Hypertension—A Treatable Component of the Cardiometabolic Syndrome: Challenges for the Primary Care Physician

Abstract

Patients with the cardiometabolic syndrome (CMS) have an adverse cardiovascular risk factor profile, placing them at increased risk of stroke, coronary artery disease, chronic kidney disease, and type 2 diabetes mellitus. Although no specific treatments for CMS are available per se, prompt recognition and treatment of the individual components of the condition can prevent or delay the development of comorbidities. Primary care physicians are ideally positioned to identify patients with CMS and implement early intervention strategies. Hypertension contributes to many complications of CMS, and rigorous blood pressure control will help to delay or prevent endorgan vascular damage. Achieving blood pressure control to current guideline standards should be eagerly sought in the majority of patients through a combination of lifestyle modifications and appropriate pharmacologic therapy. Antihypertensive drug choice should be personalized, taking into account the CMS determinants present and any compelling indications for specific agents. As an initial approach, a thiazide diuretic is suitable for most cases of uncomplicated hypertension, although many patients will require additional antihypertensives from other classes to achieve their blood pressure goal. It is predicted that, due to the increase in unhealthy lifestyles, the prevalence of CMS will rise in the coming years. Therefore, by meeting the challenge of attaining and maintaining blood pressure control in patients with CMS, primary care physicians have the unique opportunity to markedly improve the health of the nation.

The term “cardiometabolic syndrome” (CMS) has been used in the literature to describe a clustering of cardiovascular disease (CVD) risk factors, namely abdominal/visceral obesity, glucose intolerance (impaired glucose tolerance, impaired fasting glucose, and type 2 diabetes mellitus [T2DM]), hypertension, and dyslipidemia. ¹ , ² , ³ These abnormalities are produced through the interaction of genetic and environmental factors (modern atherogenic diets, physical inactivity, and overweight/obesity). Even though a unifying mechanism underlying CMS remains to be fully elucidated, insulin resistance/compensatory hyperinsulinemia is a key player. ⁴ Individuals who meet CMS criteria have a greatly increased risk of developing T2DM, coronary heart disease, stroke, and chronic kidney disease (CKD), as well as increased all‐cause and cardiovascular (CV) morbidity and mortality rates. ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵

Data collected in the National Health and Nutrition Examination Survey (NHANES) during 1999–2002 indicate that 39.0% of the adult population in the United States has the metabolic syndrome according to recent criteria proposed by the International Diabetes Federation (IDF) (Table I). ¹⁶ , ¹⁷ The prevalence increases with age, body mass index, level of hyperglycemia, and the presence of hypertension. ¹⁷ NHANES 1999–2002 data indicate that CMS is present in 58% of men and 63% of women aged 60–69 years, and in 65% of individuals with a body mass index ≥30 kg/m². ¹⁷ The prevalence of the syndrome is projected to increase further in coming years, with a parallel escalation in related health problems, as the population ages and as more individuals become overweight or obese. ¹⁸

Table I.

International Diabetes Federation Definition of the Metabolic Syndrome

Central Obesity (Waist Circumference)

Europids*

Men: ≥94 cm (≥37 in)

Women: ≥80 cm (≥31 in)

South Asians

Men: ≥90 cm (≥35 in)

Women: ≥80 cm (≥31 in)

Chinese

Men: ≥90 cm (≥35 in)

Women: ≥80 cm (≥31 in)

Japanese

Men: ≥85 cm (≥33 in)

Women: ≥90 cm (≥35 in)

Ethnic South and Central Americans: Use South Asian values until more specific data are available

Sub‐Saharan Africans: Use European values until more specific data are available

Eastern Mediterranean and Middle East (Arab) populations: Use European values until more specific data are available

Plus Any Two of the Following:

Raised triglycerides: ≥150 mg/dL (≥1.7 mmol/L) or specific treatment for this lipid abnormality

Reduced high‐density lipoprotein cholesterol: <40 mg/dL (<1.03 mmol/L) in men, <50 mg/dL (<1.29 mmol/L) in women, or specific treatment for this lipid abnormality

Raised blood pressure (BP): systolic BP ≥130 mm Hg or diastolic BP ≥85 mm Hg or treatment of previously diagnosed hypertension

Raised fasting plasma glucose: ≥100 mg/dL (≥5.6 mmol/L) or previously diagnosed type 2 diabetes mellitus; if >100 mg/dL (>5.6 mmol/L), oral glucose tolerance testing is strongly recommended but not necessary to define presence of the syndrome

