I brazilian position statement on arterial hypertension and diabetes mellitus

SPECIAL ARTICLE

Mailing Address

Keywords: Hypertension; Diabetes Mellitus; Obesity; Adults; Overweight; Cardiovascular Risk.

Concept and Epidemiology

Arterial hypertension (AH) is defined when blood pressure (BP) levels are >140 mmHg and/or 90 mmHg for systolic and diastolic BP, respectively, in at least two separate measurements, in the presence or absence of diabetes mellitus (DM)¹.

The diagnosis of DM is confirmed by the finding of fasting plasma glucose > 126 mg/dL in two measurements, and/or blood glucose > 200 mg / dL after overloading with 75g of dextrose, and / or random glucose measurement > 200 mg/dL in the presence of unmistakable symptoms of diabetes, and/or, more recently, glycated hemoglobin > 6.5% in two samples, by the HPLC method².

AH and DM represent major public health problems and often coexist in clinical practice. At present, there is a trend to increase in the prevalence of AH and DM, possibly related to the growth of the elderly population, as well as overweight and obesity rates³.

According to the International Diabetes Federation, there were 285 million diabetic individuals in 2010 worldwide and it is estimated that there will be 438 million in 2030, with 90% of cases of type 2 DM. The impact of this situation in developing countries is immense⁴.

The association between AH and DM was first described in the 70s, observed in both sexes and at any age range. The prevalence of hypertension is two to three-fold higher in diabetics than in the general population⁵, and about 70% of diabetics are hypertensive^3,6. A meta-analysis of 102 prospective studies and 698,782 individuals showed that the presence of DM increases by two-fold the risk of coronary artery disease (CAD), cerebrovascular accident (CVA) and CV death. According to this meta-analysis, 10% of CV deaths in developed countries can be attributed to the presence of DM⁷.

The coexistence of the two conditions substantially increases the risk of acute myocardial infarction (AMI), CVA and mortality from all causes, as well as the risk of heart failure (HF), kidney disease (KD) and microvascular complications⁸.

Origin of Hypertension in DM

Chronic hyperglycemia and hence, the associated insulin resistance can lead to AH through several physiopathological mechanisms that are not fully understood. In vitro observations show that insulin can directly stimulate the activity of sodium potassium adenosine-triphosphatase and several ionic channels and pumps, increasing the intracellular ion concentration, with the increase in intracellular calcium being an important determinant of vasoconstriction. It is also known that high levels of leptin cause increased activity of the sympathetic nervous system, which leads to increased cardiac output and peripheral vascular resistance. Excess insulin is also is also able to reduce natriuresis by direct renal tubular mechanism, leading to an accumulation of salt and water. Salt-resistant AH is common in these patients^9,10.

The current and most relevant factor described as a cause of AH in diabetics has been oxidative stress, resulting from hyperactivity of metalloproteinases in patients with metabolic syndrome and DM. This leads to a reduction in the production and activity of protective vasodilator substances such as nitric oxide. Hydrogen peroxides, which are substrates and cofactors of the metabolism of these metalloproteins create, in the subendothelial microenvironment, the activation of potent vasoconstrictors through the local activation of the renin-angiotensin-aldosterone system (RAAS), and finally, increase in local concentration of angiotensin II¹¹.

All these mechanisms acting in an integrated manner, in a hostile environment of higher risk, are adjuvants not only for the genesis of hypertension, but also for the development of CVD, due to the process of initial endothelial dysfunction to the genesis of atheromatous plaques.

Cardiovascular Risk Stratification

Since 1980, evidence has shown that the presence of DM confers increased risk of CV death, both in men and women¹⁰. These studies have shown that either isolated or associated with other CV diseases such as hypertension and dyslipidemia, DM is closely related to the increased incidence of atherosclerosis¹¹.

Outcome studies carried out in the last decade also found in the association between AH and DM, a significantly increased incidence of fatal and nonfatal CV events, which led to the implementation of specific conducts over time to minimize the risk in this group of patients¹².

In this context, in diabetic subjects, even with BP considered normal, there is a moderate increase in CV risk, and in the presence of established AH, the risk will be high or very high (Table 1)¹.

Clinical and Laboratory Assessment

The clinical and laboratory assessment follows the same set of investigations performed in hypertensive patients without DM, plus some additional points¹.

The clinical history is important to verify the time of disease evolution, the search for other associated CV risk factors, the investigation of drugs that can further raise BP, presence of lifestyle habits that can aggravate the clinical presentation, detection of target-organ lesions and the possible presence of established CV disease. Similarly, the physical examination must be thorough and careful, also in search of evidence of secondary hypertension, target-organ lesions and possible signs of cardiovascular disease¹³.

BP must be systematically measured in the supine and standing positions due to the possibility of higher incidence of postural hypotension. The measurement of waist circumference (WC) for the evaluation of visceral obesity adds further information to the initial investigation (normal values < 88 cm for women and < 102 cm for men). The dilated fundus examination (DFE) has special indication, as it will be useful to detect changes related to DM, as well as those related to hypertension itself¹⁴.

