JAMA MARCH 18, 1998

Sodium Reduction and Weight Loss in the Treatment of Hypertension in Older Persons: A Randomized Controlled Trial of Nonpharmacologic Interventions in the Elderly (TONE)

Paul K. Whelton, Lawrence J. Appel, Mark A. Espeland, et al. for the TONE Collaborative Research Group

Bottom Line

The TONE trial demonstrated that reduced sodium intake and weight loss, either alone or in combination, are effective, safe, and feasible nonpharmacologic strategies for maintaining blood pressure control in older adults after the withdrawal of antihypertensive medication.

Key Findings

1. Sodium reduction significantly reduced the risk of the primary endpoint (a composite of high blood pressure, resumption of drug therapy, or cardiovascular events) compared with usual care (hazard ratio 0.69; 95% CI, 0.59-0.81; P<.001).

2. In obese participants, weight loss was independently associated with a reduced risk of the primary endpoint compared with those not assigned to weight loss (hazard ratio 0.70; 95% CI, 0.57-0.87; P<.001).

3. The combined intervention of sodium reduction and weight loss in obese participants yielded the greatest benefit, with a hazard ratio of 0.47 (95% CI, 0.35-0.64; P<.001) compared to the usual care group.

4. There was no significant difference in the frequency of cardiovascular events across the various treatment groups during the follow-up period.

Study Design

Design

RCT

Open-Label

Sample

975

Patients

Duration

29 mo

Median

Setting

Four academic centers

Population Men and women aged 60 to 80 years with hypertension controlled by a single antihypertensive medication.

Intervention Dietary sodium reduction, weight loss, or both, using behavioral counseling.

Comparator Usual care (lifestyle maintenance)

Outcome Diagnosis of high blood pressure at one or more follow-up visits, resumption of antihypertensive medication, or occurrence of a cardiovascular event.

Study Limitations

• The study was restricted to patients already well-controlled on a single antihypertensive agent, which may limit generalizability to patients with more severe or resistant hypertension.

• The trial was not specifically powered to detect differences in hard clinical cardiovascular outcomes, only the composite endpoint including medication resumption.

• Maintenance of lifestyle behavioral changes in the long-term setting outside of a controlled trial environment remains a challenge.

• The study relied on self-reported compliance and behavioral counseling, which may vary in effectiveness in real-world clinical practice.

Clinical Significance

TONE provided the first robust experimental evidence that lifestyle modifications can successfully allow a substantial proportion of older hypertensive patients to discontinue antihypertensive medication while maintaining blood pressure control, potentially avoiding medication-related side effects and reducing treatment costs.

Historical Context

At the time of publication, while nonpharmacologic interventions were frequently recommended for hypertension, high-quality, randomized evidence in older populations was sparse. TONE filled this evidence gap and became a landmark study supporting the incorporation of lifestyle modification into hypertension management guidelines for older adults.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

Based on the physiological changes associated with aging, why might older adults in the TONE trial show a more pronounced response to sodium restriction than younger populations?

Key Response

Older adults often exhibit reduced efficiency in the renin-angiotensin-aldosterone system (RAAS) and a decline in renal function (reduced GFR), which contributes to a 'salt-sensitive' phenotype. Reducing sodium intake directly mitigates the volume expansion that drives hypertension in this demographic, making it a foundational mechanism for blood pressure control without the need for increased pharmacological intervention.

Resident

A 72-year-old patient with Stage 1 hypertension currently controlled on a single medication expresses interest in 'getting off' their pills. According to the TONE protocol, what specific lifestyle milestones and monitoring parameters are necessary to safely attempt medication withdrawal?

Key Response

The TONE trial suggests that patients should achieve a target sodium intake of <1800 mg/day or a weight loss of at least 3.5 kg. Medication withdrawal should be done incrementally with frequent monitoring; 'failure' in the trial was defined as BP exceeding 150/90 mmHg or the occurrence of a cardiovascular event, providing a clear safety threshold for residents managing similar patients in a primary care setting.