*In the United States, National Cholesterol Education Program Adult Treatment Panel III values (men: >102 cm [>40 in]; women: >88 cm [>35 in]) 1 are likely to continue to be used for clinical purposes. Adapted with permission from International Diabetes Federation consensus worldwide definition of the metabolic syndrome. Available at: http:www.idf.orgwebdatadocsIDFMetasyndromedefinition.pdf. Accessed November 16, 2005. 16

Primary care physicians are in a strategic position to improve the nation's health by adopting an aggressive approach to screening for the various CMS component risk factors and managing each appropriately, thereby controlling the impending epidemic of diabetes and CV morbidity and mortality. ¹⁹ Management is complex, involving lifelong lifestyle and pharmacologic therapy in most patients. Targeting hypertension, a readily treatable component of CMS, should be a key initiative.

DEFINITION AND DIAGNOSIS: WHAT IS CMS?

The first challenge the primary care physician faces is to identify patients with CMS. Diagnostic criteria have been developed by various expert groups, including the World Health Organization (WHO), ²⁰ the National Cholesterol Education Program Adult Treatment Panel III (ATP‐III), ¹ the European Group for the Study of Insulin Resistance (EGIR), ²¹ the American Association of Clinical Endocrinologists (AACE), ²² and, most recently, the IDF. ¹⁶

The newly proposed IDF definition of the metabolic syndrome recognizes central/abdominal obesity (assessed by waist circumference) as an essential diagnostic criterion. This is based on the strong association of waist circumference with CVD and other CMS components ²³ and the probability that obesity has an early and pivotal role in the development of CMS. ² Importantly, specific waist circumference diagnostic thresholds vary according to gender and ethnicity, and recognizing established differences among different populations is essential (Table I). The IDF argued that this new criterion was designed to simplify the metabolic syndrome diagnosis, making it more accessible to clinicians and to future epidemiologic studies.

In addition to central obesity, the individual must have two or more of the following risk factors for a diagnosis of CMS: elevated triglycerides, low plasma high‐density lipoprotein cholesterol, hypertension, and elevated fasting plasma glucose (see Table I for defining levels). ¹⁶ Patients do not frequently present with all components of CMS simultaneously.

Each element of CMS can be easily assessed in clinical practice. For example, measuring waist circumference (at the level of the iliac crest at the end of normal expiration) with a tape measure usually indicates visceral obesity, and hypertension detection is readily available in the primary clinical setting. Since CMS is typically asymptomatic, affected individuals will normally be identified at routine medical examinations or when presenting with other complaints. If CMS is suspected at this consultation (e.g., because the patient is overweight and/or hypertensive), screening for other components of the syndrome is warranted.

Several other abnormalities cluster with CMS (Table II). These are probably related to insulin resistance/compensatory hyperinsulinemia but, according to the IDF, they are not essential for the metabolic syndrome diagnosis.

Table II.

Additional Factors Associated With the Cardiometabolic Syndrome

Lifestyle

Smoking

Sedentary behavior

Dyslipidemia

Increased apolipoprotein B

Decreased apolipoprotein A‐I

Small, dense low‐density lipoprotein

Increased apolipoprotein C‐III

Chronic, low‐grade inflammation

Increased C‐reactive protein

Increased white blood cell count

Increased interleukin‐6

Increased tumor necrosis factor α

Increased resistin

Decreased adiponectin

Prothrombotic state

Increased plasminogen activator inhibitor‐1

Increased fibrinogen

Increased serum viscosity

Vascular

Microalbuminuria

Increased asymmetric dimethylarginine

Polycystic ovary syndrome

Nonalcoholic fatty liver disease

Poor cardiorespiratory fitness

Hyperuricemia and gout

Increased homocysteine

Obstructive sleep apnea

Adapted with permission from Lancet. 2005;365:1415–1428. 3

A recently published joint statement by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes presents an interesting debate about CMS. ²⁴ The authors discuss the definition and even the very existence of the syndrome, its pathophysiologic origin, the cardiometabolic risk conferred by it vs. the risk associated with individual CMS components, and the available treatment alternatives. Whichever definition or approach to CMS is used, this controversy does indeed emphasize the importance of CV risk factors and their tendency to cluster in affected individuals and highlights the necessity for implementing preventive and therapeutic strategies. The ultimate goal is, of course, to prevent the progression of CVD and T2DM. This objective should be achieved by means of nonpharmacologic and pharmacologic approaches targeted at each one of the CV risk factors, without ignoring that they tend to cluster and that the presence of one risk factor should promote an active search for the others. Hopefully, in the future, research results will uncover a unifying hypothesis to help elucidate the ultimate cause of this worldwide pandemic, making it more feasible to design a single treatment strategy.

