A bidirectional Mendelian randomization study supports causal effects of kidney function on blood pressure.
Yu Zhi,Coresh Josef,Qi Guanghao,Grams Morgan,Boerwinkle Eric,Snieder Harold,Teumer Alexander,Pattaro Cristian,Köttgen Anna,Chatterjee Nilanjan,Tin Adrienne
Blood pressure and kidney function have a bidirectional relation. Hypertension has long been considered as a risk factor for kidney function decline. However, whether intensive blood pressure control could promote kidney health has been uncertain. The kidney is known to have a major role in affecting blood pressure through sodium extraction and regulating electrolyte balance. This bidirectional relation makes causal inference between these two traits difficult. Therefore, to examine the causal relations between these two traits, we performed two-sample Mendelian randomization analyses using summary statistics of large-scale genome-wide association studies. We selected genetic instruments more likely to be specific for kidney function using meta-analyses of complementary kidney function biomarkers (glomerular filtration rate estimated from serum creatinine [eGFRcr], and blood urea nitrogen from the CKDGen Consortium). Systolic and diastolic blood pressure summary statistics were from the International Consortium for Blood Pressure and UK Biobank. Significant evidence supported the causal effects of higher kidney function on lower blood pressure. Based on the mode-based Mendelian randomization method, the effect estimates for one standard deviation (SD) higher in log-transformed eGFRcr was -0.17 SD unit (95 % confidence interval: -0.09 to -0.24) in systolic blood pressure and -0.15 SD unit (95% confidence interval: -0.07 to -0.22) in diastolic blood pressure. In contrast, the causal effects of blood pressure on kidney function were not statistically significant. Thus, our results support causal effects of higher kidney function on lower blood pressure and suggest preventing kidney function decline can reduce the public health burden of hypertension.
Concordance Between Blood Pressure in the Systolic Blood Pressure Intervention Trial and in Routine Clinical Practice.
Drawz Paul E,Agarwal Anil,Dwyer Jamie P,Horwitz Edward,Lash James,Lenoir Kristin,McWilliams Andrew,Oparil Suzanne,Rahbari-Oskoui Frederic,Rahman Mahboob,Parkulo Mark A,Pemu Priscilla,Raj Dominic S,Rocco Michael,Soman Sandeep,Thomas George,Tuot Delphine S,Whelton Paul K,Pajewski Nicholas M
JAMA internal medicine
Importance:There are concerns with translating results from the Systolic Blood Pressure Intervention Trial (SPRINT) into clinical practice because the standardized protocol used to measure blood pressure (BP) may not be consistently applied in routine clinical practice. Objectives:To evaluate the concordance between BPs obtained in routine clinical practice and those obtained using the SPRINT protocol and whether concordance varied by target trial BP. Design, Setting, and Participants:This observational prognostic study linking outpatient vital sign information from electronic health records (EHRs) with data from 49 of the 102 SPRINT sites was conducted from November 8, 2010, to August 20, 2015, among 3074 adults 50 years or older with hypertension without diabetes or a history of stroke. Statistical analysis was performed from May 21, 2019, to March 20, 2020. Main Outcomes and Measures:Blood pressures measured in routine clinical practice and SPRINT. Results:Participant-level EHR data was obtained for 3074 participants (2482 men [80.7%]; mean [SD] age, 68.5 [9.1] years) with 3 or more outpatient and trial BP measurements. In the period from the 6-month study visit to the end of the study intervention, the mean systolic BP (SBP) in the intensive treatment group from outpatient BP recorded in the EHR was 7.3 mm Hg higher (95% CI, 7.0-7.6 mm Hg) than BP measured at trial visits; the mean difference between BP recorded in the outpatient EHR and trial SBP was smaller for participants in the standard treatment group (4.6 mm Hg [95% CI, 4.4-4.9 mm Hg]). Bland-Altman analyses demonstrated low agreement between outpatient BP recorded in the EHR and trial BP, with wide agreement intervals ranging from approximately -30 mm Hg to 45 mm Hg in both treatment groups. In addition, the difference between BP recorded in the EHR and trial BP varied widely by site. Conclusions and Relevance:Outpatient BPs measured in routine clinical practice were generally higher than BP measurements taken in SPRINT, with greater mean SBP differences apparent in the intensive treatment group. There was a consistent high degree of heterogeneity between the BPs recorded in the EHR and trial BPs, with significant variability over time, between and within the participants, and across clinic sites. These results highlight the importance of proper BP measurement technique and an inability to apply 1 common correction factor (ie, approximately 10 mm Hg) to approximate research-quality BP estimates when BP is not measured appropriately in routine clinical practice. Trial Registration:SPRINT ClinicalTrials.gov Identifier: NCT01206062.
