This week, we tag along with NephMadness. It will be hard to stay impartial while discussing the role of angiogenic and antiangiogenic factors in severe preeclampsia prognosis.
🤔 Self managed BP control after pregnancy
Long-Term Blood Pressure Control After Hypertensive Pregnancy Following Physician-Optimized Self-Management: The POP-HT Randomized Clinical Trial (Kitt, JAMA 2023)
✏️ Salt reduction still lowers BP
Effect of Dietary Sodium on Blood Pressure: A Crossover Trial (Gupta, JAMA 2023)
We know reducing sodium intake lowers blood pressure (BP), but what is truly the effect in those with normal BP versus high BP? Those taking BP meds versus those who do not? In the Coronary Artery Risk Development in Young Adults (CARDIA)–SSBP trial (Gupta et al, JAMA 2023), the investigators enrolled 213 individuals either with normal BP or not, and either on BP meds with controlled or uncontrolled hypertension. They crossed over from the usual diet to low sodium (diet with 500 mg i.e. ~ 25 mmol sodium) and high sodium (with 2 bouillon packets, each containing 1100 mg of sodium added to the usual diet). The low sodium diet did result in lower BP in all subgroups, by about 5 - 6 mmHg SBP in the normotensive/controlled hypertension subgroups to about 9 - 190 mmHg SBP in the uncontrolled/untreated hypertension subgroups. Though the authors say these are not significantly different based on interaction p values, the subgroups are woefully underpowered to say that. Note that diet allocation was on alternate days, so this was not a randomized trial. Additionally - despite being provided food and daily phone calls, people on low sodium couldn’t stick to the provided saltless diet (24 hour urine sodium 1.7g rather than 0.5 g) and even the high sodium group couldn’t stomach the extra 2.2g bouillon (24 hour urine sodium went up from 4.6 to 5.5 rather than expected 6.8 g/day). So, an extremely low sodium diet does lower BP a bit, but it’s hard to achieve even if you are provided the food. Salt substitutes are so much more pragmatic!
Swapnil Hiremath
Pressure! Pushing down on me, pushing down on you: Should we be aggressively treating inpatient hypertension?
Hypertension Collection
New player in resistant hypertension?
This week we discussed aprocitentan, another endothelin receptor antagonist, this time being explored in the resistant hypertension arena - you know the #TenTweetNephJC drill, if you want a rapid catch up then here’s your place!
A New CHAPter in an Old Story
Acetaminophen and hypertension #TenTweetNephJC
The PATH-BP trial dropped - check out the results and the take from the #NephJC chats (in an <2 min summary)
Haircutting Hypertension: Barbers & Blood Pressure
The AHA/ACC guideline wrapup
Is 130 the new 140? The 2017 AHA/ACC Hypertension guidelines
The Pediatric Hypertension guidelines, #NephJC wrapup
Pediatric BP Guidelines: the YouTube edition
Hypertension Guidelines: Managing Blood Pressure in kids and teenagers
CV Risk scores: homework for #NephJC
#NephJC summary for HOPE-3 is Up
Check out the home page - great job by Peter Gallacher putting it together. See you all on April 26th or 27th. We hope to have an author online at the chat too. More soon!
Spironolactone primer
Resistant hypertension is an important clinical problem. It is commonly defined as inadequate blood pressure control despite use of three antihypertensive agents of different classes at optimal dosages; one of the three should be an appropriately dosed diuretic. About 10-15% of hypertensive patients have resistant hypertension.
The magical powers of aldosterone antagonists first started to be publicized in the late 90's and in 2003 Calhoun showed a dramatic effect among patients with resistant hypertension:
“A total number of 76 subjects were included in the analysis, 34 of whom had biochemical primary aldosteronism. Low-dose spironolactone was associated with an additional mean decrease in BP of 21 ± 21 over 10 ± 14 mm Hg at 6 weeks and 25 ± 20 over 12 ± 12 mm Hg at 6-month follow-up. The BP reduction was similar in subjects with and without primary aldosteronism and was additive to the use of ACE inhibitors, ARBs, and diuretics.”
This was backed up by additional observational data as part of the ASCOT trial experience. The investigators found dramatic efficacy from modest doses of spironolactone among the 1,411 patients that received spironolactone as a fourth line agent:
“During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: ±18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; P<0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. ”
The first randomized, placebo controlled trial in resistant hypertension was published in 2011. The ASPIRANT trial (PDF) showed a more modest, but still clinically significant reduction blood pressure.
An important caution when looking at spironolactone data is that it appears that black patients are more sensitive to increases in aldosterone, so one could predict more modest blood pressure improvements with spironolactone in a European population. See Tu et al. (Full text).
Another critical aspect of resistant hypertension is addressing non-adherence.
“A mass spectrometry urine toxicology screening of antihypertensive drugs reported that 53% of patients with resistant hypertension were non-adherent to treatment. Of these, 70% were incompletely adherent and 30% were completely non-adherent. Reduced adherence was not attributed to a particular antihypertensive class. Another urine analysis study found that 23% of patients referred for renal denervation were completely non- adherent to their prescribed antihypertensive treatment.”
This is why PATHWAY-2's attempt to measure minimize non-adherence is so important.
This week's chat on PATHWAY-2 represents the first randomized controlled trial against an active control group. The fact that aldosterone rises above other fourth line agents to provide meaningful advantages in the treatment of resistant hypertension is important.
We are coming to a new age in hypertension management. On November 9, at 2:00 PM at the AHA meeting in Orlando the SPRINT Trial results will be released. This will almost certainly result in a wave of more aggressive blood pressure control. Almost simultaneously we now have access to the first of the next generation potassium binders, patiromer. This brings the hope of avoiding the most frightening of the side effects from aldosterone antagonists, hyperkalemia. These three seemingly unrelated events are going to be major influences on the treatment of hypertension going forward.