Arterial Stiffness in Hypertension: an Update.
Dumor Korshie,Shoemaker-Moyle Michael,Nistala Ravi,Whaley-Connell Adam
Current hypertension reports
PURPOSE OF REVIEW:To update and review novel insights into the mechanisms, measurements, and therapeutic approaches to arterial stiffness. RECENT FINDINGS:Arterial (e.g., vascular) stiffness has been shown over time to prognosticate for cardiovascular and kidney outcomes. In this context, there has been increased interest behind the mechanisms that drive arterial stiffness beyond aging and interest in how to apply newer technologies in measurement of arterial stiffness. Pulse wave velocity has been the gold standard for measurement but industry has been innovating to improve measurement with use of single-point PWV as well as pharmacologic approaches with anti-hypertensives and oral hypoglycemic agents. Emerging data on the role of the mineralocorticoid receptor, the endothelial sodium channel (EnNaC), and uric acid in arterial stiffness are promising a number of potential therapies. Newer techniques of measuring PWV for arterial stiffness and novel therapies may soon lead to better outcomes from hypertension complications.
10.1007/s11906-018-0867-x
Association between serum uric acid and arterial stiffness in a large-aged 40-70 years old population.
Journal of clinical hypertension (Greenwich, Conn.)
Arterial stiffness (AS), measured by arterial stiffness index (ASI), is a determinant in cardiovascular (CV) diseases. A high serum uric acid (SUA) level is a known risk factor for CV disease. The authors investigated the relationship between SUA and ASI in the middle-age UK Biobank population study. AS was defined as ASI > 10 m/s. A cross-sectional study was conducted from 126 663 participants. Participants were divided into four quartiles according to SUA levels and sex. Sex multivariate analyses were performed with adjustment for confounding factors. The average ASI for overall participants was 9.3 m/s (SD: 2.9); 9.9 m/s (SD: 2.8) for men and 8.7 m/s (SD: 2.9) for women (P < .001). Men presented higher SUA rate (351.3 mmol/L (SD:67.9)) than women (270.7 mmol/L (SD:64.4)), P < .001. In men multivariate analysis, SUA remained a determinant of AS, with an increase in the strength of the association between the quartiles, Q4 versus Q1, OR = 1.10 [1.05-1.16], P < .001, Q3 versus Q1, OR = 1.09 [1.04-1.14], P < .001 but not between Q2 and Q1 (P = .136). In women, SUA remained significant for AS, with an increase in the strength of the association between the quartiles, Q4 versus Q1, OR = 1.22 [1.15-1.30], P < .001, Q3 versus Q1, OR = 1.13 [1.07-1.19], P < .001 and no difference between Q2 and Q1 (P = .101). When applying continuous SUA values in the multivariate analysis, SUA remained significant (P < .001), with a Youden index value for men = 338.3 mmol/L and for women = 267.3 mmol/L. High SUA levels were associated with AS, suggesting that SUA could be used as a predictor of atherosclerosis.
10.1111/jch.14527
Impact of Uric Acid on Hypertension Occurrence and Target Organ Damage: Insights From the STANISLAS Cohort With a 20-Year Follow-up.