The Malaria-High Blood Pressure Hypothesis: Revisited.
Nwokocha Chukwuemeka R,Bafor Enitome E,Ajayi Olutayo I,Ebeigbe Anthony B
American journal of hypertension
Malaria etiologies with pathophysiological similarities to hypertension currently constitute a major subject of research. The malaria-high blood pressure hypothesis is strongly supported by observations of the increasing incidence of hypertension in malaria-endemic, low- and middle-income countries with poor socioeconomic conditions, particularly in sub-Saharan African countries. Malnutrition and low birth weight with persistent symptomatic malaria presentations in pregnancy correlate strongly with the development of preeclampsia, gestational hypertension and subsequent hypertension in adult life. Evidence suggest that the link between malaria infection and high blood pressure involves interactions between malaria parasites and erythrocytes, the inflammatory process, effects of the infection during pregnancy; effects on renal and vascular functions as well as effects in sickle cell disease. Possible mechanisms which provide justification for the malaria-high blood pressure hypothesis include the following: endothelial dysfunction (reduced nitric oxide (NO) levels), impaired release of local neurotransmitters and cytokines, decrease in vascular smooth muscle cell viability and/or alterations in cellular calcium signaling leading to enhanced vascular reactivity, remodeling, and cardiomyopathies, deranged homeostasis through dehydration, elevated intracellular mediators and proinflammatory cytokine responses, possible genetic regulations, activation of the renin-angiotensin-aldosterone system mechanisms and renal derangements, severe anemia and hemolysis, renal failure, and end organ damage. Two key mediators of the malaria-high blood pressure association are: endothelial dysfunction (reduced NO) and increased angiotensin-converting enzyme activity/angiotensin II levels. Sickle cell disease is associated with protection against malaria infection and reduced blood pressure. In this review, we present the state of knowledge about the malaria-blood pressure hypothesis and suggest insights for future studies.
Blood pressure during endovascular treatment under conscious sedation or local anesthesia.
Samuels Noor,van de Graaf Rob A,van den Berg Carlijn A L,Nieboer Daan,Eralp Ismail,Treurniet Kilian M,Emmer Bart J,Immink Rogier V,Majoie Charles B L M,van Zwam Wim H,Bokkers Reinoud P H,Uyttenboogaart Maarten,van Hasselt Boudewijn A A M,Mühling Jörg,Burke James F,Roozenbeek Bob,van der Lugt Aad,Dippel Diederik W J,Lingsma Hester F,van Es Adriaan C G M,
OBJECTIVE:To evaluate the role of blood pressure as mediator of the effect of conscious sedation (CS) compared to local anesthesia (LA) on functional outcome after EVT. METHODS:Patients treated in MR CLEAN Registry centers with CS or LA as preferred anesthetic approach during EVT for ischemic stroke were analyzed. First, we evaluated the effect of CS on area under the threshold (AUT), relative difference between baseline and lowest procedural mean arterial pressure (∆LMAP) and procedural blood pressure trend, compared to LA. Second, we assessed the association between blood pressure and functional outcome (modified Rankin Scale, mRS) with multivariable regression. Lastly, we evaluated whether blood pressure explained the effect of CS on mRS. RESULTS:In 440 patients with available blood pressure data, patients treated under CS (n = 262) had larger AUTs (median 228 vs 23 mm Hg*min), larger ∆LMAP (median 16% vs 6%) and a more negative blood pressure trend (-0.22 vs -0.08 mm Hg/min) compared to LA (n = 178). Larger ∆LMAP and AUTs were associated with worse mRS (adjusted common OR (acOR) per 10%-drop 0.87, 95%CI 0.78-0.97, and acOR per 300 mm Hg*min 0.89, 95%CI 0.82-0.97). Patients treated under CS had worse mRS compared to LA (acOR 0.59, 95%CI 0.40-0.87) and this association remained when adjusting for ∆LMAP and AUT (acOR 0.62, 95%CI0.42-0.92). CONCLUSIONS:Large blood pressure drops are associated with worse functional outcome. However, blood pressure drops do not explain the worse outcomes in the CS group.