WHICH CLINICAL SEQUELAE ARE ASSOCIATED WITH CMS?

The next challenge for the physician is to appreciate and communicate to the patient the magnitude of the inherent risks of CMS. CV events (notably, coronary artery disease, sudden cardiac death, or stroke) are the main adverse clinical outcomes. ⁵ , ⁶ , ⁸ , ⁹ , ¹⁰ , ¹¹ This is not surprising given that coexistence of multiple CVD risk factors carries a greater susceptibility to CV morbidity and mortality than a disturbance in just one factor. The risk of a CV event is about two‐fold greater among individuals with CMS than those without it. ¹⁵ , ²⁵

CMS also predisposes to T2DM. This is important from a CVD standpoint because diabetes is regarded as a coronary risk equivalent, ¹ meaning that the likelihood of a first major coronary event among patients with diabetes is as high as a recurrent event among individuals with established heart disease. Patients with diabetes and CMS are thus at extremely high CVD risk. One report suggests that the incidence of CV events is five times higher among patients with diabetes and CMS than among patients with diabetes alone. ²⁶

Individuals with CMS are also susceptible to CKD, polycystic ovary syndrome, nonalcoholic fatty liver disease, cholesterol gallstones, asthma, obstructive sleep apnea, and some forms of cancer, particularly colon and breast cancer. ³ , ⁵ , ²⁷

THE ROLE OF HYPERTENSION IN CMS

Hypertension is a potent CVD risk factor. ²⁸ The relationship between blood pressure (BP) and risk of events is continuous, consistent, and independent; the higher the BP, the greater the probability of myocardial infarction, heart failure, stroke, and CKD. ²⁹ The CVD risk associated with hypertension escalates further when other risk factors are present, ³⁰ as in patients with CMS. In its early stages, hypertension‐related vascular and end‐organ damage is often subclinical, manifesting itself only when a catastrophic CV event occurs (such as myocardial infarction or stroke). The development of microalbuminuria may serve as an early indicator of widespread vascular damage, being not only a pressure‐dependent functional phenomenon in the glomerular vessels, but also reflecting endothelial dysfunction throughout the entire vascular system. ³¹ , ³² , ³³

Hypertension is tightly associated with obesity, a key element of CMS. Obesity and hypertension are characterized by a chronic low‐grade inflammatory state, as well as by activation of the renin‐angiotensin‐aldosterone system and sympathetic nervous axis. ³⁴ Obesity also causes marked structural changes in the kidneys that eventually lead to a loss of nephron function and further elevate arterial BP. ³⁴

Within the CMS, hypertension is defined as systolic BP (SBP) ≥130 mm Hg or diastolic BP (DBP) ≥85 mm Hg. ¹⁶ It is one of the most common components of CMS, being present in 84.2% of men and 76.7% of women with CMS (Figure 1), ³⁵ and contributes directly to many adverse clinical outcomes. Furthermore, early, subclinical signs of hypertension‐related cardiac, vascular, renal, and retinal damage are higher in hypertensive individuals with CMS than in those without the syndrome. ³⁶ , ³⁷

Figure 1.

Prevalence of select risk factors among subjects with the cardiometabolic syndrome. Men: waist circumference (WC) >40 in (≥102 cm), blood pressure (BP) ≥130/85 mm Hg, triglycerides (TG) ≥150 mg/dL (≥1.69 mmol/L), high‐density lipoprotein cholesterol (HDL‐C) ≤40 mg/dL (≤1.03 mmol/L), low‐density lipoprotein cholesterol (LDL‐C) ≥130 mg/dL (≥3.36 mmol/L), and fasting glucose (FG) ≥110 mg/dL (≥6.11 mmol/L). Women: WC >35 inches (>88 cm), BP ≥130/8S mm Hg, TG ≥150 mg/dL (≥1.69 mmol/L), HDL‐C ≤50 mg/dL (≤1.29 mmol/L), LDL‐C ≥130 mg/dL (≥3.36 mmol/L), and FG ≥110 mg/dL (≥6.11 mmol/L). Reproduced with permission from Am J Cardiol. 2003;91:1421–1426. ³⁵

WHAT IS THE GOAL OF BP MANAGEMENT?

