Kidney Function Decline in Young Adulthood and Subsequent 24-Hour Ambulatory Blood Pressure in Midlife: The CARDIA Study

Hypertension (HTN) and chronic kidney disease (CKD) are comorbid conditions. A decline in kidney function is associated with an increase in blood pressure (BP), and a sustained elevation in BP leads to the progression of kidney function decline.1Bakris G.L. Williams M. Dworkin L. et al.Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group.Am J Kidney Dis. 2000; 36: 646-661Abstract Full Text Full Text PDF PubMed Scopus (1217) Google Scholar As CKD stage advances, the prevalence of HTN increases, and BP becomes more difficult to control.2Muntner P. Anderson A. Charleston J. et al.Hypertension awareness, treatment, and control in adults with CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study.Am J Kidney Dis. 2010; 55: 441-451Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar Previous studies have focused on the associations between HTN and longitudinal changes in the estimated glomerular filtration rate (eGFR). Patients with HTN or with higher baseline office BP were found to have faster rates of eGFR decline on follow-up in population studies.3Judson G.L. Rubinsky A.D. Shlipak M.G. et al.Longitudinal blood pressure changes and kidney function decline in persons without chronic kidney disease: findings from the MESA study.Am J Hypertens. 2018; 31: 600-608Crossref PubMed Scopus (8) Google Scholar,4Yu Z. Rebholz C.M. Wong E. et al.Association between hypertension and kidney function decline: the Atherosclerosis Risk in Communities (ARIC) Study.Am J Kidney Dis. 2019; 74: 310-319Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Outside the office setting, ambulatory BP monitoring (ABPM) is the reference standard to measure the BP. ABPM provides data on the average BP over 24 hours and can identify several BP profiles by comparing the office and out-of-office BP readings.5Muntner P. Shimbo D. Carey R.M. et al.Measurement of blood pressure in humans: a scientific statement from the American Heart Association.Hypertension. 2019; 73: e35-e66Crossref PubMed Scopus (361) Google Scholar Characterizing BP profiles such as masked HTN (nonhypertensive inside of the office but hypertensive outside of the office) or sustained HTN (hypertensive inside and outside of the office) among patients with and without CKD may help identify the risk of target organ damage and adverse clinical outcomes.5Muntner P. Shimbo D. Carey R.M. et al.Measurement of blood pressure in humans: a scientific statement from the American Heart Association.Hypertension. 2019; 73: e35-e66Crossref PubMed Scopus (361) Google Scholar Conversely, incident CKD and more rapid declines in eGFR may be a risk factor for masked or sustained HTN. Although cross-sectional studies have shown an association between masked HTN and reduced eGFR, no study has evaluated the association between eGFR decline and incident CKD as a predictor of BP profiles assessed using ABPM.6Sega R. Trocino G. Lanzarotti A. et al.Alterations of cardiac structure in patients with isolated office, ambulatory, or home hypertension: data from the general population (Pressione Arteriose Monitorate E Loro Associazioni [PAMELA] Study).Circulation. 2001; 104: 1385-1392Crossref PubMed Scopus (446) Google Scholar,7Mojón A. Ayala D.E. Piñeiro L. et al.Comparison of ambulatory blood pressure parameters of hypertensive patients with and without chronic kidney disease.Chronobiol Int. 2013; 30: 145-158Crossref PubMed Scopus (109) Google Scholar Therefore, the purpose of this cross-sectional study was to examine the association of the development of CKD with subsequent BP on ABPM. We conducted post hoc analyses of data from CARDIA (Coronary Artery Risk Development in Young Adults), a prospective cohort study conducted in the United States to understand risk factors for the development of cardiovascular disease.8Friedman G.D. Cutter G.R. Donahue R.P. et al.CARDIA: study design, recruitment, and some characteristics of the examined subjects.J Clin Epidemiol. 