The 2017 American College of Cardiology/American Heart Association high blood pressure (BP) guidelines recommend risk assessment of atherosclerotic cardiovascular disease to inform hypertension treatment in adults with elevated BP or low-risk stage I hypertension. The use of coronary artery calcium (CAC) score to guide hypertension therapy has not been adequately evaluated. Participants free of cardiovascular disease were pooled from Multi-Ethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Jackson Heart Study. The risk for incident cardiovascular events (heart failure, stroke, coronary heart disease), by CAC status (CAC-0 or CAC>0) and BP treatment group was assessed using multivariable-adjusted Cox regression. The 10-year number needed to treat to prevent a single cardiovascular event was also estimated. This study included 6461 participants (median age 53 years; 53.3% women; 32.3% Black participants). Over a median follow-up of 8.5 years, 347 incident cardiovascular events occurred. Compared with those with normal BP, the risk of incident cardiovascular event was higher among those with elevated BP/low-risk stage I hypertension and CAC>0 (hazard ratio, 2.4 [95% CI, 1.7–3.4]) and high-risk stage I/stage II hypertension (BP, 140–160/80–100 mm Hg) with CAC>0 (hazard ratio, 2.9 [95% CI, 2.1–4.0]). A similar pattern was evident across racial subgroups and for individual study outcomes. Among those with CAC-0, the 10-year number needed to treat was 160 for elevated BP/low-risk stage I hypertension and 44 for high-risk stage I or stage II hypertension (BP, 140–160/80–100 mm Hg). Among those with CAC>0, the 10-year number needed to treat was 36 and 22, respectively. Utilization of the CAC score may guide the initiation of hypertension therapy and preventive approaches to personalize cardiovascular risk reduction among individuals where the current guidelines do not recommend treatment.

Kidney donation reduces renal function by ≈30% allowing study of the cardiovascular effects of a reduced estimated glomerular filtration rate without comorbidities. We report 5-year results of a longitudinal, parallel-group, blinded end-point study of living kidney donors (n=50) and healthy controls (n=45). The primary end point, left ventricular mass, was measured using cardiac magnetic resonance. Secondary end points, 24-hour ambulatory blood pressure, and pulse wave velocity were measured using validated blood pressure monitors and the SphygmoCor device. Effect sizes were calculated as differences between change from baseline in the donor and control groups. In donors, estimated glomerular filtration rate was 95±15 mL/min per 1.73 m2 at baseline (predonation) and 67±14 mL/min per 1.73 m2 at 5 years. In controls, there was a −1±2 mL/min per 1.73 m2 decline per annum. Change in left ventricular mass at 5 years was not significantly different between donors and controls (mean difference, +0.40 g [95% CI, −4.68 to 5.49] P=0.876), despite an initial increase in mass in donors compared with controls at 12 months. Pulse wave velocity, which increased in donors at 12 months, returned to levels not different from controls at 5 years (mean difference, −0.24 m/s [95% CI, −0.69 to 0.21]). Change in ambulatory systolic blood pressure was not different in donors compared with controls (mean difference, +1.91 mm Hg [95% CI, −2.72 to 6.54]). We found no evidence that the reduction in estimated glomerular filtration rate after kidney donation was associated with a change in left ventricular mass detectable by magnetic resonance imaging at 5 years.

After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations. We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs). Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020. We excluded patients with a history of diabetes, known cardiovascular disease, chronic renal failure, or chronic respiratory disease during the previous 5 years, to only consider patients treated for uncomplicated hypertension and to limit indication bias. The primary end point was time to hospitalization for COVID-19. The secondary end point was time to intubation/death during a hospital stay for COVID-19. In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19. ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65–0.83] and 0.84 [0.76–0.93], respectively) and a lower risk of intubation/death. Risks were slightly lower for ACE inhibitor users than for ARB users. This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs. These results, if confirmed, tend to contradict previous hypotheses and raise new hypotheses.