The ultimate goal of antihypertensive therapy is to prevent, delay, or reverse BP‐related end‐organ vascular damage, thereby reducing the risk of CV morbidity and mortality. To achieve this most effectively, BP should be reduced to target levels specified in current guidelines. The current (Seventh) Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends an SBP goal of <140 mm Hg and a DBP goal of <90 mm Hg in the general population. ²⁸ A substantial proportion of patients with CMS, however, have diabetes or CKD; JNC 7 and the ADA recommend a goal of <130/80 mm Hg for such individuals. ²⁸ , ³⁸ Thus, the physician is challenged to be bold enough to adopt an intensive BP management strategy to achieve and maintain these BP goals and protect the patient against future morbidity and mortality.

A survey utilizing the Framingham algorithm to evaluate coronary risk in subjects with CMS participating in NHANES III (conducted during 1988–1994) estimated that controlling BP to normal levels (120–129/80–84 mm Hg) would prevent 28.1% of coronary events in men and 12.5% of events in women. ³⁵ Control to optimal levels (<120/80 mm Hg) was estimated to prevent 28.2% of coronary events in men and 45.1% of events in women. Additional clinical end point data are needed, however, to confirm these figures.

CMS patients with hypertension should be managed according to current guidelines, which comprise lifestyle modifications and pharmacologic therapy (Table III, Figure 2). ²⁸

Table III.

Lifestyle Modifications to Prevent and Manage Hypertension

Modification	Recommendation	≅SBP Reduction (mm Hg)
Weight reduction	Achieve and maintain normal body weight (BMI: 18.5–24.9 kg/m2).  For example:  Decrease portion sizes for meals, snacks  Reduce portion sizes or frequency of consumption of high‐calorie beverages  Reduce energy intake by 500 kcal/d	5–20/10 kg
Adopt DASH eating plan	Consume a diet rich in fruits, vegetables, and low‐fat dairy products with a reduced content of saturated and total fat	8–14
Dietary sodium reduction	Reduce dietary sodium intake to =100 mmol/d (2.4 g sodium or 6 g sodium chloride). High sodium intake is especially deleterious in overweight individuals	2–8
Physical activity	Engage in regular aerobic physical activities that raise the heart rate, such as brisk walking (=30 min/d, most days of the week)	4–9
Moderation of alcohol consumption	Limit consumption to ≤2 drinks/d (e.g., 24 oz beer, 10 oz wine, or 3 oz 80‐proof whiskey) in most men and to ≤1 drink/d in women and lighter‐weight persons	2–4
SBP=systolic blood pressure; BMI=body mass index; DASH=Dietary Approaches to Stop Hypertension. Adapted with permission from JAMA. 2003;289:2560–2572. 28

Figure 2.

Algorithm for the treatment of hypertension. SBP=systolic blood pressure; DBP=diastolic blood pressure; ACEl=angiotensin‐converting enzyme inhibitor; ARB=angiotensin receptor blacker; BB=β blocker; CCB=calcium channel blocker; Aldo ANT=aldosterone antagonist. Adapted with permission from JAMA. 2003;289:2560–2572. ²⁸

REDUCING BP THROUGH LIFESTYLE CHANGES

Therapeutic lifestyle changes are the cornerstone of CMS management. ¹⁶ JNC 7 provides specific recommendations for weight reduction, physical activity, and a healthy diet (restricted sodium intake, the Dietary Approaches to Stop Hypertension [DASH], and moderate alcohol consumption) to reduce hypertension (Table III). ²⁸ A realistic weight loss target is 5%–10% of initial weight over 1 year. ¹⁶ Losing 22 lb (10 kg) reduces SBP by 5–20 mm Hg in a large proportion of overweight individuals. ²⁸ Individuals should also be strongly counseled to stop smoking to reduce their overall CVD risk.

Lifestyle interventions can prevent the development of diabetes, a main consideration in patients with CMS. The Diabetes Prevention Program Research Group ³⁹ showed that an intervention consisting of weight loss plus regular physical activity reduced the incidence of newly diagnosed T2DM by almost 60% vs. placebo and was significantly more effective than metformin in prediabetic individuals with elevated fasting and postload plasma glucose levels. Recently published results from the same group showed that the prevalence of hypertension decreased significantly with 3 years of intensive lifestyle intervention. ⁴⁰ Likewise, a nonpharmacologic approach significantly increased the high‐density lipoprotein cholesterol level and reduced the cumulative incidence of the atherogenic low‐density lipoprotein phenotype B. Triglyceride levels fell in all treatment groups (lifestyle and metformin). Even though no differences in CVD incidence were statistically proven, it is likely that after a longer follow‐up period the benefits of modifying CV risk factors will translate into fewer CV events.