Laboratory evaluation initially recommended for all hypertensive individuals should be maintained, including: urinalysis; measurement of serum potassium, serum creatinine, fasting glucose, lipid profile, uric acid and electrocardiogram.

In addition to these tests, it is important to perform: a) echocardiography for better assessment of ventricular function and mass b) exercise test to evaluate functional capacity and possible presence of subclinical ischemic alterations c) microalbuminuria may be initially performed by measuring in duplicate the albumin/creatinine ratio in an isolated urine sample. If available, carotid ultrasound should be performed, which may indicate the presence of incipient intima-media thickening of the carotid artery (> 0.9 mm) or presence of atheromatous plaque^15,16.

Additional tests aimed to every organ or system may be indicated depending on the finding of specific alterations.

Diabetes monitoring tests should obviously be routinely performed. In addition to fasting glucose, assessment of postprandial glucose and measurement of glycated hemoglobin (HbA1C) are indicated for this purpose¹⁷.

Kidney Alterations

AH and DM account for more than 50% of the causes of Chronic Kidney Disease (CKD). The kidneys are the target organ that undergoes specific systemic processes entailed in DM and AH. Approximately 5% to 20% of the patients with DM may have albuminuria at the time of diagnosis.

In the early stages, the vascular lesions are usually discrete, but with disease evolution, the lesions become more severe. Approximately 30% to 50% of patients with DM have a parallelism between clinical manifestation and pathological kidney alterations¹⁸.

Among the mechanisms involved is glomerular hyperfiltration, which can cause extracellular matrix accumulation through pathways that increase TGF-β expression. Glomerular hyperfiltration is capable of stimulating the RAAS, protein kinase C, in addition of TGF-β. These facts explain why drugs that block the RAAS have additional beneficial effects in addition to the antihypertensive one¹⁹.

Before the age of effective anti-hypertensive drugs, proteinuria occurred in 40% of patients and more than 18% progressed to end-stage CKD. Albuminuria was present in 15% to 30% of cases, few patients developed proteinuria of around 500 mg / day and some developed nephrotic levels. Serum creatinine elevation occurs in 10% to 20% of patients and the risk is higher in African-Americans, the elderly and patients with predominant systolic hypertension (> 160 mmHg). In 2% to 5% of patients, progression to renal failure occurred in the following 10 to 15 years²⁰.

Brain Alterations

Brain disease is the leading cause of morbidity in diabetic patients, and cerebrovascular accident (CVA) is responsible for 20% of deaths in diabetics²¹. There is a direct association between BP and mortality from CVA in diabetics and non-diabetics. This association increases with advancing age²². A large observational study showed a two-fold higher chance of CVA during 19 years of follow-up in those with the combination of diabetes and hypertension compared to hypertensive individuals only²³.

Diabetics have an increased risk of dementia, including Alzheimer's disease. Even diabetics without dementia have worse performance in cognitive tests, when compared with individuals without DM²⁴. In turn, hypertensive diabetics have an increased likelihood of cognitive deficits than normotensive ones²⁵. The early identification and treatment of these individuals may have an impact on quality of life, but also on better adherence to prescribed treatments.

Peripheral Artery Disease

Peripheral Arterial Disease (PAD) can affect different vascular territories. In DM, PAD is more often distal, femoropopliteal and tibial, whereas in AH, smoking, and hypercholesterolemia, vascular involvement is mainly proximal, aortoiliac and femoral²⁶. Approximately 65% of patients with some form of dysglycemia have PAD²⁷. In Brazil, 12% to 20% of patients with lower-limb (LL) PAD have DM and the risk of diabetic men developing PAD is 6.6 times higher than non-diabetic ones²⁸.

The main causes of PAD identified in the U.S. registry REACH (Reduction of Atherothrombosis for Continued Health) were DM and AH in Hispanics and African-Americans, while hypercholesterolemia was the main cause in Caucasians. The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) study showed that the duration of DM and the presence of micro/macroalbuminuria are important predictors of PAD severity and left ventricular failure in patients with coronary artery disease (CAD)²⁹. The PAMISCA study found 42.6% of PAD in hypertensive patients with acute coronary syndrome. The mortality among those with PAD was higher (2.3% versus 0.2%, p < 0.01)³⁰. Left ventricular hypertrophy affects up to 50% of patients with PAD, giving them a worse prognosis³¹.

Lower-limb PAD assessment includes: (a) Ankle Brachial Index (ABI - important in diabetic patients in the asymptomatic phase of PAD, to identify individuals at high risk of amputation), (b) treadmill exercise test (especially useful in diabetics with atypical LL symptoms or normal ABI and claudication symptoms), (c) lower-limb arterial duplex scan (locates and quantifies arterial lesions, in addition to analyzing the patency of grafts or stents), (d) magnetic resonance angiography (e) CT angiography, (f) coronary angiography (evaluation for revascularization)^32,33.

Heart Disease

Hypertensive patients have a higher risk of developing cardiac abnormalities; however, in association with DM, these alterations are more intense and have an early onset³⁴.