Kanbay Mehmet,Girerd Nicolas,Machu Jean-Loup,Bozec Erwan,Duarte Kevin,Boivin Jean-Marc,Wagner Sandra,Ferreira João Pedro,Zannad Faiez,Rossignol Patrick
American journal of hypertension
BACKGROUND:Recent studies have shown that hyperuricemia may be associated with incident hypertension (HTN). We examined whether serum uric acid (SUA) is a predictor of HTN and target organ damage (TOD) 20 years later in initially healthy middle-aged individuals. METHODS:Participants from the Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) a single-center familial longitudinal cohort study (961 initially healthy adults and 570 children) underwent clinical and laboratory measurements at baseline and after approximately 20 years. Blood pressure (BP: using ambulatory BP measurements), urine albumin-to-creatinine ratio, estimated glomerular filtration rate (eGFR), left ventricular hypertrophy (LVH), diastolic dysfunction, and carotid-femoral pulse wave velocity (PWV) were measured at the end of follow-up. RESULTS:In the parent population, higher baseline or last SUA levels and higher change in SUA (ΔUA) were significantly associated with an increased risk of HTN development, even after adjusting for known HTN risk factors (all P < 0.01). Higher baseline SUA was marginally associated with an increased risk of having high carotid-femoral PWV (P = 0.05). The association of SUA with BP increase was body mass index dependent (the increase in BP being greater in leaner subjects; interactionp < 0.05), and the association of SUA with eGFR decline was age dependent (the decline in eGFR being greater in older subjects; interactionp < 0.05). There was no significant association between SUA and diastolic dysfunction or LVH. In the whole population (i.e. including children), a significant association between SUA at baseline and the risk of HTN and higher carotid-femoral PWV was also found (both P < 0.02). CONCLUSIONS:Increased SUA is associated with the development of HTN and vascular/renal TOD in initially healthy midlife subjects.
10.1093/ajh/hpaa030
The impact of serum acid, arterial stiffness, and hypertension as a mediating factor: A cohort study.
Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese
BACKGROUND:Serum uric acid (SUA) has been associated with arterial stiffness. However, previous studies were limited to contradicting cross-sectional studies. This study aimed to examine the longitudinal association between SUA and the progression of arterial stiffness and the potential mechanisms. METHODS:Based on the Kailuan study, arterial stiffness progression was assessed by the annual growth rate of repeatedly measured brachial-ankle pulse wave velocity (baPWV). Generalized linear regression models were used to estimate the association of SUA with baseline arterial stiffness (n = 37,659) and arterial stiffness progression (n = 16,506), and Cox regressions were used to investigate the risk of incident arterial stiffness (n = 13,843). Mediation analysis was used to explore the potential mediators of the associations. RESULTS:Per standard deviation increase in SUA was associated with an 11.89 cm/s increment (95% confidence interval [CI], 8.60-15.17) in baseline baPWV and a 2.67 cm/s/yr increment in the annual growth rate of baPWV. During the 5.77-year follow-up, there were 1953 cases of incident arterial stiffness. Participants in the highest quartile of SUA had a 39% higher risk of arterial stiffness (HR, 1.39; 95% CI, 1.21-1.60), as compared with those in the lowest quartile of SUA. Furthermore, the observed associations were more pronounced in women than in men (P<0.05). The pathological pathway from high SUA to arterial stiffness was mainly mediated through hypertension (mediated proportion: 24.74%). CONCLUSIONS:Our study indicates that SUA was positively associated with the risk of arterial stiffness and its progression, especially in women. The association was mainly mediated through hypertension.
10.1016/j.hjc.2023.07.009
Blood Haemoglobin Concentration Is Directly and Independently Related with Pulse Wave Velocity, a Measure of Large Artery Stiffness.
Journal of clinical medicine
High haemoglobin level has been associated with metabolic syndrome, elevated blood pressure (BP), and increased mortality risk. In this cross-sectional study, we investigated the association of blood haemoglobin with haemodynamics in 743 subjects, using whole-body impedance cardiography and pulse wave analysis. The participants were allocated to sex-stratified haemoglobin tertiles with mean values 135, 144, and 154 g/L, respectively. The mean age was similar in all tertiles, while body mass index was higher in the highest versus the lowest haemoglobin tertile. The highest haemoglobin tertile had the highest erythrocyte and leukocyte counts, plasma C-reactive protein, uric acid, renin activity, and aldosterone. The lipid profile was less favourable and insulin sensitivity lower in the highest versus the lowest haemoglobin tertile. Aortic BP, cardiac output, and systemic vascular resistance were similar in all tertiles, while the pulse wave velocity (PWV) was higher in the highest versus the lowest haemoglobin tertile. In linear regression analysis, age (Beta 0.478), mean aortic BP (Beta 0.178), uric acid (Beta 0.150), heart rate (Beta 0.148), and aldosterone-to-renin ratio (Beta 0.123) had the strongest associations with PWV ( < 0.001 for all). Additionally, haemoglobin concentration was an explanatory factory for PWV (Beta 0.070, = 0.028). To conclude, blood haemoglobin concentration had a small direct and independent association with a measure of large artery stiffness.
