Highlights
- •Increase SUA levels preceded the development of hypertension.
- •The unidirectional relationships from SUA to SBP and DBP were significantly stronger in subjects with incident CVD.
- •the total association between SUA and subsequent risk of CVD and its subtypes were partially mediated through SBP and DBP.
- •Interventions on hyperuricemia are needed to reduce the burden of hypertension and CVD.
Abstract
Background
Although hyperuricemia and hypertension are significantly correlated, their temporal
relationship and whether this relationship is associated with risk of cardiovascular
disease (CVD) are largely unknown. This study aimed to examine temporal relationship
between hyperuricemia and hypertension, and its association with future risk of CVD.
Methods
This study included 60,285 participants from the Kailuan study. Measurement of serum
uric acid (SUA), systolic and diastolic blood pressure (SBP and DBP) were obtained
twice at 2006 (baseline) and 2010. Cross-lagged and mediation analysis were used to
examine the temporal relationship between hyperuricemia and hypertension, and the
association of this temporal relationship with CVD events risk after 2010.
Results
After adjusting for covariates, the cross-lagged path coefficients (β1) from baseline SUA to follow-up SBP and DBP were significantly greatly than path
coefficients (β2) from baseline SBP and DBP to follow-up SUA (β1=0.041 versus β2=0.003; Pdifference<0.0001 for SBP; β1=0.040 versus β2=0.000; Pdifference<0.0001 for DBP). The path coefficients from baseline SUA to follow-up SBP and DBP
in group with incident CVD were significantly greatly than that in group without incident
CVD (Pdifference of β1 in the two groups was 0.0018 for SBP and 0.0340 for DBP). Furthermore, SBP and DBP
partially mediated the effect of SUA on incident CVD, the mediation effect was 57.64%
for SBP and 46.27% for DBP. Similar mediated results were observed for stroke and
myocardial infarction.
Conclusion
Increased SUA levels probably precede elevated BP, and BP partially mediates the pathway
from SUA to incident CVD.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Internal MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- China cardiovascular diseases report 2015: a summary.J Geriatr Cardiol. 2017; 14: 1-10
- Impact of serum uric acid on incident hypertension in a worksite population of Japanese men.J. Hypertens. 2018; 36: 1499-1505
- Uric acid is a strong risk marker for developing hypertension from prehypertension: a 5-year Japanese Cohort Study.Hypertension. 2018; 71: 78-86
- Serum uric acid as a predictor of future hypertension: stratified analysis based on body mass index and age.Prev Med. 2016; 90: 201-206
- Association of hypertension and hypertriglyceridemia on incident hyperuricemia: an 8-year prospective cohort study.J Transl Med. 2020; 18: 409
- Risk factors for the incidence of hyperuricaemia: a 6-year longitudinal study of middle-aged Japanese men.Int J Epidemiol. 1999; 28: 888-893
- Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease?.Hypertension. 2003; 41: 1183-1190
- Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism.Am J Physiol Renal Physiol. 2002; 282: F991-F997
- Association between uric acid and brachial-ankle pulse wave velocity: secondary analysis of data from a cross-sectional study.Sci Rep. 2020; 10: 2282
- Temporal relationship between elevated blood pressure and arterial stiffening among middle-aged black and white adults: the Bogalusa Heart Study.Am J Epidemiol. 2016; 183: 599-608
- Changes in triglycerides and high-density lipoprotein cholesterol may precede peripheral insulin resistance, with 2-h insulin partially mediating this unidirectional relationship: a prospective cohort study.Cardiovasc Diabetol. 2016; 15: 154
- Temporal relationship between hyperuricemia and insulin resistance and its impact on future risk of hypertension.Hypertension. 2017; 70: 703-711
- Temporal relationship between hyperuricemia and obesity, and its association with future risk of type 2 diabetes.Int J Obes (Lond). 2018; 42: 1336-1344
- Longitudinal change in fasting blood glucose and myocardial infarction risk in a population without diabetes.Diabet Care. 2017; 40: 1565-1572