Studies have shown that alterations in myocardial cells, capillaries and interstitium, which lead to systolic and/or diastolic dysfunction, are much more pronounced in diabetic patients with a history of hypertension³⁵ and both diabetes and insulin resistance lead to alterations in the structural and molecular mechanisms. The incapacity of the myocardium to metabolize pyruvate results in lipid accumulation in the heart muscle and decrease in glucose uptake by myocytes³⁶.

Hyperinsulinemia is also associated with increased levels of free fatty acids and increased sympathetic activity, which are factors that lead to cardiac hypertrophy and the accumulation of intracellular triglycerides³⁷. However, these physiopathological chains are markedly exacerbated when BP levels are high, triggering other parallel mechanisms that induce hypertrophy, fibrosis and apoptosis. Oxidative stress has a strong participation, promoting the abnormal gene expression and signal transduction alterations, leading to myocyte death³⁸.

Other disorders also participate in myocardial injury; among them, autonomic neuropathy and mitochondrial dysfunction, common in DM, are adjuvant factors in reducing energy formation for adequate heart performance³⁹. These aspects of cardiac injury are the initial pathways for the full development of cardiomyopathy, with all the characteristics of heart failure⁴⁰.

Blood pressure, blood glucose and lipid goals

Blood pressure goals recommended by the VI Brazilian Guidelines on Hypertension¹ is 130/80 mmHg, regardless of the presence of micro- or macrovascular complications. More stringent BP reductions have shown no benefit in this population and are not recommended⁴¹.

Glycemic goals recommended by several scientific societies^3,6 include control of fasting blood glucose, postprandial blood glucose and HbA1C^2,42. Different societies differ in relation to these values and suggest an individualized goal according to age, comorbidities, life expectancy and glycemia variability^2,42. The Guidelines of the Brazilian Diabetes Society⁶ recommend the following:

More stringent HbA1c goals (6% to 6.5%) may be recommended in special groups: short disease duration, long life expectancy and in the absence of CV disease, as long as it is safe for the patient and there is no risk of hypoglycemia, as the importance of metabolic memory and glycemic variability in disease complications has been recently recognized. On the other hand, less stringent HbA1c goals (7.5% to 8%) are tolerated in elderly patients with frequent hypoglycemic episodes, short life expectancy, and significant cardiovascular complications and in patients with difficulty to achieve the goal even after effective use of multiple agents, including insulin^12,42.

The lipid levels goals in the diabetic population also differ according to the recommendations by different scientific societies (Table 2).

Individual CV risk must be assessed in hypertensive patients and the recommendations should be similar to those given to the general population regarding lipid goals. However, the European Guidelines⁴³ consider that the most significant classic risk factors, among which is severe hypertension, constitute a high or very high risk for CV death, deserving an appropriate LDL-C goal (<100 mg/dL), even in primary prevention of CVD and without DM.

Nondrug treatment of DM and AH

The non-drug treatment of AH in diabetics basically consists of decrease in body weight, low-sodium diet, regular exercise, a diet rich in fruits and vegetables (DASH diet), smoking and alcohol consumption cessation and treatment of obstructive sleep apnea. Weight reduction is recommended for all age groups⁴⁶. The reduction of abdominal circumference with weight reduction is associated with improved BP control and some metabolic parameters, such as lipids and glycemia⁴⁷. Some appetite suppressants may induce blood pressure increase, and can therefore be used with caution. In patients with severe obesity, bariatric surgery reduces mortality and decreases blood pressure and is associated with better control of diabetes⁴⁸.

The effectiveness of decreasing salt intake in the specific diabetic population is not known, and the indications in this population are based on studies including hypertensive diabetics and non-diabetics.

A diet low in sodium promotes rapid and significant decrease in BP in patients with resistant hypertension⁴⁹. In spite of individual differences in sensitivity, even modest reductions in the amount of salt are generally effective in reducing BP. The daily requirement for sodium in humans is contained in 5 g of sodium chloride or table salt. The average intake of Brazilians corresponds to twice the recommended amount⁴⁹.

Patients who regularly consume high doses of alcohol should be encouraged to attain total withdrawal from alcohol consumption, as it interferes not only with BP control, but especially with glucose level control.

Aerobic exercises (isotonic) together with resistance exercises lower blood pressure and are indicated not only for the treatment, but also for prevention of hypertension⁵⁰. The recommended amount of exercise is at least five times a week, 30 minutes of moderate continuous or accumulated physical activity.

The use of continuous positive airway pressure (CPAP) is the treatment of choice for patients with severe apnea/obstructive sleep apnea hypopnea syndrome (OSAHS). This procedure improves the episodes of apnea / hypopnea and helps in the correction of metabolic disorders (glucose). There is evidence that the use of this device can help to control blood pressure, in blood pressure drop during sleep, to improve quality of life and to reduce clinically relevant cardiovascular outcomes⁵¹. Alcohol intake worsens apnea/hypopnea episodes.

Drug Treatment of Dyslipidemia

In diabetics, the most commonly found dyslipidemias are hypertriglyceridemia, low HDL-C and increased small, dense LDL particles. The absolute levels of LDL-C, however, are similar in diabetic patients and the general population⁴⁵. There are no peculiarities regarding the type of dyslipidemia found in hypertensive patients. Although frequently there are no elevated levels of LDL-C, the treatment is indicated to achieve goals related to high risk of CV events for hypertensive patients with DM.