10.3390/jcm12247623
Carotid-femoral pulse wave velocity is significantly increased in newly diagnosed hypertensive patients with primary hyperparathyroidism and significantly related with serum calcium level.
Journal of ultrasound
BACKGROUND:Primary hyperparathyroidism (PHP) is a rare cause of secondary hypertension (HT), but in patients with PHP, HT is very common and 20-80% of patients have HT. The aim of this study was to evaluate the change in carotid-femoral pulse wave velocity (CF-PWV) in hypertensive patients with PHP, and was to determine the clinical, laboratory, and echocardiographic parameters associated with CF-PWV. METHODS:The study included 83 newly diagnosed hypertensive patients with PHP and 83 patients with newly diagnosed essential HT without PHP. All patients underwent echocardiography and CF-PWV measurements. RESULTS:In patients with PHP, blood urea nitrogen, hs-CRP, uric acid, serum and urine calcium, parathyroid hormone level, CF-PWV value, LV wall thickness, LVMI, aortic and left atrium (LA) diameter, and presence of LVH and CF-PWV > 10 m/s were higher, and serum phosphorus levels were lower. Serum calcium, LA diameter, and LVMI values were closely correlated with CF-PWV. In the ROC analysis, the AUROC was calculated as 0.825 for calcium level to determine the patients with increased CF-PWV. When the serum calcium value was taken as 10 mg/dL, it was determined with CF-PWV > 10 m/s were 79.5% sensitivity and 78.2% specificity. CONCLUSION:CF-PWV significantly increases in newly diagnosed hypertensive patients with PHP and significantly related to serum calcium level. To protect against target organ damage, high serum calcium levels should be monitored as well as blood pressure in hypertensive patients with PHP.
10.1007/s40477-020-00512-4
Plasma uric acid is related to large arterial stiffness but not to other hemodynamic variables: a study in 606 normotensive and never-medicated hypertensive subjects.
BMC cardiovascular disorders
BACKGROUND:Elevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial. METHODS:We investigated in a cross-sectional setting the association of PUA with hemodynamics in 606 normotensive and never-medicated hypertensive subjects (295 men, 311 women, age range 19-73 years) without cardiovascular disease or gout. In all except 15 individuals, PUA was within the normal range. Supine hemodynamics were recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis. RESULTS:The mean concentrations of PUA in age, sex and body mass index adjusted quartiles were 234, 278, 314, and 373 µmol/l, respectively. The highest PUA quartile presented with higher aortic to popliteal pulse wave velocity (PWV) than the lowest quartile (8.7 vs. 8.2 m/s, p = 0.026) in analyses additionally adjusted for plasma concentrations of C-reactive protein, low density lipoprotein cholesterol, triglycerides, and mean aortic blood pressure. No differences in radial and aortic blood pressure, wave reflections, heart rate, cardiac output, and systemic vascular resistance were observed between the quartiles. In linear regression analysis, PUA was an independent explanatory factor for PWV (β = 0.168, p < 0.001, R of the model 0.591), but not for systolic or diastolic blood pressure. When the regression analysis was performed separately for men and women, PUA was an independent predictor of PWV in both sexes. CONCLUSIONS:PUA concentration was independently and directly associated with large arterial stiffness in individuals without cardiovascular disease and PUA levels predominantly within the normal range. Trial registration ClinicalTrials.gov NCT01742702.
10.1186/s12872-021-02072-9
Relationship between carotid-femoral pulse wave velocity and uric acid in subjects with hypertension and hyperuricemia.
