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These findings indicate that as the number of cardiovascular risk factors increases, so does the severity of asymptomatic coronary and aortic atherosclerosis in young people.

Background Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (M pro ) inhibitor with potent pan–human-coronavirus activity in vitro. Methods We conducted a phase 2–3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19–related hospitalization or death from any cause through day 28, viral load, and safety were evaluated. Results A total of 2246 patients underwent randomization; 1120 patients received nirmatrelvir plus ritonavir (nirmatrelvir group) and 1126 received placebo (placebo group). In the planned interim analysis of patients treated within 3 days after symptom onset (modified intention-to treat population, comprising 774 of the 1361 patients in the full analysis population), the incidence of Covid-19–related hospitalization or death by day 28 was lower in the nirmatrelvir group than in the placebo group by 6.32 percentage points (95% confidence interval [CI], −9.04 to −3.59; P<0.001; relative risk reduction, 89.1%); the incidence was 0.77% (3 of 389 patients) in the nirmatrelvir group, with 0 deaths, as compared with 7.01% (27 of 385 patients) in the placebo group, with 7 deaths. Efficacy was maintained in the final analysis involving the 1379 patients in the modified intention-to-treat population, with a difference of −5.81 percentage points (95% CI, −7.78 to −3.84; P<0.001; relative risk reduction, 88.9%). All 13 deaths occurred in the placebo group. The viral load was lower with nirmaltrelvir plus ritonavir than with placebo at day 5 of treatment, with an adjusted mean difference of −0.868 log 10 copies per milliliter when treatment was initiated within 3 days after the onset of symptoms. The incidence of adverse events that emerged during the treatment period was similar in the two groups (any adverse event, 22.6% with nirmatrelvir plus ritonavir vs. 23.9% with placebo; serious adverse events, 1.6% vs. 6.6%; and adverse events leading to discontinuation of the drugs or placebo, 2.1% vs. 4.2%). Dysgeusia (5.6% vs. 0.3%) and diarrhea (3.1% vs. 1.6%) occurred more frequently with nirmatrelvir plus ritonavir than with placebo. Conclusions Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns. (Supported by Pfizer; ClinicalTrials.gov number, NCT04960202 .)

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It is well known that blood pressure (BP) levels persist over time. The present investigation examines tracking of elevated BP from childhood to adulthood and its progression to essential hypertension. In a community study of early natural history of arteriosclerosis and essential hypertension, a longitudinal cohort was constructed from two cross-sectional surveys > 15 years apart: 1505 individuals (56% female subjects, 35% black), aged 5 to 14 years at initial study. Persistence of BP was shown by significant correlations between childhood and adulthood levels (r = 0.36 to 0.50 for systolic BP and r = 0.20 to 0.42 for diastolic BP), varying by race, sex, and age. These correlations remained the same after controlling for body mass index (BMI). Twice the expected number of subjects (40% for systolic BP and 37% for diastolic BP), whose levels were in the highest quintile at childhood, remained there 15 years later. Furthermore, of the childhood characteristics, baseline BP level was most predictive of the follow-up level, followed by change in BMI. Subsequently, even at ages 20 to 31 years, prevalence of clinically diagnosed hypertension was much higher in subjects whose childhood BP was in the top quintile: 3.6 times (18% v 5%) as high in systolic BP and 2.6 times (15% v 5.8%) as high in diastolic BP, compared to subjects in every other quintile. Of the 116 subjects who developed hypertension, 48% and 41% had elevated childhood systolic and diastolic BP, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)