Statins should be the drug of choice for treatment of hypercholesterolemia, while fibrates must be chosen in cases of severe hypertriglyceridemia. Other drugs available are niacin and omega-3 fatty acids for the adjuvant treatment of hypertriglyceridemia and bile acid sequestrants and ezetimibe for the treatment of hypercholesterolemia.

Meta-analysis of statin studies showed that for every reduction of 39 mg/dL of LDL-C observed, there was a 12% reduction in total mortality and 19% in CV mortality⁵². The risk of coronary events was also reduced by 23% and the risk of CVA by 17%². A higher reduction of LDL-C reduces major cardiovascular events by 50%⁵³. A meta-analysis evaluating the treatment of dyslipidemia with statins in diabetic patients showed a reduction of cardiovascular mortality as well as cardiovascular outcomes, similarly to the non-diabetic population⁵⁴.

Thus, statins have been shown to be effective drugs for the treatment of hypertension or dyslipidemia in diabetic patients, despite recent warning from the FDA⁵⁵ regarding its prescription, due to the increased risk of diabetes. The low incidence of diabetes was largely confined to patients with previous dysglycemia, as pre-diabetics and glycemic changes were mild, even among diabetic patients. Regarding fibrates, a meta-analysis published in 2010⁵⁶ showed reduced risk of overall cardiovascular events by 10% and coronary events by 13%, but there are no specific meta-analysis data on the use of fibrates in an exclusively diabetic or hypertensive population.

The ACCORD Lipid study⁴¹involved diabetics who received treatment with placebo or simvastatin associated with fenofibrate. In this study, there was no reduction in cardiovascular outcomes with the combination of fenofibrate and simvastatin. However, subgroup analysis of this study showed that individuals with triglyceride levels > 204 mg/dL concomitant with HDL-C levels < 34 mg / dL had benefited from using fenofibrate. Another large study involving diabetics was the FIELD study⁵⁷, which showed a 24% reduction in nonfatal AMI, 21% in coronary revascularization and 11% in overall cardiovascular events. None of these studies, however, demonstrated a reduction in mortality. There have been, to date, no studies that evaluated fibrates in an exclusively hypertensive population, but they are considered safe drugs when indicated for the treatment of dyslipidemia⁵⁸.

The therapeutic goals, as recommended in the guidelines^42,59, are different for diabetics. Table 3 shows the indications for statin use in diabetic patients.

Drug Treatment of DM in the Hypertensive Patient

The algorithm for the treatment of diabetes is updated annually by the American Diabetes Association (ADA)⁵⁹ and, according to the final positioning, metformin is recommended as the drug of choice as long as it is well tolerated and in the absence of contraindications⁶⁰. If an effective glycemic control has not achieved within three months, the combination of other drugs is necessary. The choice of the second drug should take into account the patient's age, life expectancy, complications of DM, significant comorbidities, time of disease, need for weight control, risk of hypoglycemia and available resources, with cost being a true limiting factor.

A combination of drugs can be prescribed as early as at the diagnosis when higher blood glucose levels are present⁶¹. As second choice therapy, there are drugs such as thiazolidinedione, represented by pioglitazone, DPP-4 (dipeptidyl peptidase-4) inhibitors, GLP-1 (glucagon-like peptide-1) agonists, sulfonylureas, as well as insulin⁶². Glinides and alpha glucosidase inhibitors, represented by Acarbose, also represent less validated options for treatment of DM. If good glycemic control is not achieved within three months, other drugs and/or basal insulin should be associated to allow better and faster glycemic control and if this does not occur in three months, the option for multiple-dose insulin therapy may be necessary. According the 2012 position statement of the ADA/EASD, the choice of therapy should be individualized⁶³.

The change in lifestyle is capable of decreasing HbA1c levels similar to the use of metformin and sulfonylurea, of 1% to 2%. Monotherapy is not always sufficient to control the hyperglycemia, and as in the treatment of AH, the association of different drugs is required to achieve adequate control of blood glucose and glycated hemoglobin (Figure 1)¹².

Drug Treatment of AH in the DM Patient

In patients with diabetes and hypertension, the main determinant of cardiovascular benefits of antihypertensive medications is achieving the BP goal with treatment⁶⁴. Although the role of blood pressure control is unquestionable, a growing number of studies suggest that some drug combinations have advantages in protecting the kidneys, blood vessels and heart, as well as the BP control itself⁶⁴.

In diabetic patients with BP between 130-139 mmHg and 80-89 mmHg, the ADA recommends changes in lifestyle for a maximum of three months. These are key elements in reducing blood glucose and for proper control of pressure, especially after weight loss in obese patients, and they should be recommended for all diabetic hypertensive patients. If during this period there is no adequate pressure reduction, drug treatment should be started².

If the BP levels are > 140/90 mmHg, in addition to changes in lifestyle, drug treatment should be started immediately^1,59. In these conditions it is suggested that the BP goal is 130/80 mmHg, reinforced by the results of the ACCORD trial⁵⁹. For this goal to be achieved, it is almost always necessary to start antihypertensive treatment with two or more drugs of different classes. The presence of kidney disease should be stratified to define the best approach^1,59.

