Preventing and Treating Hypertension with Diet (Part 2)

Guidelines for Hypertension – What Does Standard Treatment Look Like?

At the present time, standardized guidelines involving nonpharmacological and drug treatment approaches are applied globally to address the great burden of hypertension on individual health and global health care systems.

studiesThe relationship between hypertension and lifestyle factors, including obesity, high dietary salt intake, smoking, alcohol consumption, and physical inactivity, have been convincingly established, and thus several lifestyle modifications are indicated as the appropriate non-pharmacological treatment approach for patients with elevated blood pressure (BP) 1)Appel LJ, Champagne CM, Harsha DW, et al. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003;289(16):2083-2093. doi:10.1001/jama.289.16.2083. Current guidelines recommend that nonpharmacological approaches are initiated, independent of whether antihypertensive medications are indicated. Nonpharmacological therapy should be addressed in each and every patient with HTN. Lifestyle changes include dietary sodium restriction, moderation of alcohol consumption, weight reduction and maintaining an ideal body weight, regular physical activity, and a healthy diet. Studies show, for example, that hypertension is reduced upon adhering to the dietary recommendations by the so-called DASH-diet (Dietary Approaches to Stop Hypertension) 2)Siervo M, Lara J, Chowdhury S, Ashor A, Oggioni C, Mathers JC. Effects of the Dietary Approach to Stop Hypertension (DASH) diet on cardiovascular risk factors: a systematic review and meta-analysis. Br J Nutr. 2015;113(1):1-15. doi:10.1017/S0007114514003341. The effects of this and other diets on blood pressure will be discussed in detail in the following chapters.

Several clinical guidelines have been established in order to both detect and manage or treat hypertension. The goals are to optimally control elevated blood pressure and to reduce associated cardiovascular and renal morbidity and mortality 3)Chobanian AV, Bakris GL, Black HR, et al. 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):2560-2572. doi:10.1001/jama.289.19.2560. Unfortunately, hypertension still remains poorly controlled. Even with the pharmaceutical treatment currently available, global rates of uncontrolled blood pressure continue to rise 4)Kjeldsen S, Feldman RD, Lisheng L, et al. Updated national and international hypertension guidelines: a review of current recommendations. Drugs. 2014;74(17):2033-2051. doi:10.1007/s40265-014-0306-5.

While the European Society of Cardiology (ESC) adheres to the definition of hypertension as office systolic blood pressure values ≥140 mm Hg and/or diastolic blood pressure values ≥90 mm Hg (grade I), the American Heart Association considers patients with blood pressure levels of ≥130/80 mm Hg as hypertensive 5)Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71(6):1269-1324. doi:10.1161/HYP.0000000000000066. This is a reaction to the so-called SPRINT-Study 6)SPRINT Research Group, Wright JT, Williamson JD, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015;373(22):2103-2116. doi:10.1056/NEJMoa1511939 that found a 25% reduction of mortality and a 30% risk reduction of cardiovascular events in a group where systolic blood pressure was lowered below 120 mm Hg compared to a group that had the original target value of <140 mm Hg.

The ESC also recommends aiming at a reduction to the normal values of less than 130/80 mm Hg, but treatment should not be started before the diagnosis of grade I hypertension.

At grade II or III (≥160/100 mm Hg, or ≥180/110 mm Hg, respectively), or in patients with high-normal blood pressure levels and high cardiovascular risk, medication should be initiated immediately alongside lifestyle interventions. Grade I allows for a period of lifestyle modifications for several months until the indication for medication should be reconsidered. The HOPE-3 trial indicates drug treatment should only be offered if lifestyle changes were not adhered to or failed after attempts were exhausted and if the patients’ blood pressure is close to the hypertension diagnostic threshold of 140/90 mm Hg 7)Lonn EM, Bosch J, López-Jaramillo P, et al. Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016;374(21):2009-2020. doi:10.1056/NEJMoa1600175. Interestingly, the ESC guidelines dedicate only a short paragraph of approximately 250 words to the management of hypertension by diet. They state: “Lifestyle interventions can undoubtedly lower BP and in some cases CV risk […] but most patients with hypertension will also require drug treatment.” 8)Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018;36(10):1953-2041. doi:10.1097/HJH.0000000000001940

The ESC guidelines recommend, apart from some exceptions, an initial drug therapy with a combination of two drugs, usually an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in combination with a calcium channel blocker (CCB) or thiazide-type diuretic. In a second step, this treatment plan can be augmented to a triple combination.

What are the Possibilities and Limitations of Drug Therapy?