Motivating patients to maintain lifestyle changes as a means of long‐term BP control presents another challenge to the physician. For example, many patients find it difficult to adhere to weight reduction programs or they regain the lost weight after dismissal from clinical care. Continued observation and encouragement with combined lifestyle interventions and antihypertensive therapy can help patients attain their BP goal, making them more likely to adhere to lifestyle changes through positive reinforcement.

USE OF ANTIHYPERTENSIVE DRUGS

For patients who fail to achieve their BP goal through lifestyle changes alone, antihypertensive drug therapy may be required. Once a decision has been made to adopt a pharmacologic approach to hypertension management, the challenge is to select the most appropriate drug. Therapeutic alternatives for hypertensive patients with CMS include thiazide diuretics, β blockers, angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers. ²⁸ , ⁴¹ Antihypertensive drug selection should be tailored to the individual, taking into account the pathophysiologic determinants of CMS present and the presence of specific comorbid conditions, such as CKD, that are compelling indications for specific agents (Figure 2). ²⁸

Thiazide Diuretics

Thiazide diuretics are widely regarded as the cornerstone of antihypertensive drug therapy. The JNC 7 report recommends initial therapy with a thiazide diuretic in patients with mild‐to‐moderate hypertension not associated with other chronic CV diseases. ²⁸ At high doses, however, diuretics may cause untoward metabolic disturbances (e.g., hypokalemia, hyperuricemia, impaired glucose control, and increased insulin resistance), which are a concern in CMS patients. Combining a low dose of diuretic with another antihypertensive agent provides additive BP‐lowering efficacy and minimizes drug‐related, dose‐dependent side effects. ²⁸ Diuretic‐induced potassium depletion can be offset by coadministering an ACE inhibitor or ARB. ⁴² , ⁴³ , ⁴⁴

Beta Blockers

Beta blockers may have adverse effects on glucose homeostasis in patients with diabetes or obesity. ²⁸ , ⁴⁵ These problems are usually easily managed, however, and are not contraindications for β‐blocker use. ²⁸ Beta blockers have also been shown to predispose to weight gain in some population studies. ⁴⁶ , ⁴⁷ These potentially adverse effects need to be balanced against the proven benefits of β blockers in reducing CV risk. Beta blockers are especially beneficial in patients with ischemic heart disease. ²⁸

Calcium Channel Blockers

Since the effects of calcium channel blockers on lipid and glucose metabolism are predominantly neutral, they are appropriate for patients with CMS. Clinical outcome trials, such as the Hypertension Optimal Treatment (HOT) trial ⁴⁸ and the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) ⁴⁹ showed that calcium channel blockers are safe and effective in controlling BP and reducing CVD events in patients with diabetes. Side effects associated with vasodilatation, such as flushing, headache, and ankle edema, can be troublesome.

ACE Inhibitors

Several large clinical trials, including the Heart Outcomes Prevention Evaluation (HOPE), ⁵⁰ , ⁵¹ demonstrated that ACE inhibitors have cardioprotective and renoprotective properties beyond their effect on BP. These benefits extend to patients with diabetes. ⁵¹ ACE inhibitors have also been associated with a reduced incidence of T2DM in HOPE ⁵⁰ and in the Captopril Prevention Project (CAPPP). ⁵² The most common adverse effect of ACE inhibitors is a chronic dry cough.

Angiotensin Receptor Blockers

Renoprotection data from clinical trials, such as the Irbesartan Diabetic Nephropathy Trial (Figure 3), ⁵³ indicate that ARBs slow the progression of renal disease in patients with T2DM. ⁵⁴ , ⁵⁵ , ⁵⁶ Other outcome trials, including the Valsartan Antihypertensive Long‐Term Use Evaluation (VALUE), ⁵⁷ the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity‐Overall (CHARM‐Overall), ⁵⁸ and the Losartan Intervention For Endpoint Reduction in Hypertension study (LIFE), ⁵⁹ indicate that ARBs are also associated with a lower incidence of T2DM and could prevent CV events. ⁶⁰ The incidence of adverse effects with ARBs appears to be lower than with other currently available antihypertensive agents.