Liu Jinbo,Wang Kuanting,Liu Huan,Zhao Hongwei,Zhao Xiaoxiao,Lan Yang,Huang Wei,Wang Hongyu
Endocrine journal
Increasing of arterial stiffness is the pathophysiological characteristic of hypertension. Carotid-femoral pulse wave velocity (CF-PWV) is an index of arterial stiffness. Serum uric acid has been found to be involved the development of hypertension. We investigated the relationship between CF-PWV and serum uric acid in subjects with hypertension and hyperuricemia. 651 subjects (M/F 271/380) were divided into four groups, group 1: subjects without hypertension and hyperuricemia; group 2: hypertension subjects without hyperuricemia; group 3: hyperuricemia subjects without hypertension; group 4: subjects with hypertension and hyperuricemia. CF-PWV was measured by Complior apparatus. Results showed that levels of CF-PWV (10.75 ± 2.03 vs. 10.06 ± 1.98 m/s, p < 0.001) and serum uric acid (319.33 ± 80.12 vs. 298.78 ± 74.88 umol/L, p = 0.001) were significantly higher in hypertensive (groups 2 + 4) group than in normotensive (groups 1 + 3) group. CF-PWV was significantly higher in group 4 than group 1, group 2 and group 3 (ANOVA analysis: F = 13.348, p < 0.001; 11.78 ± 2.10 vs. 9.98 ± 1.98, 10.52 ± 1.93, 10.56 ± 1.99 m/s, all p < 0.05, respectively). There was positive correlation between CF-PWV and serum uric acid in entire study group (r = 0.187, p < 0.001), even after adjusting for gender, body mass index, systolic blood pressure (SBP) and diastolic blood pressure (r = 0.100, p = 0.015). Multiple linear regressions showed that SBP, age, benzbromarone, statin and serum uric acid were independent associating factors of CFPWV in all subjects (β = 0.310, p < 0.001; β = 0.330, p < 0.001; β = 0.172, p = 0.002; β = -0.143, p = 0.006; β = 0.126, p = 0.027; respectively). In conclusions, CF-PWV was significantly higher in hypertension subjects with hyperuricemia compared to hypertension without hyperuricemia subjects, and serum uric acid was an independent associating factor of CF-PWV.
10.1507/endocrj.EJ18-0570
Association between uric acid and pulse wave velocity in hypertensive patients and in the general population: a systematic review and meta-analysis.
Rebora Paola,Andreano Anita,Triglione Nicola,Piccinelli Enrico,Palazzini Matteo,Occhi Lucia,Grassi Guido,Valsecchi Maria Grazia,Giannattasio Cristina,Maloberti Alessandro
Blood pressure
The association between serum uric acid (SUA) and pulse wave velocity (PWV), has been extensively evaluated but with some discrepancies in results. A further limitation refers to the fact that only few data were analyzed taking into account the possible effects of gender. The purpose of this study was to estimate the association between SUA and arterial stiffness in general population and hypertensive patients, as a whole population and as divided by gender, by pooling results from existing studies. Carotid-femoral and brachial-ankle PWV (cf- and ba-PWV) have been analyzed separately and subgroup analyses by gender are reported. Among 692 potentially relevant works, 24 articles were analyzed. Seven studies referred to cf-PWV in the general population with an overall positive association at adjusted analysis for both males and females (beta regression coefficient (ß): 0.07; 95%CI: 0.03; 0.11 and ß: 0.06; 95%CI: 0.03; 0.09, respectively). Twelve studies referred to ba-PWV in the general population with the finding of a positive association at adjusted analysis for females (ß: 0.04; 95% confidence interval (CI): 0.01;0.07), but not for males (ß: 0.13; 95%CI: -0.09; 0.34). In hypertensive patients only four studies evaluated cf-PWV and one ba-PWV with only one study (with cf-PWV) finding positive association. The association between SUA and cf-PWV resulted significant in general population in both males and females while it was only significant for female regarding ba-PWV. Furthermore, the few available studies found no significant relationship between SUA and both cf- and ba-PWV in hypertensive subjects.
