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.

Most insulting/funny sentence ever from a consulting doc

I have a new patient that I inherited from a former colleague. She came to me with a letter from her ophthalmologist addressed to the patient that she was suppposed to give to her primary care doctor and nephrologist.

Here is the money quote:

I am going to give you a copy of Harrison’s textbook to look for secondary causes of hypertension.

When the patient came in she didn’t have the book so I have no idea how to re-run her work-up of secondary hypertension (which had been done multiple times in the past).

Hey asshole, next time you have a bad outcome on one of your patients I’ll make sure I send you a copy of Clinical Ophthalmology: A Systematic Approach. What a dick.

I just gave the world’s greatest lecture on diabetic nephroapthy

It was incredible. The residents, who usually sleep through the second half of noon conference, were completely charged up and by the end of the lecture were holding up lighters and chanting my name. I dove from the stage and was passed around like a Rock God.
Here is the lecture in powerpoint format to download. You can also see the Slideshare but they mangle the animations so if you want to really feel the educational frenzy download the .ppt.

Calculating the urinary microalbumin to creatinine ratio

One of my high volume referring doctors uses a lab which does not calculate the microalbumin to cr ratio. It always stops me in my tracks when I see the values.

  1. To convert microalbum and urine creatinine to the useful ratio first make sure both values are expressed as mg/L or mg/ml
  2. Divide the microalbumin concentration by the creatinine concentration
  3. Multiply the resulting ratio by 1,000 to get mg albumin over grams creatinine
For example a patient had the following labs:

Microalbumn urine 5.6 mg/dL

Creatinine urine 91.2 mg/dL

Dividing the albumin by cr gives: 0.061

Multiply that by 1,000 to get 61 mg albumin/g creatinine

Hemoglobin A1c of 18.6

That corresponds to an average blood sugar of 486!
Six months and 1,500 mg of metformin later it is down to 8.4% corresponding to an average of 194. That 18.6 has got to be an error. Right? Right?
Unfortunately for her GFR is 30 mL/min.
No metformin for you.

iPhone, Android: Fight

Different data from the iPhone, Blackberry: Fight! from a few months ago but the same conclusion.
This battle is over! And the iPhone has won.
From Larvalabs:

Our two best selling games have been ranked and are currently ranked pretty highly on that hard to find list of paid apps. RetroDefense was #1 for a while and is currently around #12 with a perfect 5 star rating. Battle for Mars is currently #5 overall with a 4.5 star rating. Both of these games are selling for $4.99, which is on the upper end of the price range. Finally, both of these games have been featured by Google in the market app and on the Android website. So with all this in mind, here’s our daily Android sales for this August (these numbers include sales from our other two apps, but they barely register):

That’s a $62.39 daily average. Very difficult to buy the summer home at this rate.

So how much do we spend on routine daily labs?

Apparently a crap load:

Several studies have identified the overuse of daily lab testing and how certain interventions can effectively reduce tests ordered. A study by Miyakis et al. examined the effects of disclosing lab test costs on the frequency at which healthcare providers ordered these tests. 24,482 laboratory tests were ordered before the intervention (mean 2.96 tests/patient/day). Among those, roughly 70% were not considered to have contributed towards management of patients (mean avoidable 2.01 tests/patient/day). After costs of tests were disclosed, the avoidable tests/patient/day were significantly decreased (mean 1.58, p = 0.002), but containment of unnecessary ordering of tests gradually waned during the semester after the intervention. (1) A study by Kumwilaisak et al. examined how the implementation of formal guidelines effected how laboratory tests were ordered. 1,117 patients were enrolled. After the institution of the guidelines, the number of laboratory tests decreased by 37% (from 64,305 to 40,877). Furthermore, this result was still present at 1 year. (3)