Law and colleagues 9)Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003;326(7404):1427. doi:10.1136/bmj.326.7404.1427 performed a meta-analysis of clinical trials on the efficacy of antihypertensive medication. They analyzed five groups of antihypertensive drugs, including thiazides, b-blockers, ACE inhibitors, angiotensin II, and calcium channel blockers. They concluded that the blood pressure lowering effects of these classes of medications were similar, with an average reduction of 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard doses. However, there were ethnic-specific responses to different medication. For example, b-blockers were less effective than thiazide diuretics in African American patients.

Another review 10)Wu J, Kraja AT, Oberman A, et al. A summary of the effects of antihypertensive medications on measured blood pressure. Am J Hypertens. 2005;18(7):935-942. doi:10.1016/j.amjhyper.2005.01.011 looked at 137 clinical trials with monodrug therapies and 28 clinical trials of combination drug therapies to differentiate the effects of common antihypertensive drugs. Monodrug therapy with ACE inhibitors showed a weighted average effect of lowering systolic and diastolic BP by 12.5/9.5 mm Hg; a1-blockers by 15.5/11.7 mm Hg; b-blockers by 14.8/12.2 mm Hg; calcium channel blockers by 15.3/10.5 mm Hg; thiazide diuretics by 15.3/9.8 mm Hg; and loop diuretics by 15.8/8.2 mm Hg. When two drugs were combined, the blood pressure lowering effect of the second medication, when compared to its effect as monodrug therapy, was 84% and 65% for systolic and diastolic blood pressure, respectively.

Antihypertensive drugs carry several contraindications. For example, diuretics (thiazides/thiazide-like) and b-blockers have to be used with caution in those with gout or asthma, while ACE inhibitors and angiotensin receptor blockers are contraindicated in pregnant women or women of child-bearing age without contraceptive methods in place.

Most importantly, several side effects are seen in the pharmacological-based treatments of hypertension.

For example, thiazides can lead to many unwanted issues including gastrointestinal symptoms, gout, hypokalemia and impairment of glucose tolerance 11)Sommerauer C, Kaushik N, Woodham A, et al. Thiazides in the management of hypertension in older adults – a systematic review. BMC Geriatr. 2017;17(Suppl 1):228. doi:10.1186/s12877-017-0576-3. ACE inhibitors may lead to loss of taste, chronic dry cough, hyperkalemia, angioedema, and renal failure 12)Regulski M, Regulska K, Stanisz BJ, et al. Chemistry and pharmacology of Angiotensin-converting enzyme inhibitors. Curr Pharm Des. 2015;21(13):1764-1775.. Both groups are suspected exert carcinogenic effects. A risk evaluation by the European Medicines Agency (EMA) and its Pharmacovigilance Risk Assessment Committee yielded the recommendation to inform all patients that hydrochlorothiazide (HCT) might cause skin cancer 13); last accessed: April 1, 2019. This recommendation is based on two Danish studies that show a cumulative dose-response relationship between HCT and non-melanoma skin cancer 14)Pedersen SA, Johannesdottir Schmidt SA, Hölmich LR, Friis S, Pottegård A, Gaist D. Hydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors: A nationwide case-control study. J Am Acad Dermatol. 2019;80(2):460-465.e9. doi:10.1016/j.jaad.2018.06.014. In 2018, a British study was published stating that the intake of ACE inhibitor increases lung cancer risk by 6% (compared to patients who were taking HCT) 15)Hicks BM, Filion KB, Yin H, Sakr L, Udell JA, Azoulay L. Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study. BMJ. 2018;363. doi:10.1136/bmj.k4209. However, data of this study are difficult to interpret, and there’s still more research needed in order to confirm a causal relationship between HCT, ACE inhibitors and certain types of cancer. b-blockers also have several side effects, such as bradycardia, dizziness, hyperglycemia, vascular claudication, and diarrhea 16)Barron AJ, Zaman N, Cole GD, Wensel R, Okonko DO, Francis DP. Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: recommendations for patient information. Int J Cardiol. 2013;168(4):3572-3579. doi:10.1016/j.ijcard.2013.05.068.

Finally, there are few clinical parameters that predict how an individual will respond to various drugs, whereas each patient group has shown improvement upon adopting and adhering to lifestyle modifications.

To summarize, the current guidelines emphasize the change of lifestyle habits such as physical activity and a healthy diet either before or alongside any medical treatment. Antihypertensive drugs are effective, but they bear the risk of adverse effects. The question we have to ask is what can be achieved by diet alone to bypass the disadvantages of drugs and still reduce cardiovascular risk due to hypertension?

This article is part of the series “Preventing and Treating Hypertension with Diet“.