Should Race be Used as a Factor in Hypertensive Treatment?

The origin of Race-based Guidelines for Hypertension:

Race-based diagnosis and treatment in medicine has become an increasingly contentious topic in the past few years, from re-evaluating the use of race-modified GFR in calculating renal function to use of racial categorization in pulmonary function testing of lung function. In the above areas, poor study design and essentialist racist assumptions led to adoption and perpetuation of different scales for White and African American patients without a sound scientific basis. For instance, the initial studies suggesting that African Americans had higher Creatinine levels (and therefore lower GFR) were potentially confounded by the muscle mass of the patients in the sample, and thus, not related to race, but to class and occupation.  The case of treating hypertension with different medications based on race is more contemporary, and relies on a more well-designed study.

The ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) was a double-blind study of over 30,000 patients comparing the effects of Chlorthalidone, Amlodipine, and Lisinopril over 4-8 years with the outcome measures of combined fatal CHD (coronary heart disease) or non-fatal myocardial infarction, and subgroup analysis of black patients.

The ALLHAT found the following:

• Higher relative risk of stroke and combined CVD with Lisinopril compared to Chlorthalidone for black patients

• Mean follow-up systolic blood pressure of 4 mm HG higher in blacks with Lisinopril compared to Chlorthalidone

Per the authors, these changes reflect “poorer BP response with ACE inhibitors in black patients.” Overall, the authors concluded that thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and recommended this as first-line anti-hypertensive therapy.

These findings were replicating among other large studies. The AASK study (African American Study of Kidney Disease and Hypertension) found ACE inhibitors were not as effective at lowering blood pressure in black patients, though they did prevent progression of kidney disease. As a result of these two major trials, as recently as 2017 the ACC/AHA (American College of Cardiology/American Heart Association) recommended black patients with no comorbidities receive either a thiazide or CCB as initial therapy, and non-black patients can receive ACE, thiazide or CCB as initial therapy. The JNC8 (Eight Joint National Committee in 2014) and ISHB (International society on Hypertension in Blacks) similarly recommended a race-based approach to hypertension treatment. In short, these societies targeted their recommendations to optimize treatment for black patients based on scientific data.

Investigating the underlying biology of racial differences

Is there a biological basis for potential increased response of black patients to thiazide or CCB monotherapy, and worse response to ACE inhibitors? There numerous studies pointing to a distinct hypertensive phenotype in African Americans. One key hypothesis is that African American patients are more prone to salt retention (i.e. higher salt-sensitivity), and as a result, have lower circulating levels of renin.

The story goes, less renin, less ability of ACE inhibitors to work on the renin-angiotensin-aldosterone system (RAS) to lower blood pressure. This begs the question: what is the origin of this particular subtype of hypertension? Here are a few hypotheses and the underlying pathophysiology that could explain them: 

• Historical – One speculative hypothesis is that the slave trade led to “limited access to water favoring the survival of persons who were avid sodium retainers and accelerating gene selection for sodium retention.” There is at best, mixed data to support this hypothesis[1], and lack of access to data to determine salt environments in Africa or the Americas between the 16th -19th centuries. The proposed mechanism would be as follows:

• Salt sensitive individual (due to geography in salt-poor environments or due to historical factors such as slave trade): Salt load --> Increase in Norepinephrine --> Activation of renin --> RAS activation

  Over time, the body would reach a different set point for RAS activation, and the increase activation would lower renin levels in the blood.

• Non-biologic – Obesity is a known driver of hypertension, which may confound the relationship between hypertension and race

  Obesity --> Insulin resistance --> Salt-sensitivity

• Genetic – Polymorphisms for the ACE gene and the angiotensinogen (ATG) gene, as well as other genetic variations have been shown to explain some differences in rates of hypertension between BAA and non-BAA. Similarly, there are genes related to the Atrial natrurietic peptide (ANP) and renal sodium channel that may play a role in increase salt-sensitivity among African Americans.

Suppose that there are differences in salt-sensitivity among black and non-black patients, from a combination of acquired and genetic factors. Does it follow that ACE inhibitors would not help African Americans as much?  Turns out that even in patients with low-renin levels, while ACE inhibitors may not do as well lowering blood pressure, they still exert important effects such as endothelial dysfunction, attenuate proteinuria, and reduce renal injury. In brief, according to Williams (2014), “there is no evidence of reduced efficacy for ACEI or ARB therapy on clinical outcomes in African Americans.” As recently as 2014, the author recommended dual therapy for initial BP management for African Americans.

From theory to clinical practice

Do the benefits of thiazide or CCB monotherapy hold up in real practice? A retrospective observational study sought to answer this question by comparing prescribing differences and HTN control in BAA (Black African American) vs. non-BAA patients aged 18 to 85 on 1- or 2-drug regimens. What were the findings?

• More BAA were prescribed thiazides as monotherapy, in keeping with the guidelines.

• BAA had worse control of hypertension compared with non-BAA for both 1- and 2-drug regimens.

• More frequent follow-up was associated with better hypertension control among BAA

As an observational study, it is hard to completely eliminate confounding variables. Still, the authors raise the important question: given the higher fourfold higher prevalence of CKD among BAA, might delayed use of ACE/ARB medications in early CKD lead to persistence of such a disparity?

