuria has been associated with an amelioration of cardiovascular outcome, regardless of achieved blood pressure levels and type of drug. This evidence emphasizes the usefulness of evaluating urinary albumin excretion not only to assess cardiovascular risk, but also to monitor the efficacy of treatment in clinical practice.

The role of combination antihypertensive therapy in the prevention and treatment of chronic kidney disease

The failure to achieve blood pressure (BP) control in the general population makes a substantial contribution to the development of chronic kidney disease (CKD) and subsequent renal failure. Each year, in the United States, more than 94,000 people develop end-stage renal disease; about 65% of these cases are directly attributable to hypertension and diabetes. Like hypertension, CKD does not produce symptoms for many years, and therefore its detection, prevention, and treatment are largely dependent on the vigilance of physicians and other health care providers. Current therapeutic advances make it possible to slow the progression of CKD and to improve clinical outcomes for these patients. Large, randomized, clinical hypertension trials have shown that tighter BP control, compared with less tight BP control, can reduce progression of renal disease by 30% to 50% and cardiovascular disease by 40% to 70%. Achieving BP levels of <130/80 mm Hg, as currently recommended for patients with diabetes or CKD, will often require three or more antihypertensive medications. Furthermore, reduction of BP should be accompanied by reductions in albuminuria and proteinuria to maximize potential benefits to the kidney. Evidence from numerous randomized controlled trials mandate that agents that block the renin-angiotensin system should always be included in the antihypertensive regimens of patients with CKD, particularly with the excellent safety data with serum creatinine levels <3 to 4 mg/dL. Fixed-dose combination agents are useful in bringing high-risk hypertensive patients to appropriate BP goals, primarily by simplifying the complex medical regimens in these patients.

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Commentary: Should BP targets be lower in diabetic patients with microalbuminuria or nephropathy?

The authors in the preceding paper have answered a number of specific questions regarding the management of diabetic renal disease. Using a systematic review, they have concluded that although urinary albumin excretion decreases in patients randomised to lower blood pressure (BP) levels within the normotensive range (&lt; 140/90 mmHg), no trials to-date have demonstrated a beneficial effect on glomerular filtration rate (GFR). Thus, the authors state that the available literature does not provide dat S a to support the assertion that BP-lowering within the normotensive range reduces the risk of renal replacement therapy. However, these findings require interpretation before they can influence clinical practice. The benefits of BP-lowering extend far beyond the glomerulus — a fact of crucial importance in terms of the macrovasculopathy so frequently seen inpatients with diabetic renal disease. Moreover, achieving BP levels within the normotensive range in these patients is in itself a success. The analysis provided by Kaiser et al. does suggest that, rather than lowering BP within the normotensive range, other therapeutic avenues may be more fruitfully explored to maximise health gain in this high-risk cohort.

Concluding remarks

The hypertension that occurs in association with obesity confers substantial cardiovascular risk and warrants an aggressive therapeutic approach. This should include lifestyle modifications that foster weight loss and enhance insulin sensitivity as a part of every therapeutic regimen. Although rarely sufficient in and of themselves, these lifestyle changes improve the response to antihypertensive medications and exert a beneficial effect on other aspects of the risk profile associated with obesity and hypertension. Combinations of antihypertensive drugs should be employed to achieve blood pressure levels in the range of those recommended for patients with type 2 diabetes. Agents that improve the metabolic profile (rather than those associated with deterioration of that profile) should be considered as part of the antihypertensive drug combination.

Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs.

Responsiveness to antihypertensive medications was investigated cross-sectionally in 559 individuals comprising all treated hypertensive patients identified within a representative sample (n = 3,532, aged 40-70 years) of the Jewish population in Israel. A rate of dosage score (a summed ranking of dosages of all drugs taken) of two or more increased significantly with increasing levels of body mass index (BMI) from 37.5% in levels less than 23, 54.9% in levels 23.0-29.9, and 76.4% in levels of 30 or greater (p less than 0.0001). Multivariate analyses, adjusting for age, gender, arm circumference, and ethnic group, confirmed the independent effect of BMI on dosage score (p less than 0.001). At each level of dosage score, mean blood pressure levels were equivalent at all levels of BMI after adjusting for potential confounders. This indicates that achieved blood pressure level and not BMI itself was the main determinant of the higher dosing regimens prescribed at higher levels of BMI. In representative subgroups, glucose tolerance (n = 372) and hyperinsulinemia (n = 190) were determined and were found to be positively associated with a dosage score of two or more (p less than 0.05) independently of BMI. These effects could not be accounted for by poor compliance or by altered drug absorption or disposition since overnight urinary drug excretion and plasma drug concentrations 2 hours after ingestion, measured in 80 randomly selected patients from the study group, were not different across BMI categories at similar dosages.(ABSTRACT TRUNCATED AT 250 WORDS)