Exposure to traffic-related air pollution (TRAP) may contribute to increased prevalence of hypertension and elevated blood pressure (BP) for residents of near-highway neighborhoods. Relatively few studies have investigated the effects of reducing TRAP exposure on short-term changes in BP. We assessed whether reducing indoor TRAP concentrations by using stand-alone high-efficiency particulate arrestance (HEPA) filters and limiting infiltration through doors and windows effectively prevented acute (ie, over a span of hours) increases in BP. Using a 3-period crossover design, 77 participants were randomized to attend three 2-hour-long exposure sessions separated by 1-week washout periods. Each participant was exposed to high, medium, and low TRAP concentrations in a room near an interstate highway. Particle number concentrations, black carbon concentrations, and temperature were monitored continuously. Systolic BP (SBP), diastolic BP, and heart rate were measured every 10 minutes. Outcomes were analyzed with a linear mixed model. The primary outcome was the change in SBP from 20 minutes from the start of exposure. SBP increased with exposure duration, and the amount of increase was related to the magnitude of exposure. The mean change in SBP was 0.6 mm Hg for low exposure (mean particle number and black carbon concentrations, 2500 particles/cm³ and 149 ng/m³), 1.3 mm Hg for medium exposure (mean particle number and black carbon concentrations, 11 000 particles/cm³ and 409 ng/m³), and 2.8 mm Hg for high exposure (mean particle number and black carbon concentrations, 30 000 particles/cm³ and 826 ng/m³; linear trend P=0.019). There were no statistically significant differences in the secondary outcomes, diastolic BP, or heart rate. In conclusion, reducing indoor concentrations of TRAP was effective in preventing acute increases in SBP.

The association of blood pressure (BP) and hypertension with the presence of different types of brain lesions in patients with atrial fibrillation is unclear. BP values were obtained in a multicenter cohort of patients with atrial fibrillation. Systolic and diastolic BP was categorized in predefined groups. All patients underwent brain magnetic resonance imaging and neurocognitive testing. Brain lesions were classified as large noncortical or cortical infarcts, small noncortical infarcts, microbleeds, or white matter lesions. White matter lesions were graded according to the Fazekas scale. Overall, 1738 patients with atrial fibrillation were enrolled in this cross-sectional analysis (mean age, 73 years, 73% males). Mean BP was 135/79 mm Hg, and 67% of participants were taking BP-lowering treatment. White matter lesions Fazekas ≥2 were found in 54%, large noncortical or cortical infarcts in 22%, small noncortical infarcts in 21%, and microbleeds in 22% of patients, respectively. Compared with patients with systolic BP <120 mm Hg, the adjusted odds ratios (95% CI) for Fazekas≥2 was 1.25 (0.94–1.66), 1.41 (1.03–1.93), and 2.54 (1.65–3.95) among patients with systolic BP of 120 to 140, 140 to 160, and ≥160 mm Hg (P for linear trend<0.001). Per 5 mm Hg increase in systolic and diastolic BP, the adjusted β-coefficient (95% CI) for log-transformed white matter lesions was 0.04 (0.02–0.05), P<0.001 and 0.04 (0.01–0.06), P=0.004. Systolic BP was associated with small noncortical infarcts (odds ratios [95% CI] per 5 mm Hg 1.05 [1.01–1.08], P=0.006), microbleeds were associated with hypertension, but large noncortical or cortical infarcts were not associated with BP or hypertension. After multivariable adjustment, BP and hypertension were not associated with neurocognitive function. Among patients with atrial fibrillation, BP is strongly associated with the presence and extent of white matter lesions, but there is no association with large noncortical or cortical infarcts.

Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. To address this question, this study explored the relationship between genetic predictors of blood pressure and risk of AF. We secondarily explored the relationship between genetically proxied use of antihypertensive drugs and risk of AF. Two-sample Mendelian randomization was performed using an inverse-variance weighted meta-analysis with weighted median Mendelian randomization and Egger intercept tests performed as sensitivity analyses. Summary statistics for systolic blood pressure, diastolic blood pressure, and pulse pressure were obtained from the International Consortium of Blood Pressure and the UK Biobank discovery analysis and AF from the 2018 Atrial Fibrillation Genetics Consortium multiethnic genome-wide association studies. Increases in genetically proxied systolic blood pressure, diastolic blood pressure, or pulse pressure by 10 mm Hg were associated with increased odds of AF (systolic blood pressure: odds ratio [OR], 1.17 [95% CI, 1.11–1.22]; P=1×10⁻¹¹; diastolic blood pressure: OR, 1.25 [95% CI, 1.16–1.35]; P=3×10⁻⁸; pulse pressure: OR, 1.1 [95% CI, 1.0–1.2]; P=0.05). Decreases in systolic blood pressure by 10 mm Hg estimated by genetic proxies of antihypertensive medications showed calcium channel blockers (OR, 0.66 [95% CI, 0.57–0.76]; P=8×10⁻⁹) and β-blockers (OR, 0.61 [95% CI, 0.46–0.81]; P=6×10⁻⁴) decreased the risk of AF. Blood pressure–increasing genetic variants were associated with increased risk of AF, consistent with a causal relationship between blood pressure and AF. These data support the concept that blood pressure reduction with calcium channel blockade or β-blockade could reduce the risk of AF.