The editorial by Flack and Buhnerkempe offers a thoughtful synthesis of the data with attention to the realities of practice.

The JNC8 offers the following tool for titrating combination therapy.

Summary:

Many scientific studies have found distinct physiological differences in salt-sensitivity and response to blood pressure treatment between White and African American patients. Such differences likely represent a combination of social, genetic, and environmental causes. In regards to treatment, the largest study (ALLHAT) found thiazides less harmful than ACE inhibitors in African Americans, but only for monotherapy. However, in clinical practice, there are more differences within racial groups than between racial groups on multiple medications. Given the higher prevalence of CKD in African Americans, guidelines are moving in the direction of starting most patients with hypertension on combination therapy with both ACE/ARB (for renal protection) and CCB or combination ACE/ARB and diuretic for those with BP greater than 20/10mm Hg above goal.

Guideline summary from Different Associations:

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) blood pressure guideline recommends calcium channel blockers and thiazide diuretics as first-line agents for Non-Hispanic African American adults with hypertension who do not have heart failure or renal disease, along with an added emphasis for the use of antihypertensive medications from two or more different classes

The International Society of Hypertension in Blacks (ISHIB) recommends combination therapy with a CCB plus a renin-angiotensin blocking agent (preferably angiotensin receptor blocker [ARB]) as first-line treatment for NH Black patients with hypertension

For Black adults with hypertension, the JNC 8 recommended a thiazide-type diuretic or CCB as initial treatment.

References:

1. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group; The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.  Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).   JAMA. 2002;288(23):2981-2997. doi:10.1001/jama.288.23.2981

• Flack JM, Buhnerkempe MG. Race and Antihypertensive Drug Therapy: Edging Closer to a New Paradigm. Hypertension. 2022 Feb;79(2):349-351. doi: 10.1161/HYPERTENSIONAHA.121.18545. Epub 2022 Jan 12. PMID: 35020461.

• Holt HK, Gildengorin G, Karliner L, Fontil V, Pramanik R, Potter MB. Differences in Hypertension Medication Prescribing for Black Americans and Their Association with Hypertension Outcomes. J Am Board Fam Med. 2022 Jan-Feb;35(1):26-34. doi: 10.3122/jabfm.2022.01.210276. PMID: 35039409.

• Mancia G, Kreutz R, Brunström M, Burnier M, Grassi G, Januszewicz A, Muiesan ML, Tsioufis K, Agabiti-Rosei E, Algharably EAE, Azizi M, Benetos A, Borghi C, Hitij JB, Cifkova R, Coca A, Cornelissen V, Cruickshank JK, Cunha PG, Danser AHJ, Pinho RM, Delles C, Dominiczak AF, Dorobantu M, Doumas M, Fernández-Alfonso MS, Halimi JM, Járai Z, Jelaković B, Jordan J, Kuznetsova T, Laurent S, Lovic D, Lurbe E, Mahfoud F, Manolis A, Miglinas M, Narkiewicz K, Niiranen T, Palatini P, Parati G, Pathak A, Persu A, Polonia J, Redon J, Sarafidis P, Schmieder R, Spronck B, Stabouli S, Stergiou G, Taddei S, Thomopoulos C, Tomaszewski M, Van de Borne P, Wanner C, Weber T, Williams B, Zhang ZY, Kjeldsen SE. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023 Dec 1;41(12):1874-2071. doi: 10.1097/HJH.0000000000003480. Epub 2023 Sep 26. Erratum in: J Hypertens. 2024 Jan 1;42(1):194. doi: 10.1097/HJH.0000000000003621. PMID: 37345492.

• Richardson SI, Freedman BI, Ellison DH, Rodriguez CJ. Salt sensitivity: a review with a focus on non-Hispanic blacks and Hispanics. J Am Soc Hypertens. 2013 Mar-Apr;7(2):170-9. doi: 10.1016/j.jash.2013.01.003. Epub 2013 Feb 19. PMID: 23428408; PMCID: PMC4574876.

• Verdecchia P, Grossmann E, Whelton P. 2023 ESH Guidelines. What are the main recommendations? Eur J Intern Med. 2023 Oct;116:1-7. doi: 10.1016/j.ejim.2023.07.034. Epub 2023 Aug 1. PMID: 37537030.

• Williams SF, Nicholas SB, Vaziri ND, Norris KC. African Americans, hypertension and the renin angiotensin system. World J Cardiol. 2014 Sep 26;6(9):878-89. doi: 10.4330/wjc.v6.i9.878. PMID: 25276290; PMCID: PMC4176798.

[1] Per the authors, “In question are the key tenets of the theory which implicate salt deficiency in the areas of Africa from which slaves originated, the trauma of the slave trade, and conditions in the Americas as triggers for unnatural genetic selection for renal sodium-retainers.”

Should Teachers Throw Out Grades?

