Tag: DASH

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Articles that changed the way I practice: Sodium intake, hypertension and mortality

I have long been skeptical towards the party line that salt intake is a driver of high blood pressure, as I wrote here and here. Though hypertension is nearly unheard of in primitive cultures with sodium intake below 50 mmol/day (1.6 g day), increasing sodium intake has modest effects on blood pressure. Three mm of systolic per 100 mmol of sodium (2.3 grams) according to the Intersalt Study (PDF). This 3 mm of systolic agrees with the change in blood pressure in the DASH-Sodium trial. Similar effect size has been documented in meta-analysis:
  • A 2002 meta-analysis by Lee Hooper of 11 trials of at least 6 months duration found a 1.1/0.6 mmHg reduction from a 35 mmol (810 mg) reduction in sodium intake.
  • A broader meta-analysis published in JAMA in 1998 looked at 114 trials and found a reduction of 3.9/1.9 in hypertensive patients and 1.2/0.3 in normotensive participants.
Despite these seemingly modest results all of the clinical practice guidelines on hypertension have adopted sodium restriction as a key part of blood pressure control:
My position when talking with patients about dietary modifications for high blood pressure had been to mention sodium restriction and weight loss but focus on the DASH diet (PDF) and exercise. But this strategy has recently evolved as I became aware of a pair of studies, one by Cook et al which strengthened the sodium argument and one by Larry Appel which weakened his own DASH research.
The Rise of Sodium
The article by Nancy Cook is a follow-up on the Trial of Hypertension Prevention I and II. These were randomized controlled trials of patients with high normal blood pressure which tried to determine which lifestyle modifications were effective. Patients randomized to sodium reduction were given individual and group counseling sessions on how to reduce sodium in the diet. After 18 months the patients in the TOHP I reduced sodium intake by 44 mmol/day (1 g sodium) and blood pressure fell 1.7/0.8 mmHg. In TOHP II, after 36 months, sodium intake was reduced by 33 mmol/day (750 mg of sodium) and blood pressure fell 1.2/0.7. The decreases in blood pressure in both studies are unimpressive.
Cook went back to these studies, 10 years after TOHP I and 5 years after the completion of TOHP II, and looked at the rate of cardiovascular events (primary outcome: MI , CVA, CABG, PTCA, CV Death). They found a 25% reduction in events in patients in the low sodium group (p=0.04) that increased to 30% reduction when the study was adjusted for baseline sodium excretion and weight. These results are incredible to me, modest reductions in sodium intake that were achieved through patient education had negligible effects on blood pressure but dramatic benefits on morbidity.

The strengths of this evidence comes from two lines of reasoning:
  1. It is a randomised trial. Even though the current data comes from an observational extension of the original RCT, this does not change the fact that we are looking at two groups that were orignially randomized.
  2. This is a study which looks cardiovascular events rather than blood pressure or other intermediate outcomes.
The fall of the DASH
The DASH Trial (Appel 1997) used a diet rich in fruits and vegetables to provide increased fiber and potassium along with other trace minerals. Low-fat dairy products provide increased calcium while keeping the diet low in saturated and total fat. Participants randomized to the DASH diet were served meals with 4-5 servings of fruit, 4-5 servings of vegetables, 2-3 servings of of low fat dairy and <25%>

The results were dramatic:
  • Decreased blood pressure of 5.5/3.0 mmHg
  • Decreased in hypertensives 11.4/5.5 mmHg
  • Maximal blood pressure response occurred after only 2 weeks

The primary weakness in the DASH trials is that I’m not going to provide my patients with all of their food. It is not a clincally relevent intervention. As physicians, all we can do is educate and cousel on diet. Appel did a follow-up study where he did just that and the DASH was no longer so impressive.
The PREMIER Trial randomized patients to three groups:
  1. Control group with no interventions
  2. Standard advice: 18 face-to-face meetings to go over weight loss, and strategies to reduce sodium and alcohol consumption
  3. Standard + DASH: 18 face-to-face meetings with the same contant as the standard group with additional counseling on adopting the DASH diet
Counseling resulted in significant weight loss of 5 kg in both experimental groups versus loss of 1 kg in the control group. There was no difference in physical activity, but physical fitness did improve from baseline all three groups. They didn’t find a reduction in alcohol or sodium intake however there was good separation in the potassium intake with the greatest increase in potassium in the DASH group as would be expected. Both of the experimental groups had greater reductions in blood pressure than the control group. 40% of the patients randomized to the Standard advice and 48% of the patients in the Standard + DASH were able to lower their blood pressure below 120/80. This difference was not statistically significant.