Compared with brachial blood pressure (BP), central systolic BP (SBP) can provide a better indication of the hemodynamic strain inflicted on target organs, but it is unclear whether this translates into improved cardiovascular risk stratification. We aimed to assess which of central or brachial BP best predicts cardiovascular risk and to identify the central SBP threshold associated with increased risk of future cardiovascular events. This study included 13 461 participants of CARTaGENE with available central BP and follow-up data from administrative databases but without cardiovascular disease or antihypertensive medication. Central BP was estimated by radial artery tonometry, calibrated for brachial SBP and diastolic BP (type I), and a generalized transfer function (SphygmoCor). The outcome was major adverse cardiovascular events. Cox proportional-hazards models, differences in areas under the curves, net reclassification indices, and integrated discrimination indices were calculated. Youden index was used to identify SBP thresholds. Over a median follow-up of 8.75 years, 1327 major adverse cardiovascular events occurred. The differences in areas under the curves, net reclassification indices, and integrated discrimination indices were of 0.2% ([95% CI, 0.1–0.3] P<0.01), 0.11 ([95% CI, 0.03–0.20] P=0.01), and 0.0004 ([95% CI, −0.0001 to 0.0014] P=0.3), all likely not clinically significant. Central and brachial SBPs of 112 mm Hg (95% CI, 111.2–114.1) and 121 mm Hg (95% CI, 120.2–121.9) were identified as optimal BP thresholds. In conclusion, central BP measured with a type I device is statistically but likely not clinically superior to brachial BP in a general population without prior cardiovascular disease. Based on the risk of major adverse cardiovascular events, the optimal type I central SBP appears to be 112 mm Hg.

Antihypertensive drug treatment is cost-effective for adults at high risk of developing cardiovascular disease (CVD). However, the cost-effectiveness in people with stage 1 hypertension (140–159 mm Hg systolic blood pressure) at lower CVD risk remains unclear. The objective was to establish the 10-year CVD risk threshold where initiating antihypertensive drug treatment for primary prevention in adults, with stage 1 hypertension, becomes cost-effective. A lifetime horizon Markov model compared antihypertensive drug versus no treatment, using a UK National Health Service perspective. Analyses were conducted for groups ranging between 5% and 20% 10-year CVD risk. Health states included no CVD event, CVD and non-CVD death, and 6 nonfatal CVD morbidities. Interventions were compared using cost-per-quality-adjusted life-years. The base-case age was 60, with analyses repeated between ages 40 and 75. The model was run separately for men and women, and threshold CVD risk assessed against the minimum plausible risk for each group. Treatment was cost-effective at 10% CVD risk for both sexes (incremental cost-effectiveness ratio £10 017/quality-adjusted life-year [$14 542] men, £8635/QALY [$12 536] women) in the base-case. The result was robust in probabilistic and deterministic sensitivity analyses but was sensitive to treatment effects. Treatment was cost-effective for men regardless of age and women aged >60. Initiating treatment in stage 1 hypertension for people aged 60 is cost-effective regardless of 10-year CVD risk. For other age groups, it is also cost-effective to treat regardless of risk, except in younger women.

Activation of PRR ([pro]renin receptor) contributes to enhancement of intrarenal RAS and renal medullary α-ENaC and thus elevated blood pressure during Ang II (angiotensin II) infusion. The goal of the present study was to test whether such action of PRR was mediated by sPRR (soluble PRR), generated by S1P (site-1 protease), a newly identified PRR cleavage protease. F1 B6129SF1/J mice were infused for 6 days with control or Ang II at 300 ng/kg per day alone or in combination with S1P inhibitor PF-429242 (PF), and blood pressure was monitored by radiotelemetry. S1P inhibition significantly attenuated Ang II–induced hypertension accompanied with suppressed urinary and renal medullary renin levels and expression of renal medullary but not renal cortical α-ENaC expression. The effects of S1P inhibition were all reversed by supplement with histidine-tagged sPRR termed as sPRR-His. Ussing chamber technique was performed to determine amiloride-sensitive short-circuit current, an index of ENaC activity in confluent mouse cortical collecting duct cell line cells exposed for 24 hours to Ang II, Ang II + PF, or Ang II + PF + sPRR-His. Ang II–induced ENaC activity was blocked by PF, which was reversed by sPRR-His. Together, these results support that S1P-derived sPRR mediates Ang II–induced hypertension through enhancement of intrarenal renin level and activation of ENaC.