Several studies have demonstrated the benefits of Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) in hypertensive diabetic patients with microalbuminuria (30-300 mg/24 h)⁶⁵. These classes are the first choice for the initial treatment of hypertensive diabetic patients with renal disorders.

In diabetic patients with no established nephropathy, studies as the ALLHAT⁶⁶ indicated that other classes of antihypertensive drugs in addition to ACE inhibitors, such as diuretics and calcium channel antagonists (CCA) have similar protective effect in patients with hypertension and diabetes and can be used as first choice for treating this group of patients. ARBs may be used in patients who cannot tolerate ACE inhibitors¹.

The VI Brazilian Guidelines on Hypertension¹ recommend that in diabetic patients without nephropathy, all antihypertensive agents can be used; however, the combination of renin-angiotensin system blockers with CCA may be beneficial⁶⁴.

Table 4 summarizes the essential considerations for the use of the major classes of antihypertensive drugs in diabetic patients.

Table 5 shows the main guidelines for the treatment of hypertensive patients with diabetes.

Oral Antidiabetic agents and Cardiovascular Risk

The cardiovascular safety of thiazolidinedione (TZD) has been questioned⁷³ and rosiglitazone, alone or combined, showed an association with myocardial infarction without statistical significance when compared with metformin⁷⁴. The risk profile of pioglitazone seems more favorable, possibly by decreasing the atherosclerotic plaque inflammation, increasing HDL-c and decreasing high-sensitivity C-reactive protein⁷⁵. The ADA/EASD document⁷⁶ states that metformin is a useful drug in the presence of CAD, and pioglitazone use results in a modest reduction of major cardiovascular events and alerts for the increased risk of heart failure induced by TZD in the elderly older than 80 years ⁸⁰. Table 6 shows the major drugs, their advantages and disadvantages.

Peculiar Aspects of Vascular Intervention

There are certain peculiarities in patients with AH and DM, especially if the BP levels are elevated at the time of the intervention leading to increased vascular and non-vascular complications.

In diabetics, coronary artery disease manifests as the most severe form, with higher frequency of multivessel disease, more severe and diffuse obstructions, smaller caliber arteries, higher prevalence of total occlusions and trunk lesions and greater thrombogenic potential. For these reasons, although the indication for clinical treatment, surgical or percutaneous revascularization is not substantially different between diabetics and non-diabetics, the results are worse for percutaneous revascularization in diabetic patients, especially in insulin-dependent and / or those with poor metabolic control.

While the percutaneous treatment of patients with single-vessel or low anatomical complexity disease is clearly established in practice and substantiated by studies that showed similarity of results in comparison with the surgical outcome, patients with multivessel disease, complex anatomy and basic clinical risk still have CABG as the primary recommendation according to the Syntax⁷⁷and ARTS II⁷⁸ studies.

The angiographic success rate of elective percutaneous procedures is similar between diabetic and nondiabetic patients. However, diabetic patients are at increased risk of events than non-diabetic ones, including increased risk of death, a characteristic also observed in surgical procedures.

Hyperglycemia is a condition that enhances the proliferation of smooth muscle cells and fibroblasts, which are histological markers of the restenosis process. It also negatively influences vascular reactivity, inducing endothelial and platelet dysfunction. Therefore, strict metabolic control should be the norm.

The use of drug-eluting stents in diabetic patients significantly reduces the frequency of restenosis, although it did not reduce the frequency of death or myocardial infarction in the general population in large clinical trials. Some registries and sub-studies have shown a reduction of these events in diabetic individuals⁷⁹.

Diabetic patients with renal dysfunction deserve special attention. In elective cases, adequate hydration before the procedure, use of the smallest possible volume of contrast, in addition to contrasts with low osmolarity or isosmolar ones should be the norm in order to prevent the development of contrast-induced nephrotoxicity. Metformin should be discontinued 48 hours before the procedure due to the risk of developing lactic acidosis⁸⁰.

Full author list

Alexandre Alessi, Alexandre Vidal Bonfim, Andrea A Brandão, Audes Feitosa, Celso Amodeo, Claudia Rodrigues Alves, David P. Brasil, Dilma do SM Souza, Eduardo Barbosa, Fernanda Marciano Consolim-Colombo, Flávio Borelli, Francisco Helfenstein Fonseca, Heno F. Lopes, Hilton Chaves, Luis Aparecido Bortolotto, Luis C. Martin, Luiz Cesar Nazário Scala, Marco Antonio Mota-Gomes, Marcus Vinícius Bolívar Malachias, Maria Cristina Izar, Marília Izar Helfenstein Fonseca, Mário Fritsch Toros Neves, Nelson Siqueira Morais, Oswaldo Passarelli Jr, Paulo Cesar Veiga Jardim, Paulo Roberto Toscano, Roberto Dischinger Miranda, Roberto Franco, Roberto Tadeu Barcellos Betti, Rodrigo Pinto Pedrosa, Rui Povoa, Sérgio Baiocchi Carneiro, Thiago Jardim, Weimar Kunz Sebba Barroso.