1988; 41: 1105-1116Abstract Full Text PDF PubMed Scopus (1145) Google Scholar Age, race, and sex were self-reported at baseline and were confirmed at the year 2 examination. The remaining clinical data were obtained at the year 30 examination. Serum creatinine, urine albumin, and creatinine samples from year 10, 15, 20, 25, and 30 examinations were collected. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was used to calculate the eGFR (mL/min/1.73m2), and albuminuria was defined as having a urinary albumin-to-creatinine ratio of >30 mg/g.9Levey A.S. Stevens L.A. Schmid C.H. et al.A new equation to estimate glomerular filtration rate.Ann Intern Med. 2009; 150: 604-612Crossref PubMed Scopus (14386) Google Scholar We defined the development of CKD as having an eGFR of <60 mL/min/1.73m2 or albuminuria at any time point between year 10 and 30. The office BP was measured by a certified staff following a standardized protocol. A validated monitor and appropriate cuff size (Item S1) was used for the 24-hour ABPM at the year 30 visit. We calculated the mean 24-hour, mean awake, and mean nocturnal BP, ABPM phenotypes (masked HTN [BP: office, <140/90 mm Hg; 24 h, ≥130/80 mm Hg], sustained normotension [BP: office, <140/90 mm Hg; 24 h, <130/80 mm Hg), and dipping patterns (dippers vs nondippers: reduction in the mean BP from day to night of 10%–20% vs <10%).10Pickering T.G. Hall J.E. Appel L.J. et al.Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research.Circulation. 2005; 111: 697-716Crossref PubMed Scopus (1649) Google Scholar For the present analysis, we included participants who had a valid ABPM.11Thijs L. Hansen T.W. Kikuya M. et al.The International Database of Ambulatory Blood Pressure in relation to Cardiovascular Outcome (IDACO): protocol and research perspectives.Blood Press Monit. 2007; 12: 255-262Crossref PubMed Scopus (105) Google Scholar,12Octavio J.A. Contreras J. Amair P. et al.Time-weighted vs. conventional quantification of 24-h average systolic and diastolic ambulatory blood pressures.J Hypertens. 2010; 28: 459-464Crossref PubMed Scopus (30) Google Scholar We used linear and logistic regression to evaluate the association between the development of CKD and systolic BP on ABPM, masked HTN (vs sustained normotension), and nondipping systolic BP. We adjusted for demographic and clinical characteristics. All analyses were stratified by whether participants were on antihypertensive medications at year 30, as we hypothesized that the prevalence of ABPM phenotypes would be higher for participants taking antihypertensives. The sensitivity analysis included using the CKD-EPI 2021 equation (without race) and using diastolic BP to define ABPM phenotypes.13Inker L.A. Eneanya N.D. Coresh J. et al.New creatinine- and cystatin C-based equations to estimate GFR without race.N Engl J Med. 2021; 385: 1737-1749Crossref PubMed Scopus (96) Google Scholar,14Delgado C. Baweja M. Crews D.C. et al.A unifying approach for GFR estimation: recommendations of the NKF-ASN Task Force on reassessing the inclusion of race in diagnosing kidney disease.Am J Kidney Dis. 2021; S0272-6386 (00828-3)Google Scholar We included 763 participants with complete ABPM (Item S1). The participants who were not on antihypertensive medications (450 [59%]) had a mean age of 54.6 ± 3.7 years; 256 (57%) were women; 226 (50%) were African American; eGFR (year 30) was 90.8 ± 15.4 mL/min/1.73m2; and 62 (14%) had CKD. The participants who were on antihypertensive medication (313 [41%]) had a mean age of 55.0 ± 3.7 years; 201 (64%) were women; 68 (22%) were African American; eGFR (year 30) was 90.4 ± 20.1 mL/min/1.73m2; and 103 (33%) had CKD. Among all adults (receiving and not receiving antihypertensive medications), the development of CKD was not associated with the mean 24-hour systolic and diastolic BP or the mean awake systolic and