Cardiovascular risk escalation with caloric excess: a prospective demonstration of the mechanics in healthy adults

CONTEXT: The link between weight gain and cardiovascular risk characterized with circadian blood pressure variability [CBPV] and endothelial function [EF] is unexplored. OBJECTIVE: To prospectively demonstrate weight gain in healthy adults, increases body fat [BF], enlarges waist circumference [WC], expands visceral adipose tissue [VAT], exacerbates systemic inflammation [sIF], worsens insulin resistance [IR] and enhances functional cardiovascular disease [CVD] risk. DESIGN, SETTING AND PARTICIPANTS: Healthy men [n=11] and women [n=3] provided initial and eight-week post-caloric excess anthropometric and fasting laboratory measures. Functional CVD risk assessments: CBPV and resting EF were also obtained with 7-day automatic ambulatory BP monitoring and increased test finger peripheral arterial tone [PAT] relative to control [reported as relative hyperemia index (RHI)], respectively. INTERVENTION: After determining individualized mean energy requirements for weight maintenance over 7-days, each participant received a personalized over feeding prescription (1.4 times; 41% carbohydrate, 44% fat, and 15% protein) for 8-weeks. RESULTS: mean (SEM). Participants increased body weight [BW; +7.4(0.1) kg]*, body mass index [BMI; +2.5(0.2) kg/m(2)]*, BF [+2.0(0.01)%]*, WC [+8.2(1.0) cm]*, and VAT [+0.2(0.03) L]* and intrahepatic lipid [IHL + 0.0004(0.002) L] :*all p < 0.01. Increased subcutaneous adipose cell size [+0.3(0.01) ρL; p = 0.02] accompanied significant sIF [hs-CRP + 0.4(0.09) mg/dL; p = 0.04; leptin 6.63 ng/ml; p = 0.0008] and IR [fasting plasma glucose; [FPG] +7.0(0.6) mg/dL;p = 0.01, fasting insulin; [FI] +5.7(1.4) uIU/ml; p = 0.001, HOMA-IR +1.6(0.5); p = 0.02]. Abn CBPV {systolic [+5.4(0.8); p = 0.002, diastolic [+1.7(0.1); p = 0.07 and pulse pressure [PP] [+3.5(0.4); p = 0.003 mm Hg} or elevated heart rate [HR] [+4.9(0.5) bpm; p = 0.003] ensued. Resting RHI declined by 0.47(0.004) from initial 2.24(0.09) to 1.77(0.1); p = 0.001, indicating endothelial dysfunction [ED]. CONCLUSIONS: Controlled caloric excess in healthy human adults over only 8-weeks significantly increased BF, VAT, sIF [hs-CRP], IR [FPG, FI, HOMA-IR] and functional CVD risk [measured as abnormal circadian blood pressure variability and impaired resting endothelial function].