There was no improvement in blood pressure control with the addition of the DASH diet over counseling patients on established risk factors.
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Weight loss and blood pressure


Hmm, that’s an interesting question. When I counsel patients on controlling blood pressure I mention weight loss but don’t perseverate on it because of the general futility of of achieving lasting weight loss. Most diets deliver only modest weight loss and that weight loss is depressingly short lived:
The figure above is the primary results from a trial of various strategies to preserve weight loss. 1,685 patients were enrolled, only 1,032 lost the require 10 lbs to begin Phase 2. In Phase 2 patients were randomized to 1) minimal intervention 2) web-based interaction 3) monthly contact with an interventionist. Patients with monthly contact regained 3 lbs less than the patients with self-directed maintenance. Svetkey et al. Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. JAMA (2008) vol. 299 (10) pp. 1139-48 (PDF)

Second study looking at Weight Watchers compared to a self-help program for weight loss. Same pattern, modest weight loss followed by rebound to regain much of the lost weight. Heshka et al. Weight loss with self-help compared with a structured commercial program: a randomized trial. JAMA (2003) vol. 289 (14) pp. 1792-8 (PDF)

I focus my limited office time on changing patients’ diet to reduce blood pressure. I recommend the DASH diet (PDF) to all of my patients without significant metabolic bone disease or hyperkalemia because I believe the data shows that it is the most effective life-style intervention to ameliorate hypertension. Unfortunately those two exclusions (bone disease and potassium) exclude many of my patients. I usually don’t recommend the low sodium version of of DASH because I feel that the reduction in palatability is not supported by the rather modest additive effects (an additional 3 mmHg reduction in SBP). Most of my patients recognize that they eat too much and have been trying to reduce calories, and lose weight for years prior to seeing me. I feel that by discussing the DASH diet and not rehashing the same tired dietary advice that every doctor has been promoting, I provide them with a novel view of dietary changes that they are willing to try.

Still, I think The Kidney Group has an interesting question, what is more important weight loss or diet changes?

NephSAP recently reviewed hypertension. On page 98 they had this table which compared various lifestyle interventions and their effect on blood pressure:
Unfortunately they grouped diet and weight loss in one group so it does not allow me to separate out the effect of changing diet from changing weight. Regardless, the effect on blood pressure looks modest compared to the findings of the DASH diet or DASH sodium intervention. From the abstract of the DASH-Sodium trial (PDF):

As compared with the control diet with a high sodium level, the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension, and 11.5 mm Hg lower in participants with hypertension.

The Archive published this meta-analysis (PDF) in 2008 looking at weight loss by diet or drugs with respect to mortality and blood pressure control.


They found that weight loss did result in blood pressure reductions but the reduction was modest. Additionally not all methods were equal, with silbutamide (Meridia) resulting in an increase in blood pressure despite being effective at reducing weight. They were unable to find any studies which showed a reduction in weight reducing mortality.

The above systemic review mentioned that the TONE study was one that was particularly well done. The TONE trial (PDF) was published in JAMA in 1998 and compared sodium restriction to weight loss to usual care in a two by two factorial design. The enrolled 585 obese patients to be randomized to either weight loss, no weight loss, salt restriction or not. Another 390 were randomized to either salt restriction or usual diet.
The investigators achieved nice separation of the groups with regard to weight loss. The study began with every patient weaning off their antihypertensive medication and the primary end-point was the fraction resuming their pharmacologic blood pressure medications and the time to resumption. Weight loss was more effective than no intervention and about equally efficacious as sodium restriction:

Note the lower starting blood pressure for sodium intake, this accounts for some of the difference in the effect on blood pressure.

Though TONE showed no difference between weight loss and sodium restriction, I feel that diet is probably more important because sodium restrictionis not the most effective dietary change to reduce blood pressure, the DASH diet is. I feel that if the TONE trial was rerun with the DASH diet replacing sodium restriction we might see that diet is more important than weight loss.

One thing I am doing in my clinic more and more is recommending bariatric surgery. Medical and behavioral changes have a poor track record at providing lasting and significant weight loss. Bariatric surgery shows lasting weight loss 10 years out and it allows patients to recover from hypertension and diabetes. Sjöström et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med (2004) vol. 351 (26) pp. 2683-93. (PDF)

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Its not the sodium intake its the sodium:potassium ratio

Don’t worry only about sodium intake (NYC, I’m looking at you) and its not just potassium intake (DASH diet in the cross-hairs). It’s all about the sodium potassium ratio. This is shown by Cook et al (PDF). during reanalysis of the Trial of Hypertension Prevention I and II. This trial had serial 24-hour urine collections done in 2,275 patients with pre-hypertension in the late 80’s and 90’s. The investigators looked at that data through the lens of 15 years of follow-up to determine the risk of cadiovascular events:

In observational analyses of the mean urinary excretion during 11⁄2 to 3 years, we found a suggested positive relationship of urinary sodium excretion and a suggested inverse relationship of urinary potassium excretion with risk of CVD, but neither was statistically significant when considered separately. Both measures strengthened when modeled jointly, with opposite but similar effects on risk. However, the sodium to potassium excretion ratio displayed the strongest and statistically significant association, with a 24% increase in risk per unit of the ratio that was similar for CHD and stroke and was consistent across subgroups.

Here is the key figure. Note in the graph the rate of events is presented on a log scale so the 2 indicates a rate 100 times the rate at zero.