10.1080/08037051.2020.1735929
Uric Acid and Vascular Damage in Essential Hypertension: Role of Insulin Resistance.
Nutrients
Increased levels of uric acid (UA) have been shown to be correlated with many clinical conditions. Uric acid may adversely affect the insulin signalling pathway inducing insulin resistance (IR). Several studies report the association between arterial stiffness (AS), an early indicator of atherosclerosis, and UA. The purpose of the present study was to evaluate the association between UA and AS, considering the potential role of IR. We enrolled 1114 newly diagnosed, never-treated hypertensive patients. Insulin resistance was assessed by the homeostatic model assessment (HOMA) index. Arterial stiffness was evaluated as the measurement of the carotid-femoral pulse wave velocity (PWV). The study cohort was divided into subgroups, according to increasing tertiles of UA. The mean values of UA were 5.2 ± 1.6 mg/dL in the overall population. Pulse wave velocity was linearly correlated with UA ( < 0.0001), HOMA ( < 0.0001), high sensitivity C-reactive protein ( < 0.0001), systolic blood pressure ( < 0.0001) and LDL cholesterol ( = 0.005). Uric acid was the strongest predictor of PWV and was associated with the highest risk for increased AS. The interaction analysis showed that the joint effect of increased UA and HOMA was significantly higher than that expected in the absence of interaction under the additive model, indicating that the two biomarkers synergically interacted for promoting vascular damage. Our data showed that UA interacted with IR to increase AS in a large cohort of newly diagnosed, never-treated hypertensive patients.
10.3390/nu12092509
Uric acid and arterial stiffness in children and adolescents: Role of insulin resistance and blood pressure.
Frontiers in cardiovascular medicine
Several studies describe the association between serum uric acid (SUA) and arterial stiffness in adults. Uric acid contributes through several mechanisms to the increase in blood pressure (BP) and adversely affects the insulin signaling pathway. Moreover, SUA predict the development of hypertension and insulin resistance up to type 2 diabetes. Early arterial stiffening, estimated by carotid-femoral pulse wave velocity (PWV), may already be present in pediatric age. Aim of our study was to investigate the relationship between SUA and PWV in a pediatric population and its interaction with insulin resistance and BP. In 322 children and adolescents (56.2% male, mean age 11.3 [SD 2.8] years), we measured weight, height, waist circumference, BP and PWV. We also assayed SUA and estimated glomerular filtration rate (eGFR) and calculated HOMA-index as a marker of insulin resistance. Simple and multiple regression analyses were performed to assess variables associated with PWV. Mediation models were applied to identify the direct and indirect effects of individual variables on PWV. On univariate analysis, age ( < 0.001), waist circumference-to-height ratio ( = 0.036), systolic and diastolic BP (SBP and DBP) score ( < 0.001), heart rate ( = 0.028), SUA ( = 0.002), HOMA-index ( < 0.001), and eGFR ( = 0.014) were significantly associated with PWV. The multiple regression model showed that only age ( = 0.028), SBP score ( = 0.006), and heart rate ( = 0.001) were significantly associated with PWV. The results were superimposable when the DBP score replaced the SBP score in the model. Mediation models showed that the effect of eGFR on PWV was fully mediated by SUA ( = 0.015) and that the effect of SUA on PWV was totally mediated by HOMA-index ( < 0.001). Both SUA ( < 0.01) and HOMA-index ( < 0.01) had a significant association with higher SBP (DBP) scores. The double mediation model including both BP and HOMA-index showed that the SUA effect on PWV was totally mediated by both variables ( = 0.005, for HOMA-index, = 0.004, for SBP score and = 0.007, for combined effect). The results were superimposable when the DBP score replaced the SBP score in the model. In conclusion, insulin resistance and BP are both important mediators of the association between SUA and vascular stiffness in pediatric age.
10.3389/fcvm.2022.978366