diastolic BP after adjusting for demographic and clinical characteristics (Table 1; Item S1). However, among those not receiving antihypertensives, CKD was associated with higher nocturnal systolic BP (β [95% CI]: 3.6 [0.40-6.79]) and nocturnal diastolic BP (β [95% CI]: 2.8 [0.84-4.77]) (Table 1; Item S1). We found no association between masked HTN or nondipping BP and the development of CKD in the fully adjusted models (Table 2; Item S1) These findings were consistent even when defining CKD using the CKD-EPI 2021 equation.Table 1Association of CKD Development (Compared With Normal Kidney Function Between Years 10 and 30) With Systolic Ambulatory BP of Participants (at year 30) On and Not On Antihypertensive Medications1Bakris G.L. Williams M. Dworkin L. et al.Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group.Am J Kidney Dis. 2000; 36: 646-661Abstract Full Text Full Text PDF PubMed Scopus (1217) Google Scholarβ (95% CI)Model 1Model 2Model 3Participants Not On Antihypertensive Medications (n=450)24-Hour systolic BP4.43 (0.72 to 8.14)aStatistically significant.3.26 (−0.50 to 7.01)1.65 (−1.05 to 4.36)Awake systolic BP3.39 (−0.52 to 7.29)2.41 (−1.60 to 6.41)0.71 (−2.17 to 3.59)Nocturnal systolic BP6.47 (2.67 to 10.26)aStatistically significant.5.05 (1.23 to 8.87)aStatistically significant.3.59 (0.40 to 6.79)aStatistically significant.Participants On Antihypertensive Medications (n=313)24-Hour systolic BP2.08 (−1.34 to 5.49)0.80 (−2.69 to 4.29)0.27 (−2.60 to 3.13)Awake systolic BP1.41 (−2.17 to 4.98)0.24 (−3.39 to 3.87)−0.35 (−3.31 to 2.61)Nocturnal systolic BP3.50 (−0.17 to 7.17)1.81 (−1.97 to 5.59)1.18 (−2.22 to 4.59)Note: Model 1: unadjusted; model 2: adjusted for study center, age, sex, race, and educational attainment; model 3: model 2 + smoking status, history of diabetes, history of hypertension, family history of hypertension, statin use at year 30, body mass index at year 30, total cholesterol at year 30, office systolic at year 30, office diastolic at year 30, and estimated glomerular filtration rate at year 30.Abbreviations: BP, blood pressure; CKD, chronic kidney disease.a Statistically significant. Open table in a new tab Table 2Association of CKD Development (Compared With Normal Kidney Function Between Years 10 and 30) With Ambulatory BP Phenotypes (at Year 30) Based on The 2005 ACC/AHA Guidelines of Participants On and Not On Antihypertensive MedicationsOR (95% CI)Model 1Model 2Model 3Masked Hypertension vs Sustained NormotensionParticipants Not On Antihypertensive Medications (n=450)Using office BP and 24 hour ambulatory BP1.70 (0.94-3.04)1.62 (0.84-3.08)1.72 (0.60-4.84)Using office BP and awake ambulatory BP1.48 (0.82-2.63)1.34 (0.70-2.53)1.26 (0.46-3.37)Using office BP and nocturnal ambulatory BP1.89 (1.04-3.36)aStatistically significant.1.61 (0.84-3.08)2.03 (0.78-5.21)Participants On Antihypertensive Medications (n=313)Using office BP and 24 hour ambulatory BP1.29 (0.76-2.21)0.92 (0.49-1.66)0.57 (0.24-1.33)Using office BP and awake ambulatory BP1.09 (0.63-1.86)0.86 (0.47-1.55)0.65 (0.28-1.49)Using office BP and nocturnal ambulatory BP1.54 (0.91-2.62)1.16 (0.65-2.06)0.94 (0.43-2.02)Note: Model 1: unadjusted; model 2: adjusted for study center, age, sex, race, and educational attainment; model 3: model 2 + smoking status, history of diabetes, history of hypertension, family history of hypertension, statin use at year 30, body mass index at year 30, total cholesterol at year 30, office systolic at year 30, office diastolic at year 30, and estimated glomerular filtration rate at year 30. The white coat effect and sustained hypertension (Item S1) were prevalent among 8 (2%) and 33 (7%) participants not on antihypertensive medications and among 7 (2%) and 46 (15%) participants on antihypertensive medications, respectively. Because of the limited sample size, we were unable to study the association between these BP phenotypes and incident CKD.Abbreviations: BP, blood pressure; CKD, chronic