Figure 3.

Cumulative proportions of patients with the primary composite end point (doubling of baseline serum creatinine, development of end‐stage renal disease, or death from any cause) in 1715 patients with nephropathy due to type 2 diabetes treated with irbesartan 300 mg, amlodipine 10 mg, or placebo in the Irbesartan Diabetic Nephropathy Trial. Adapted with permission from N Engl J Med. 2001;345:851–860. ⁵³ Copyright ©2001 Massachusetts Medical Society. All rights reserved.

Combination Therapy

Clinical trials consistently show that most patients require two or more antihypertensive agents to reach BP goal. Most national and international hypertension management guidelines recognize the need for multidrug therapy ²⁸ , ³⁸ , ⁶¹ and some recommend initial treatment with a combination of two drugs in certain patients. For example, JNC 7 recommends considering initial treatment with two drugs in patients with SBP >20 mm Hg above goal or DBP >10 mm Hg above goal (i.e., all patients with stage 2 hypertension and some patients with stage 1 hypertension plus diabetes or renal disease). ²⁸ The International Society on Hypertension in Blacks (ISHIB) recommends combination therapy if BP is ≥15/10 mm Hg above goal. ⁶¹ The combinations may be given as individual prescriptions or as fixed‐dose formulations and should include a diuretic in almost all cases. ²⁸

Using fixed‐dose combinations containing two antihypertensive agents eases the process of BP control. For example, in a subgroup analysis of the Irbesartan/HCTZ Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial, ⁶² irbesartan/hydrochlorothiazide fixed combinations provided SBP goal achievement in 73% of CMS patients with SBP uncontrolled on antihypertensive monotherapy. ⁶³ Selecting efficacious, well tolerated, once‐daily combinations may also encourage patient compliance by minimizing dose‐dependent side effects and reducing pill burden. Such formulations are also cost‐effective.

MICROALBUMINURIA AND ANTIHYPERTENSIVE DRUG SELECTION

Microalbuminuria (urinary albumin excretion 30–300 mg/d) clusters with CMS, the prevalence being significantly higher among individuals with than without CMS (12.3% vs. 4.7%; p=0.004). ²⁷ In addition, microalbuminuria is present in 11%–17% of hypertensive patients without diabetes. ⁶⁴

The presence of microalbuminuria demands attention because it is associated with an increased CV risk in the general population. ⁶⁵ Furthermore, even albumin levels that are considered normal by present standards have been associated with CVD progression in a nonhypertensive diabetic population. ⁶⁶ Of the various abnormalities associated with CMS, microalbuminuria confers the strongest risk of CV death. ⁶⁷

The presence of microalbuminuria should not only alert the clinician about the presence of nephropathy, but also about the existence of generalized endothelial dysfunction, as microalbuminuria is a reflection of increased capillary permeability secondary to endothelial damage. ⁶⁸

Rigorous BP control is paramount to prevent the development and progression of microalbuminuria. Guidelines typically recommend a target of <130/80 mm Hg in patients with CKD using a regimen that includes an ACE inhibitor or ARB (i.e., antihypertensive agents with proven renoprotective properties). ²⁸ , ³⁸ , ⁶¹

CONCLUSIONS

With the expected explosion in prevalence of CMS as the number of obese and overweight individuals increases, the consequences of ignoring it are clear: a dramatic increase in CV morbidity and mortality, and an increase in diabetes and its complications. The downstream costs of these health care problems will be substantial. Early identification of individuals with CMS and management of each component risk factor will reap future rewards for the physician, the patient, and the health care provider.

Hypertension is a highly prevalent component of CMS that dramatically heightens the risk of stroke and accelerates the progression of atherosclerosis and renal disease, yet it is easily treated. By emphasizing the importance of a healthy lifestyle and making informed choices in drug selection, physicians can rise to the challenge of achieving goal BP in most CMS patients. Reducing BP to goal should translate into immense public health benefits by preventing future morbidity and mortality.

Disclosure:

Editorial assistance for the development of this manuscript was provided by Elaine Griffin, PhD, Envision Pharma, with the financial support of the Bristol‐Myers Squibb/Sanofi‐Synthelabo Partnership. Dr. Sowers has grants from the NIH (R01‐HL‐63904), the VA Merit Reward, AstraZeneca, and Novartis, and is on the Speaker's Bureau for Bristol‐Myers Squibb, Merck, and Novartis.