Fellow

When interpreting the results of the TONE trial for a patient with comorbid heart failure with preserved ejection fraction (HFpEF), how does the 'additive' effect of sodium reduction and weight loss influence your subspecialty management compared to a single-intervention approach?

Key Response

The TONE trial demonstrated that the combination of weight loss and sodium reduction had the lowest hazard ratio for treatment failure (HR 0.47). In HFpEF, where volume management and metabolic health are paramount, this synergy is critical. The 'additive' benefit suggests that these nonpharmacologic interventions work through distinct but complementary pathways—hemodynamic unloading and improved insulin sensitivity/vascular compliance.

Attending

The TONE trial was pioneering in its focus on 'successful medication withdrawal' rather than just 'blood pressure reduction.' How should this paradigm shift influence our teaching of polypharmacy and the 'prescribing cascade' in geriatric medicine?

Key Response

TONE provides high-level evidence that nonpharmacologic therapy is not merely an adjunct but a primary 'deprescribing' tool. It allows attendings to teach that 'therapeutic success' in the elderly includes the reduction of medication burden and potential side effects (like orthostasis or electrolyte imbalances) while maintaining clinical targets, challenging the 'one-way' nature of HTN treatment.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

Evaluate the internal validity of using 'medication withdrawal' as a primary endpoint in TONE; how does the lack of a double-blind design for lifestyle interventions potentially bias the assessment of 'successful' blood pressure maintenance?

Key Response

Since lifestyle interventions are unblinded, both participants and investigators may have had a psychological bias toward 'succeeding' in the withdrawal phase, potentially leading to more rigorous home monitoring or better adherence during the withdrawal period itself. This 'Hawthorne effect' could overestimate the feasibility of these interventions in a real-world, non-study environment where such intensive follow-up is absent.

Journal Editor

As a reviewer, what concerns would you raise regarding the scalability of the intensive behavioral interventions (up to 4 months of weekly meetings) utilized in TONE, and does this limit the paper's editorial impact for a general clinical audience?

Key Response

A tough reviewer would flag the 'efficacy-effectiveness gap.' The resource-heavy nature of the TONE interventions—dietitians and health educators providing frequent sessions—is rarely available in standard clinical practice. Editors must weigh the high internal rigor against the low external validity for the average clinician who cannot provide this level of behavioral support to their patients.

Guideline Committee

Given that TONE demonstrated successful BP control in nearly 40% of the combined intervention group without meds, should current ACC/AHA guidelines be updated to include a specific 'structured withdrawal' algorithm for older adults with Stage 1 hypertension?

Key Response

Current ACC/AHA guidelines (2017) emphasize lifestyle as Class I, Level A evidence for prevention and initial treatment. However, they lack a formal 'exit ramp' for those already on meds. TONE provides the evidence base for a Class IIa or IIb recommendation regarding structured medication withdrawal under close supervision for patients who successfully implement significant lifestyle changes, potentially reducing the burden of polypharmacy in the elderly.

Clinical Landscape

Noteworthy Related Trials

1997

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Comparator

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Endpoint

Change in systolic and diastolic blood pressure

Key result: The DASH diet significantly reduced both systolic and diastolic blood pressure compared to the control diet.

2002

ALLHAT Trial

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Endpoint

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Key result: Thiazide-type diuretics were superior to other antihypertensives in preventing major cardiovascular outcomes.

2003

PREMIER Trial

n = 810 · JAMA

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Comprehensive lifestyle modification including DASH, weight loss, and exercise

Population

Adults with above-optimal blood pressure or stage 1 hypertension

Comparator

Established care and advice-only control groups

Endpoint

Change in systolic blood pressure at 6 months

Key result: Combined lifestyle interventions produced greater reductions in blood pressure and hypertension incidence than advice alone.

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