The J-shaped relationship between coronary heart disease and achieved blood pressure level in treated hypertension: further analyses of 12 years of follow-up of treated hypertensives in the Primary Prevention Trial in Gothenburg, Sweden

The relationship between the blood pressure level achieved through antihypertensive treatment and the incidence of coronary heart disease (CHD) was studied in 686 middle-aged hypertensive men. The patients studied came from a random population sample and were followed-up for 12 years, yielding a total of 6563 patient-years for the study. Eighty-seven patients suffered a non-fatal myocardial infarction or died from CHD. The incidence of CHD showed a J-shaped distribution in relation to achieved treated systolic and diastolic blood pressure levels. The incidence of CHD, adjusted for entry characteristics, age, serum cholesterol, blood pressure and smoking habits, decreased with reductions in blood pressure achieved through treatment, to a level of about 150/85 mmHg, below which the incidence rate again increased. This J-shaped pattern was also observed when data from patients with pre-existing signs or symptoms of ischemic heart disease at entry were excluded. Using a quadratic term as the best fit to the observed relationship between achieved treated diastolic blood pressure level and the incidence of CHD, a Cox regression analysis showed that the nadir of the J-shaped incidence curve was at a diastolic blood pressure value of 81 mmHg. There did not seem to be any association between the absolute size of the blood pressure reduction during treatment and the incidence of CHD. Although we cannot exclude the possibility that the increased incidence of CHD in patients with a low treated blood pressure is due primarily to pre-existing but subclinical ischemic heart disease, our findings indicate that an excessive lowering of blood pressure in hypertensive patients may be harmful.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk Predictors in Treated Hypertension

The data for patients referred to the Dunedin Hypertension Clinic (975 men, 1,348 women) between 1953 and 1977 have been examined by the Cox proportional hazards method for significant age-corrected predictors of 8-year cardiovascular and total mortality. For men, some significant predictors were systolic and diastolic blood pressure (BP), indices of target organ damage (heart and eyes) and smoking at presentation, and achieved BP and serum cholesterol at follow-up. For women, serum cholesterol, diabetes, target organ damage (heart and eyes) and smoking at presentation, and achieved BP level at follow-up were predictors. Relative risk for total or cardiovascular mortality was increased in both sexes most by smoking and by increased levels of achieved BP.

Goals of antihypertensive therapy. Is there a point beyond which pressure reduction is dangerous?

It has been widely assumed that the preventive effect of antihypertensive treatment on cardiovascular events is increased as lower blood pressure (BP) is achieved. This assumption seemed logical in light of the well-known relationship between BP level and future cardiovascular events. Hypertension, however, develops over many years and is associated with both hypertrophic and atherosclerotic changes within the coronary and peripheral vessels. Antihypertensive drugs when instituted will bring down BP and often arterial blood flow within weeks. Coronary blood flow is limited to diastole. Theoretically then, very low diastolic BPs in coronary arteries with hypertrophic and/or atherosclerotic changes might precipitate a chain of events leading to a myocardial infarction and/or a lethal arrhythmia. Recently, results from several trials have been presented indicating a J-shaped relationship between achieved BP level and incidence of coronary heart disease. These trials are reviewed and problems in the interpretation of the findings such as biaz from varying risk at entry, varying follow-up time, and choice of statistical method, are discussed. Although, the burden of evidence strongly supports the hypothesis that low attained BPs are associated with an increased risk of a coronary heart disease event, problems in the interpretation of this evidence call for further analyses of the relationship within the large hypertension trials. Until such results are at hand caution should be to avoid decreasing BP below 85 mm Hg diastolic.

Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group

The Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities througout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115 + mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Controls of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100, P less than .01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100, P less than .01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with "mild" hypertension.

Five-Year Findings of the Hypertension Detection and Follow-up Program

The Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities throughout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115+mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Control of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100,<i>P</i>&lt;.01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100,<i>P</i>&lt;.01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with "mild" hypertension. (<i>JAMA</i>242:2562-2571, 1979)