Should schools throw out grades? It turns out there is not much evidence for grading: grades are proven to dampen creativity, courage, and enthusiasm. In the subgroup of Facebook, “Teachers for throwing out grades,” thousands of teachers propose strategies for dismantling grades. But what ought we to offer in place of them? In lieu of numerical grades, some un-grading practice include grading students on labor/effort, student self-assessment, or peer-assessment. I believe these have a place in the well-rounded classroom, and yet they beg the question: what are students assessing their peers on? 

To change our approach to assessment we must first change our approach to learning. Sadly, many classrooms premised on assessment focus so much time on skill-preparation, they can miss out on opportunities for students to ask questions, explore connections to other topics, or deepen their understanding of the current topic. When I’ve focused my classroom on preparing for a skill-based assessment, the lessons feel small, isolating, and unemotional.

In contrast, in my experience, the classes I learned the most from had a few characteristics in common: they were immersive, collaborative, and emotional.

Immersive – For some classes, this was immersion in a text or set of texts, or a deep philosophical question like “How do we measure scientific progress?” For other classes, the immersion was moving the classroom into the world. I recall an intensive care physician holding up bags of normal saline and asking student to calculate their sodium concentration.

Collaborative – In medicine, the concept of “team-based learning” has caught on across nearly all US medical schools. The traditional model of an individual taking isolated notes, and regurgitating them is starting to wane.

Emotional –My biggest failures in preparing students for exams is understanding their emotional reactions to taking tests. For some its dread, and for others its indifference or fatigue. I say “Because it will prepare you for a life a testing” both seriously and with a sinking heart.

When class is immersive, collaborative and emotional, I find students rarely even bring up grades, as there is a natural urge for students to go deeper and understand the material. Meanwhile, I notice grades become an extrinsic focus when the classroom becomes dull: “how worth it is it for me to complete this?” is what students seem to ask.

As I reflect on changing my grading model from a “traditional” (1-100 scale), to a standards-based (grading on a scale of 1-4 based on competency) and un-grading model (providing primarily written, formative feedback), I wonder how much I’m buying into the buzz around grading. When I learned the Saxophone, no-look passes in basketball, or how to do quantum mechanics, I didn’t care about grades. I cared about the teacher, the practice, and excellence in-and-of-itself. Yes, some grading may capture these pursuits, but it certainly won’t inspire them.

Site for "Teacher's Throwing Out Grades" https://www.facebook.com/groups/teachersthrowingoutgrades/

Powerpoint and Guided Notes: When Less is More

I had a powerpoint lesson set to go, with each slide meticulously planned with guided notes, pauses for student questions, which would allow me to move around the room and not be "tied" to the board. Then the projector broke. In my mind, there was utter chaos. How would students stay engaged with material if notes weren't guided? Turns out, they can do it. 

We went through the problems on the board, with simple pencil/paper, and paused to address misunderstandings. Without focusing so much on technology, I actually managed to make more eye contact with students and hold them accountable for engaging with the notes on the board. Also, there seemed to be something about the pace of writing notes as the teacher that worked, instead of having them up on a screen for students to copy. 

The class slowly got into a rhythm, with time for some stories interwoven with the notes (we were doing conditional probability and looking at the chance that someone with obesity gets diabetes versus someone without diabetes). 

One of the most senior teachers (a history teacher) at the school commented to me "I changed my whole curriculum over the past decade to focus on stories." Turns out it can work. Students wanted to know what percent of smokers go on to lung cancer, and what percent of obese people go on to get diabetes. 

For this particular class, it was the stories, the pacing, and the calmness that led to engagement, not technology, or micro-managing slides. I'm reminded of teaching classes with no computers, phones, instructional videos, or "polling questions" using devices while teaching in prisons. Somehow students still learn.

The Hidden Curriculum in High School Education

he concept of a "hidden curriculum" became popularized about a decade ago in medical education. As I understand it, the "hidden curriculum" is the idea that the dominant values of Western medicine (a focus on disease, pathophysiology, and patient compliance) are what is "really taught," despite small fringe efforts to teach about say, climate change and health, nutrition, or racial justice.

In high school education, I've never heard of anyone talk explicitly of "hidden curriculum." In fact, in my experience, the purpose of a curriculum never comes up. "It's to prepare students for college," or "it's to prepare students to enter the workforce." are the usual responses to why we are doing anything we do in the classroom.

One tough pill to swallow is that the more I repeat these platitudes to high school seniors, the more they believe them. The hidden part has become invisible to all -- we show up, turn in work, take tests, and hope this translates to a better life somewhere in a far off future. At the same time, students are actually quite more astute than this. When I put up the Mark Twain quote "Don't let school get in the way of your education," some students gave perplexed looks (where else do you get an education other than at school?) while others used it as an opportunity to open up about the "real" education outside of the school walls.

So what is this "real" education? What are we as schools avoiding talking about, in favor of "hard skills" of note-taking, test-taking, and behavioral compliance?

1. Who are we responsible to other than ourselves?

2. What does friendship mean?

3. What does it take to stand up for something you believe in?

4. What would you spend time learning about if you designed your own curriculum?

5. What does it mean to have a "good" conversation?

I'm sure there are dozens more. What I'm dancing around, and trying to make explicit is that I hope we as teachers make space to engage students in discussing ethics, virtues, and what matters.