References

• 1. Sociedade Brasileira de Hipertensão. Sociedade Brasileira de Cardiologia. Sociedade Brasileira de Nefrologia VI Diretrizes brasileiras de hipertensão. Arq Bras Cardiol. 2010;95(1 supl.1):1-51.
• 2. American Diabetes Association. Standards of medical care in diabetes - 2013.Diabetes Care. 2013,36 Suppl 1:S11-66.
• 3. Deedwania PC. Blood pressure control in diabetes mellitus: is lower always better and how low should it go? Circulation. 2011;123(24):2776-8.
• 4. International Diabetes Federation Atlas SG: Prevalence and Projections, 2010 and 2030.[Cited in 2012 Jul 24]. Available from : http://www.diabetesatlasorg/content/diabetes-and-impaired-glucose-tolerance 2010
• 5. Garcia-Touza M, Sowers JR. Evidence-based hypertension treatment in patients with diabetes. J Clin Hypertens (Greenwich).2012;14(2):97-102.
• ⁶
  Sociedade Brasileira de Diabetes. Atualização 2011. Algoritmo para o tratamento do diabetes tipo 2. Posicionamento oficial SBD nº 3, 2011. [Acesso em 2012 maio 10]. Disponível em: http://clinade.com.br/arquivos/17.pdf
• 7. Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, et al; Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375(9733):2215-22.
• 8. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al; The task force for the management of arterial hypertension of the European Society of Hypertension. The task force for the management of arterial hypertension of the European Society of Cardiology.2007 Guidelines for the management of arterial hypertension.The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007;28(12):1462-536.
• 9. Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, et al. Insulin resistance in essential hypertension. N Engl J Med. 1987;317(6):350-7.
• 10. Kannel WB, McGee DL.Diabetes and cardiovascular risk factors: the Framingham study. Circulation. 1979;59(1):8-13.
• 11. Hafner SM, Lehto S, Ronnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339(4):229-34.
• 12. Inzuchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M,et al; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care.2012;35(6):1364-79.
• 13. Guzmán JR, Lyra R, Aguilar-Salinas CA, Cavalcanti S, Escaño F, Tambasia M, et al; ALAD Consensus Group. Treatment of type 2 diabetes in Latin America: a consensus statement by the medical associations of 17 Latin American countries. Latin American Diabetes Association. Rev Panam Salud Publica. 2010;28(6):463-71.
• 14. van den Born BJ, Hulsman CA, Hoekstra JB, Schlingemann RO, van Montfrans GA. Value of routine funduscopy in patients with hypertension: systematic review. BMJ. 2005;331(7508):73.
• 15. Cuspidi C, Ambrosioni E, Mancia G, Pessina AC, Trimarco B, Zanchetti A; APROS Investigators. Role of echocardiography and carotid ultrasonography in stratifying risk in patients with essential hypertension: the Assessment of Prognostic Risk Observational Survey. JHypertens. 2002;20(7):1307-14.
• 16. Hsu CC, Brancati FL, Astor BC, Kao WH, Steffes MW, Folsom AR, et al. Blood pressure, atherosclerosis, and albuminuria in 10,113 participants in the atherosclerosis risk in communities study. J Hypertens. 2009;27(2):397-409.
• ¹⁷
  National Institute for Health and Clinical Excellence (NICE). NICE clinical guideline 127. Hypertension: clinical management of primary hypertension in adults. Methods, evidence and recommendations. [Cited in 2012 Aug 10]. Available from: http://www.nice.org.uk/nicemedia/live
• 18. Van Buren PN, Toto RD. The pathogenesis and management of hypertension in diabetic kidneydisease.Med Clin North Am. 2013;97(1):31-51.
• 19. Satirapoj B. Nephropathy in diabetes. Adv Exp Med Biol. 2012;771:107-22.
• 20. Garg R, Williams ME. Diabetes management in the kidney patient. Med Clin North Am.2013;97(1):135-56.
• 21. Phipps MS, JastreboffAM, Furie K, Kernan WN. The diagnosis and management of cerebrovascular disease in diabetes.CurrDiab Rep. 2012;12(3):314-23.
• 22. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903-13.Erratum in Lancet. 2003 Mar 22;361(9362):1060.
• 23. Hu G, Sarti C, Jousilahti P, Peltonen M, Qiao Q, Antikainen R, et al. The impact of history of hypertension and type 2 diabetes at baseline on the incidence of stroke and stroke mortality.Stroke. 2005;36(12):2538-43.
• 24. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA.Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function.Arch Neurol. 2004;61(5):661-6.
• 25. Petrova M, Prokopenko S, Pronina E, Mozheyko E.Diabetes type 2, hypertension and cognitive dysfunction in middle age women. J Neurol Sci. 2010;299(1-2):39-41.
• 26. American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care. 2003;26(12):3333-41.
• 27. Rein P, Beer S, Saely CH, Vonbank A, Drexel H. Prevalence of impaired glucose metabolism in individuals with peripheral arterial disease. Int J Cardiol. 2010;144(2):243-4.
• 28. Makdisse M, Pereira Ada C,Brasil DdeP, Borges JL, Machado-Coelho GL, Krieger JE, et al; Projeto Corações do Brasil e Comitê de Doença Arterial Periférica da Sociedade Brasileira de Cardiologia - SBC/FUNCOR. Prevalência e fatores de risco associados à doença arterial periférica no Projeto Corações do Brasil. Arq Bras Cardiol. 2008;91(6):370-82.