- Association of trajectory of cardiovascular health score and incident cardiovascular disease.JAMA Netw Open. 2019; 2e194758
- A prospective study of waist circumference trajectories and incident cardiovascular disease in China: the Kailuan Cohort Study.Am J Clin Nutr. 2021; 113: 338-347
- Hyperuricemia and risk of cardiovascular outcomes: the experience of the URRAH (Uric Acid Right for Heart Health) project.High Blood Press Cardiovasc Prev. 2020; 27: 121-128
- Identification of the uric acid thresholds predicting an increased total and cardiovascular mortality over 20 years.Hypertension. 2020; 75: 302-308
- Blood pressure trajectories and the risk of intracerebral hemorrhage and cerebral infarction: a prospective study.Hypertension. 2017; 70: 508-514
- Arterial stiffness preceding diabetes: a longitudinal study.Circ Res. 2020; 127: 1491-1498
- Recommendations on stroke prevention, diagnosis, and therapy. Report of the WHO task force on stroke and other cerebrovascular disorders.Stroke. 1989; 20: 1407-1431
- Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents.Circulation. 1994; 90: 583-612
- A new equation to estimate glomerular filtration rate.Ann Intern Med. 2009; 150: 604-612
- Temporal relationship between childhood body mass index and insulin and its impact on adult hypertension: the Bogalusa Heart Study.Hypertension. 2016; 68: 818-823
- Causal mediation analysis with survival data.Epidemiology. 2011; 22: 582-585
- Applied mediation analyses: a review and tutorial.Epidemiol Health. 2017; 39e2017035
- Mediation Analysis: a Practitioner's Guide.Annu Rev Public Health. 2016; 37: 17-32
- SAS macro for causal mediation analysis with survival data.Epidemiology. 2015; 26: e23-e24
- Uric acid relationships with lipid profile and adiposity indices: impact of different hyperuricemic thresholds.J Clin Hypertens (Greenwich). 2023; 25: 78-85
- Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study.J Hypertens. 2021; 39: 333-340
- Uric acid and risk of cardiovascular disease: a question of start and finish.Hypertension. 2021; 78: 1219-1221
- Microalbuminuria mediates the association between serum uric acid and elevation of blood pressure: a longitudinal analysis in the Gusu cohort.J Hypertens. 2020; 38: 625-632
- Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia.Am J Physiol Renal Physiol. 2008; 295: F1134-F1141
- Hyperuricemia induces endothelial dysfunction.Kidney Int. 2005; 67: 1739-1742
- Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression.J Biol Chem. 1991; 266: 8604-8608
- Pharmacologic inducers of the uric acid exporter ABCG2 as potential drugs for treatment of gouty arthritis.Asian J Pharm Sci. 2020; 15: 173-180
- Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9.Nat Commun. 2014; 5: 4642
- Recent advances on uric acid transporters.Oncotarget. 2017; 8: 100852-100862
- Genotype-based changes in serum uric acid affect blood pressure.Kidney Int. 2012; 81: 502-507
- Gout.Lancet. 2010; 375: 318-328
- Increased overall heart rate irregularity risk by hyperuricemia in the general population: results from the Korean National Health and Nutrition Examination Survey.Medicina (Kaunas). 2020; 56
- Ten-year incidence of elevated blood pressure and its predictors: the CARDIA study. Coronary Artery Risk Development in (Young) Adults.J Hum Hypertens. 1999; 13: 13-21
- Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease.Semin Nephrol. 2005; 25: 39-42
- Uric acid promotes vascular stiffness, maladaptive inflammatory responses and proteinuria in western diet fed mice.Metabolism. 2017; 74: 32-40
- Severity of hypertension mediates the association of hyperuricemia with stroke in the REGARDS case cohort study.Hypertension. 2020; 75: 246-256
- Associations between changes in serum uric acid and the risk of myocardial infarction.Int J Cardiol. 2020;
- A randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function.Clin J Am Soc Nephrol. 2011; 6: 1887-1894
Article info
Publication history
Published online: March 06, 2023
Accepted:
February 28,
2023
Received in revised form:
February 21,
2023
Received:
January 8,
2023
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
