Concerns About the Joint National Committee on Prevention,Detection,Evaluation,and Treatment of High Blood Pressure 8 Blood Pressure Panel Member Recommendations and Their Relevance to Metabolic Syndrome

Hypertension is both a common and important cardiovascular (CVD) risk factor. There are 72 million persons in the United States with hypertension, and hypertension leads to myocardial infarction, congestive heart failure, stroke, and renal failure if not detected early and treated aggressively. ^1,2 The relationship between naturally occurring blood pressure and risk is linear down to a blood pressure of around 115/75 mmHg. Above 115/75 mmHg, for each increase of 20 mmHg in systolic blood pressure (SBP) or 10 mmHg in diastolic blood pressure (DBP), the risk of major CVD and stroke events doubles.

The development of hypertension may be preceded by a prehypertensive condition that is characterized by abnormal cardiovascular reactivity to behavioral and environmental challenges. This includes cold water immersion, ³ mental stress, ^4,5 as well as isometric and dynamic physical activity. ^6,7 Using this logic and data from clinical and observational studies, the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) made recommendations published in 2003 that blood pressure treatment goals for all persons be 140/90 mmHg, and 130/80 mmHg for those with chronic renal disease and diabetes mellitus. ⁸ They established a category of prehypertension for persons with blood pressures of 120–139/80–89 mmHg.

In a major departure from these recommendations, the panel members appointed to write JNC 8 have published a new set of guidelines. ⁹ In this context, it is important to note that these are not official guidelines from National Heart, Lung, and Blood Institute (NHLBI). In June, 2013, NHLBI announced that it would discontinue developing clinical guidelines, including those in progress. ¹⁰ Rather, NHLBI would partner with selected organizations to develop guidelines. The panel originally selected to pursue JNC 8 decided to publish their recommendations independently. ⁹

The major goal of the panel members appointed to write JNC 8 was to take a “rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults.” ⁹ The panel limited its analysis to original publications of randomized clinical trials (RCTs) of multicentered hypertension studies that had at least 2000 participants and that had important health outcomes that included total mortality, CVD mortality, other serious cardiac outcomes, or measures of end-stage renal disease.

What are the major differences from JNC 7? In persons aged 60 years or older, the JNC 8 panelists felt that the strongest evidence led to a recommendation to increase the target SBP from less than 140 to less than 150 mmHg. ⁹ In hypertensive persons aged 30–59 years of age, the panelists again, on the basis of their evaluation of the best evidence, recommend treating to a DBP goal of less than 90 mmHg. ⁹ A goal of less than 140/90 mmHg is recommended for adult hypertensives less than 60 years of age with diabetes or with nondiabetic chronic kidney disease, a change from the 130/80 mmHg recommended by JNC 7.

The JNC 8 panelists vary on the basis of their recommendations, although they do grade the strength of their positions. In some instances, they make their recommendations based on the above strict criteria for study inclusion, but for other recommendations, they rely on “expert opinion.” ⁹ For example, the JNC 8 panelists believe that there is insufficient evidence in hypertensives younger than 60 years of age for a SBP goal, or for those younger than 30 years for a diastolic or a systolic goal, “so the panel recommends a blood pressure goal of less than 140/90 mmHg for those groups based on expert opinion.” Of the 10 different recommendations (including one “Corollary Recommendation”), seven are judged to be based on “Expert Opinion–Grade E.” ⁹ For the practicing physician, the plethora of recommendations, all based on differing levels of evidence, may be confusing.

Although all panel members agreed with most recommendations, some of the panelists disagreed with the recommendation for SBP goals of less than 150 mmHg for those 60 years or older, believing that a change from the JNC 7 recommendation for SBP of less than 140 mmHg for those 60 years of older is not warranted by the evidence. ¹¹ If broadly adopted, the recommendations of the JNC 8 panel members would have a major impact on the treatment of hypertension. More than one-half of hypertensives in the United States are aged 60 years or older. ^1,2 An increase of the target SBP from less than 140 to less than 150 mmHg in these persons and from 130 to 140 mmHg for diabetics and persons with chronic renal disease would impact tens of millions of hypertensives.

From a population perspective, less aggressive SBP treatment of older persons will translate into higher blood pressures in this group. Because this is the group that is at highest risk for CVD, changes in SBP goals will result in more CVD events. Age increases risk for CVD events, so differences in CVD risk do not justify different targets for those persons older or younger than 60 years of age. The same concern pertains to hypertensives with diabetes or chronic nondiabetic kidney disease. The dissenting JNC 8 panelists point out that, if followed, these recommendations could reverse the decade-long decline in CVD events, especially stroke mortality. ¹¹