kidney disease; OR, odds ratio.a Statistically significant. Open table in a new tab Note: Model 1: unadjusted; model 2: adjusted for study center, age, sex, race, and educational attainment; model 3: model 2 + smoking status, history of diabetes, history of hypertension, family history of hypertension, statin use at year 30, body mass index at year 30, total cholesterol at year 30, office systolic at year 30, office diastolic at year 30, and estimated glomerular filtration rate at year 30. Abbreviations: BP, blood pressure; CKD, chronic kidney disease. Note: Model 1: unadjusted; model 2: adjusted for study center, age, sex, race, and educational attainment; model 3: model 2 + smoking status, history of diabetes, history of hypertension, family history of hypertension, statin use at year 30, body mass index at year 30, total cholesterol at year 30, office systolic at year 30, office diastolic at year 30, and estimated glomerular filtration rate at year 30. The white coat effect and sustained hypertension (Item S1) were prevalent among 8 (2%) and 33 (7%) participants not on antihypertensive medications and among 7 (2%) and 46 (15%) participants on antihypertensive medications, respectively. Because of the limited sample size, we were unable to study the association between these BP phenotypes and incident CKD. Abbreviations: BP, blood pressure; CKD, chronic kidney disease; OR, odds ratio. We found that overall worsening kidney function was associated with higher nocturnal systolic and diastolic BP among adults not receiving antihypertensive medications, but this association was attenuated by demographic factors and comorbid conditions. These results are on par with the findings of the study by Mojón et al,7Mojón A. Ayala D.E. Piñeiro L. et al.Comparison of ambulatory blood pressure parameters of hypertensive patients with and without chronic kidney disease.Chronobiol Int. 2013; 30: 145-158Crossref PubMed Scopus (109) Google Scholar who showed that the development of CKD was associated with higher nocturnal systolic BP. Our data suggest that the incidence of CKD during young adulthood was not associated with masked HTN and nondipping or higher awake or 24-hour BP in midlife among individuals with mostly normal eGFR. The main limitation of this study include the modest sample size of patients enrolled in the CARDIA study with complete ABPM at year 30 and the cross-sectional nature of this analysis. These findings show that compared with patients without CKD, those with CKD have higher nocturnal BP, particularly if they are not using any antihypertensive medication. Whether noctural BP might be a precursor for CKD should be explored further. Research idea and study design: LG, DS, DRJ, HK, JBC, PM, YY, PED; Data acquisition: LG, DRJ, PM, PD; Data analysis and interpretation: LG, DS, DRJ, HK, JBC, PM, YY, PED; Statistical analysis: LG, DRJ, PED. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201800003I, HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, and HHSN268201800007I from the National Heart, Lung, and Blood Institute (NHLBI). Dr Drawz receives support through R01 HL136679 from the NHLBI; Dr Shimbo and Dr Muntner receive research support from the NHLBI through R01HL139716 and R01HL117323. Dr Shimbo receives support through K24-HL125704 from the NHLBI. Dr Cohen was supported by K23HL133843 and R01-HL153646 from the NHLBI. Dr Yano and Dr Muntner are supported by the NHLBI through R01HL144773. Dr Ghazi is supported by the American Heart Association postdoctoral fellowship. None of the funders had any role in the study design, data collection, analysis, reporting, or decision to submit the application. The authors declare that they have no relevant financial interests. Received July 15, 2021. Evaluated by 3 external peer reviewers with direct editorial input from the Editor-in-Chief. Accepted in revised form October 24, 2021. Download .pdf (.22 MB) Help with pdf files Supplementary File (PDF)