• 29. Escobedo J, Rana JS, LombarderoMS, Albert SG, Davis AM, Kennedy FP, et al; BARI 2D Study Group. Association between albuminuria and duration of diabetes and myocardial dysfunction and peripheral arterial disease among patients with stable coronary artery disease in the BARI2D study. Mayo Clin Proc.2010;85(1):41-6.
• 30. Morillas P, Cordero A, Bertomeu V, Gonzalez-Juanatey JR, Quiles J, Guindo J, et al; Prevalence of Peripheral Arterial Disease in Patients with Acute Coronary Syndrome (PAMISCA) Investigators. Prognostic value of low ankle-brachial index in patients with hypertension and acute coronary syndromes. J Hypertens.2009;27(2):341-7.
• 31. Wright GA, Ang DS, Stonebridge PA, Belch JJ, Struthers AD. Left ventricular hypertrophy is present in one-half of newly-diagnosed peripheral arterial disease patients. J Hypertens.2007;25(2):463-9.
• 32. Sheehan P.Peripheral arterial disease in people with diabetes:consensus statement recommends screening. Clinical Diabetes.2004;22(4):179-80.
• 33. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, FowkesFG, TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg. 2007;33 Suppl 1:S1-75.
• 34. Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression from hypertension to congestive heart failure.JAMA. 1996;275(20):1557-62.
• 35. Kawaguchi M, Techigawara M, Ishihata T, Asakura T, Saito F, Maehara K, et al. A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained frompatients with diabetes mellitus with and without hypertension. Heart Vessels. 1997;12(6):267-74.
• 36. Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation. 2007;115(25):3213-23.
• 37. McNulty PH, Louard RJ, Deckelbaum LI, Zaret BL, Young LH. Hyperinsulinemia inhibits myocardial protein degradation in patients with cardiovascular disease and insulin resistance. Circulation. 1995;92(8):2151-6.
• 38. Singal PK, Bello-Klein A, Farahmand F, Sandhawalia V. Oxidative stress and functional deficit in diabetic cardiomyopathy. AdvExp Med Biol. 2001;498:213-20.
• 39. Pierce GN, Dhalla NS. Heart mitochondrial function in chronic experimental diabetes in rats. Can J Cardiol. 1985;1(1):48-54.
• 40. Tanaka Y, Konno N, Kako KJ. Mitochondrial dysfunction observed in situ in cardiomyocytes of rats in experimental diabetes. Cardiovasc Res. 1992;26(4):409-14.
• 41. Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, et al; ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med.2010;362(17):1575-85.
• 42. Sociedade Brasileira de Diabetes (SBD). Diretrizes da Sociedade Brasileira de Diabetes - 2009. [Citado em 2012 maio 10]. Disponível em http://www.diabetes.org.br/attachments/diretrizes09_final.pdf
• 43. Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, et al; European Association for Cardiovascular Prevention & Rehabilitation. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32(14):1769-818.
• 44. Handelsman Y,Mechanick JI, Blonde L, Grunberger G, Bloomgarden ZT, Bray GA, et al; AACE Task Force for Developing Diabetes Comprehensive Care Plan. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract.2011;17 Suppl 2:1-53.
• 45. Sposito AC, Caramelli B, Fonseca FA, Bertolami MC, Afiune Neto A, Souza AD, et al.; Sociedade Brasileira de Cardiologia. IV Diretriz brasileira sobre dislipidemias e prevenção da aterosclerose. Arq Bras Cardiol. 2007;88(supl 1):1-18.
• 46. Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med. 1999;341(6):427-34.
• 47. Stevens VJ, Obarzanek E, Cook NR, Lee IM, Appel LJ, Smith West D, et al; Trials for the Hypertension Prevention Research Group. Long-term weight loss and changes in blood pressure: results of the trials of hypertension prevention, phase II. Ann Intern Med. 2001;134(1):1-11.
• 48. Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. Bariatric surgery: systematic review and meta-analysis. JAMA. 2004;292(14):1724-37. Erratum in JAMA. 2005;293(14):1728.
• 49. Pimenta E, Gaddam KK, Oparil S, Aban I, Husain S, Dell'Italia LJ, et al. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Hypertension. 2009;54(3):475-81.
• 50. Murphy MH, Nevill AM, Murtagh EM, Holder RL. The effect of walking on fitness, fatness and resting blood pressure: a meta-analysis of randomised, controlled trials. Prev Med. 2007;44(5):377-85.
• 51. Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, et al; American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology; American Heart Association Stroke Council; American Heart Association Council on Cardiovascular Nursing; American College of Cardiology Foundation. Sleep apnea and cardiovascular disease: an American Heart Association/american College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health).Circulation. 2008;118(10):1080-111.
• 52. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al; Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267-78.
• 53. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al; Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-81.
• 54. Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, et al; Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy of cholesterol-lowering therapy in 18 686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117-25.
• 55. Food and Drug Administration (FDA). Drug safety communication: important safety label changes to cholesterol-lowering statin drugs. [Cited in 2012 Feb 28]. Available from: http://www.fda.gov/DrugSafety/ucm293101.htm