There is clinical trial evidence that supports the more aggressive treatment of patients 60 years or older to SBP goals of approximately 140 mmHg. In the Systolic Hypertension in the Elderly Program (SHEP), antihypertensive treatment of persons 60 years or older with systolic hypertension showed benefit of treating SBP to a goal between 140 and 145 mmHg. ¹² In the Hypertension in the Very Elderly Trial (HYVET), a benefit was found of an SBP target of <150 mmHg on health outcomes, including mortality in persons aged 80 years or older. ¹³ A recently published study of 1111 participants without established CVD disease and with SBP ≥150 mmHg found that intensive blood pressure treatment aimed at lowering SBP to <130 mmHg reduced left ventricular hypertrophy, clinical risk of CVD events, and all-cause death more than those treated to a SBP of <140 mmHg. ¹⁴ The decision by the JNC 8 panelists to only include multicenter RCTs of at least 2000 participants in their deliberation led them to not include smaller trials, meta-analyses of smaller trials, and highly suggestive observational trials. Three recent guidelines from Europe and Canada as well as from the American College of Cardiology and the American Society of Hypertension recommend a SBP goal of less than 140 mmHg, particularly in persons aged 80 years or younger. ^{15 –19}

Metabolic syndrome is a constellation of metabolic risk factors that identifies individuals with an increased risk of CVD. The criteria for metabolic syndrome, as identified by the modified National Cholesterol Education Panel Adult Treatment Panel III (NCEP ATP III), include abdominal obesity, an atherogenic dyslipidemia manifest as elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C), blood pressure of ≥130/85 mmHg, and impaired fasting glucose. ²⁰ Insulin resistance is a consequence of abdominal obesity that often leads to elevated blood glucose levels and consequently to elevated insulin levels, which in turn may lead to other components of metabolic syndrome, such as an abnormal lipid profile and hypertension. The importance of metabolic syndrome is that it confers at least a two-fold increased risk of CVD and at least five-fold increased risk for subsequent diabetes. ^{21 –24} The age-adjusted prevalence of metabolic syndrome in the general US population is 24.0% for men and 24.3% for women. ²⁵

Treatment of hypertension may have both deleterious and beneficial effects on the other components of metabolic syndrome depending on the agent(s) chosen; treatment with different antihypertensive drug classes has varied effects on glucose and lipid metabolism. ²⁶ Thiazide use in hypertension has been associated with the development of glucose intolerance and diabetes. ²⁷ Studies suggest that the probability of worsening glucose metabolism, and the development of new diabetes after thiazide initiation is associated with increasing body mass index. ²⁸ Thiazide use also results in small increases in total and low-density lipoprotein cholesterol (LDL-C) and triglycerides and decreases in HDL-C. These changes are more pronounced with high-dose thiazides.

Nonselective or β₁-selective β-blockers may lead to decreased insulin sensitivity in hypertensive patients. ^29,30 On the other hand, β-blockers, such as carvedilol, that cause vasodilatation may not have these deleterious effects on insulin sensitivity and glucose metabolism. ^31,32 The effects of β-blockers on lipid metabolism also vary according to β-blocker type. Nonselective β-blockers modestly increase serum triglycerides and tend to lower HDL-C, whereas cardioselective β₁-blockers and those without intrinsic sympathomimetic activity have qualitatively similar but less pronounced effects. Vasodilating β-blockers appear to have even smaller deleterious effects on lipids.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) may exert beneficial effects on glycemic control through a variety of mechanisms related to the inhibition of angiotensin II. ^{33 –35} These agents may be particularly useful in patients with microalbuminuria to slow the progression of renal disease, another important consequence of hypertension. While there may be some small differences among different classes of calcium channel blockers (CCBs), there is little net effect of these agents on glucose or lipid metabolism. ^36,37 The α-antagonists generally appear to improve glucose and lipid metabolism in diabetic and nondiabetic patients, but the increase in cardiovascular end points in the ALLHAT study with doxazosin suggests that until there is evidence to the contrary, this class of antihypertensive should not be used as first-line agents. ^38,39

Thus, treating patients with metabolic syndrome with hypertension would be expected to have either beneficial or deleterious effects on other components of metabolic syndrome, depending upon the agent chosen. Overall, the benefits of treating hypertension outweigh the metabolic consequences of the different antihypertensive drugs. It is prudent, however, to choose an antihypertensive that does not result in the development of a new disease, such as diabetes, that may require its own treatment.

There are other concerns about the recommendations of the JNC 8 panelists. Less aggressive blood pressure treatment in those 60 years or older might lead to a less aggressive approach toward promoting nonpharmacologic treatments of hypertension (particularly for those with SBP in the 140–150 range), including weight loss, salt reduction, exercise, limiting alcohol consumption, and efforts at smoking cessation. All of these have beneficial effects on not only CVD events, but on other components of metabolic syndrome as well.

Although well studied compared with many other clinical disorders, there are insufficient data from large multicenter clinical trials to create evidence-based recommendations that cover all age groups, including those with and without diabetes and/or chronic renal disease, and that include recommendations for both systolic and diastolic hypertension. Lacking this information, recommendations for some groups will necessarily reflect expert opinion that takes into consideration observational studies and meta-analyses as well as clinical trials. Currently, there is insufficient evidence to recommend an increase in the SBP goal in persons aged 60 years or older from less than 140 mmHg to less than150 mmHg by the JNC 8 majority panelists. Making such a proposal has the potential of jeopardizing the tremendous progress that has been made in reducing the risk of CVD in persons older than 60 years of age. This change also has the potential to negatively impact other components of the metabolic syndrome.