Mitochondrial Haplogroup Association with Fasting Glucose Response in African Americans Treated with a Thiazide Diuretic

Hypertensive African Americans have ~50% response rate to thiazide diuretic treatment. This contributes to a high prevalence of uncontrolled high blood pressure. Here, we examine the role the mitochondrial genome has on thiazide diuretic treatment response in hypertensive African Americans enrolled in a clinical trial. Participants from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT, n= 4279) were genotyped using the Illumina Infinium Multi-Ethnic Beadchip. Haplotype groups were called using HaploGrep. We used linear regression analysis to examine the association between mitochondrial haplogroups (L, M, and N) and change in blood pressure and change in fasting glucose over 6 months and two years, respectively. The analysis revealed a null association between mitochondrial haplogroups M and N vs. L for each of the outcomes. In subgroup analysis, the L subclades L1, L2, and L3/L4 (vs. L0) were each inversely associated with fasting glucose response (p < 0.05). This discovery analysis suggests the mitochondrial genome has a small effect on fasting glucose but not blood pressure response to thiazide diuretic treatment in African Americans.

Renin‐Angiotensin Aldosterone System Inhibitors in Primary Prevention and COVID‐19

Background Considering the widespread risk of collider bias and confounding by indication in previous research, the associations between renin‐angiotensin aldosterone system (RAAS) inhibitor use and COVID‐19 remain unknown. Accordingly, this study tested the hypothesis that RAAS inhibitors influence the summation effect of COVID‐19 and its progression to severe outcomes. Methods and Results This nationwide cohort study compared all residents of Sweden, without prior cardiovascular disease, in monotherapy (as of January 1, 2020) with a RAAS inhibitor to those using a calcium channel blocker or a thiazide diuretic. Comparative cohorts were balanced using machine‐learning‐derived propensity score methods. Of 165 355 people in the analysis (51% women), 367 were hospitalized or died with COVID‐19 (246 using a RAAS inhibitor versus 121 using a calcium channel blocker or thiazide diuretic; Cox proportional hazard ratio [HR], 0.97; 95% CI, 0.74–1.27). When each outcome was assessed separately, 335 people were hospitalized with COVID‐19 (HR, 0.92; 95% CI, 0.70–1.22), and 64 died with COVID‐19 (HR, 1.22; 95% CI, 0.68–2.19). The severity of COVID‐19 outcomes did not differ between those using a RAAS inhibitor and those using a calcium channel blocker or thiazide diuretic (ordered logistic regression odds ratio, 1.01; 95% CI, 0.89–1.14). Conclusions Despite potential limitations, this study is among the best available evidence that RAAS inhibitor use in primary prevention does not increase the risk of severe COVID‐19 outcomes; presenting strong data from which scientists and policy makers alike can base, with greater confidence, their current position on the safety of using RAAS inhibitors during the COVID‐19 pandemic.

EXPRESS: A Rare Case of Persistent Hyperkalaemia

Hyperkalaemia is a common biochemical finding that can allude to pre-analytical or truly pathological causes. Here, we present a case of a 41-year-old female patient who has regularly presented with incidences of isolated hyperkalaemia since 2012, with otherwise normal renal function and no other associated symptoms. Investigations into the patient’s family history revealed similar biochemical findings in her brother and eldest son. Familial causes of hyperkalaemia were investigated and an eventual diagnosis of pseudo-hypoaldosteronism type 2C was established. This is a rare congenital renal tubular disorder, also known as Gordon syndrome, that can cause a characteristic triad of symptoms that include hyperkalaemia, metabolic acidosis and hypertension. The presence and severity of each of these symptoms is dependent upon the disease-causing mutation that occurs in WNK4, WNK1, CUL3 or KLHL3 genes. These mutations alter the regulation of sodium/chloride co-transporter (NCC) expression on the luminal membrane of the principal cells of the distal convoluted tubule, disrupting normal homeostatic regulation of electrolyte reabsorption and excretion. The resolution for treating this condition is the administration of a thiazide diuretic, which directly counteracts the effects of NCC co-transporter overexpression and consequently aims to resolve the symptoms that arise as a result of this aberrant signalling. The case described here uniquely presents an extremely rare pathogenic variant in the conserved acidic motif of WNK1 resulting in a clear electrolyte phenotype with no hypertension.

A Case Report of Atypical Hyponatremia Caused by Diarrhea Following a Course of Ferrous Sulfate Supplements

Hyponatremia, defined as a serum sodium level less than 135 mg/mL, can be euvolemic, hypovolemic, or hypervolemic. Its presentation can be subtle or severe depending on whether the hyponatremia is acute or chronic. This case investigates a geriatric patient who suffered diarrhea and hyponatremia following a course of ferrous sulfate pills for anemia treatment. Given that ferrous sulfate pills usually result in constipation, this presentation was abnormal. Literature review and comparison to prior atypical situations resulted in the conclusion that the patient’s diarrhea was likely a result of her Crohn’s diagnosis. The subsequent resulting hyponatremia was likely due to this diarrhea coupled with her prescription thiazide diuretic which can cause hyponatremia as a common side effect. This report allows for physicians to understand potential causes behind atypical electrolyte abnormalities in their patients and hence, find an effective treatment plan.

Treatment Patterns and Blood Pressure Control With Initiation of Combination Versus Monotherapy Antihypertensive Regimens

Many patients with hypertension require 2 or more drug classes to achieve their blood pressure (BP) goal. We compared antihypertensive medication treatment patterns and BP control between patients who initiated combination therapy versus monotherapy. We identified adults with hypertension enrolled in a US integrated healthcare system who initiated antihypertensive medication between 2008 and 2014. Patient demographics, clinical characteristics, antihypertensive medication, and BP were extracted from electronic health records. Antihypertensive medication patterns and multivariable adjusted prevalence ratios (PRs) of achieving the 2017 American College of Cardiology/American Heart Association guideline-recommended BP <130/80 mm Hg were evaluated for 2 years following treatment initiation. Of 135 971 patients, 43% initiated antihypertensive combination therapy (35% ACE [angiotensin converting enzyme] inhibitor (ACEI)-thiazide diuretics; 8% with other combinations) and 57% initiated monotherapy (22% ACEIs; 16% thiazide diuretics; 11% β blockers; 8% calcium channel blockers). After multivariable adjustment including premedication BP levels, patients who initiated ACEI-thiazide diuretic combination therapy were more likely to achieve BP <130/80 mm Hg compared with their counterparts who initiated monotherapy with ACEI (PR, 1.10 [95% CI, 1.08–1.12]), thiazide diuretic (PR, 1.21 [95% CI, 1.18–1.24]), β blocker (PR, 1.17 [95% CI, 1.14–1.20]), or calcium channel blocker (PR, 1.25 [95% CI, 1.22–1.29]). Compared with initiating monotherapy, patients initiating ACEI-thiazide diuretic combination therapy were more likely to achieve BP goals.