• 56. Jun M, Foote C, LvJ, Neal B, Patel A, Nicholls SJ, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375(9729):1875-84.
• 57. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR; FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366(9500):1849-61.Erratum in Lancet. 2006;368(9545):1415, Lancet. 2006;368(9545):1420.
• 58. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety considerations with fibrate therapy. Am J Cardiol.2007;99(6A):3C-18C.
• 59. American Diabetes Association. Standards of medical care in diabetes - 2012. Diabetes Care.2012;35 Suppl 1:S11-S63.
• 60. Schernthaner G, Barnett AH, Betteridge DJ, Carmena R, Ceriello A, Charbonnel B, et al. Is the ADA/EASD algorhitm for the management of the type 2 diabetes (January 2009) based on evidence or opinion? A Critical Analysis. Diabetologia. 2010;53(7):1258-69.
• 61. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al; American Diabetes Association; European Association for the Study of Diabetes. Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2009;52(1):17-30.
• 62. Hodbard HW, Jellinger OS, Davidson JA, Einhorn D, Garber AJ, Grunberger G, et al. Statement by an American Association of Clinical Endocrinologists / American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15(6):540-59.
• 63. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-72.
• 64. Aronow WS. What should the blood pressure goal be in patients with hypertension who are at high risk for cardiovascular disease? Hosp Pract (1995). 2012;40(4):28-32.
• 65. Turnbull F, Neal B, Algert C, Chalmers J, Chapman N, Cutler J, et al; Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials. Arch Intern Med. 2005;165(12):1410-9.
• 66. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic:theAnthypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981-97.
• 67. Tuomilehto J, Rastenyto D, Birkenhager WH, Thijs L, Antikainen R, Bulpitt CJ, et al, Effects of calcium channel blockers in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators.N Engl J Med. 1999;340(9):677-84.
• 68. McFarlane S, Sowers JR.Cardiovascular endocrinology 1: aldosterone function in diabetes mellitus: effects on cardiovascular and renal disease. J ClinEndocrinolMetab. 2003;88(2):516-23.
• 69. Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, et al.Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998;351(9118):1755-62.
• 70. Major cardiovascular events in hypertensive patients randomized to doxazosinvzchlortalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group. JAMA. 2000;283(15):1967-75.
• 71. Psaty BM, Smith NL, Siscovick DS, Koepsell TD, Weiss NS, Heckbert SR, et al.Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA.1997;277(9):739-45.
• 72. Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ, et al; European Society of Hypertension. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens. 2009;27(11):2121-58.
• 73. Roussel R,Hadjadj S,Pasquet B,Wilson PW, Smith SC Jr, Goto S, et al. Thiazolidinedione use is not associated with worse cardiovascular outcomes: a study in 28,332 high risk patients with diabetes in routine clinical practice: brief title: Thiazolidinedione use and mortality. Int J Cardiol. 2012 May 4. [Epub ahead of print]
• 74. Tzoulaki I, Molokhia M, Curcin V, Little MP, Millett CJ, Ng A, et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ. 2009;339:b4731.
• 75. Mizoguchi M,Tahara N,Tahara A,Nitta Y, Kodama N, Oba T, et al. Pioglitazone attenuates atherosclerotic plaque inflammation in patients with impaired glucose tolerance or diabetes a prospective, randomized, comparator-controlled study using serial FDG PET/CT imaging study of carotid artery and ascending aorta. JACC Cardiovasc Imaging.2011;4(10):1110-8.
• 76. Naka KK, Papathanassiou K, Bechlioulis A, Pappas K, Kazakos N, Kanioglou C, et al. Effects of pioglitazone and metformin on vascular endothelial function in patients with type 2 diabetes treated with sulfonylureas. Diab Vasc Dis Res. 2012;9(1):52-8
• 77. Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al; SYNTAX Investigators. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med.2009;360(10):961-72.
• 78. Macaya C, García-García HM, Colombo A, Morice MC, Legrand V, Kuck KH, et al. One-year results of coronary revascularization in diabetic patients with multivessel coronary artery disease. Sirolimus stent vs. coronary artery bypass surgery and bare metal stent: insights from ARTS-II and ARTS-I. Eurointervention. 2006;2(1):69-76.
• 79. Daemen J, Kuck KH, Macaya C, LeGrand V, Vrolix M, Carrie D, et al; ARTS-II Investigators. Multivessel coronary revascularization in patients with and without diabetes mellitus: 3-year follow-up of the ARTS-II (Arterial Revascularization Therapies Study-Part II) trial. J Am Coll Cardiol. 2008;52(24):1957-67.
• 80. Levine GN, Bates ER, Blankenship JC,Bailey SR, Bittl JA, Cercek B, et al; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44-122.

I brazilian position statement on arterial hypertension and diabetes mellitus

Departament of Arterial Hypertension of the Brazilian Society of Cardiology by the authors

Publication Dates

• Publication in this collection
  05 July 2013
• Date of issue
  June 2013