Progression of Arterial Stiffness is Associated With Midlife Diastolic Blood Pressure and Transition to Late-Life Hypertensive Phenotypes.
ABSTRACT: Background Hypertension-associated cardiovascular events are particularly associated with elevated systolic blood pressure (SBP) in late life, yet long-term interactions between SBP, diastolic BP (DBP) and arterial stiffness in development of late-life hypertensive phenotypes remain unclear. Methods and Results In the UK Biobank, we determined associations between arterial stiffness index (ASI), SBP, DBP, and their progression, and transition from normotension (<140/90 mm Hg) to hypertension or elevated ASI (>10 m/s). Associations were determined by general linear and logistic regression, adjusted for cardiovascular risk factors and variability of measurements across follow-ups. Mean values of baseline SBP, DBP, and ASI were determined stratified by deciles of age, blood pressure, and ASI, with CIs determined by bootstrapping. In 169 742 participants at baseline, ASI was more strongly associated with DBP than SBP, before and after adjustment for risk factors (?: SBP, -0.01 [P<0.001]; DBP, 0.06 [P<0.001]), while DBP was more strongly associated with progression of ASI (n=13 761; ?: SBP, 0.013 [P=0.01]; DBP, 0.038 [P<0.001]). Baseline ASI was associated with increasing SBP during follow-up (?=0.02, P<0.001) but not DBP (?=0.0004, P=0.39), but was associated with a younger age of transition from rising to falling DBP (highest versus lowest quartile: 51.2; 95% CI, 49.9-52.3 versus 60.4; 95% CI, 59.6-61.3 [P<0.001]). ASI predicted the development of isolated systolic hypertension (odds ratio, 1.30; 95% CI, 1.22-1.39), particularly after adjustment for measurement variability (odds ratio, 2.29). Conclusions Midlife DBP was the strongest predictor of progression of arterial stiffness, while arterial stiffness was associated with earlier transition to a falling DBP. Prevention of long-term harms associated with arterial stiffness may require more intensive control of midlife DBP.
Project description:Primary aldosteronism not only results in hypertension but also stiffer arteries. The time course and factors predicting the reversal of arterial stiffness after treatment are unclear. We prospectively enrolled 102 patients with aldosterone-producing adenoma (APA) from March 2006 to January 2012. We measured the pulse wave velocity (PWV) between brachial-ankle (baPWV) and heart-ankle (haPWV) before, 6 and 12 months after their adrenalectomy. After treatment, the PWV decreased significantly during the first 6 months (both p < 0.001), but no further reduction in the following 6 months. The determinant factors for baseline baPWV were age, duration of hypertension, and baseline systolic blood pressure (SBP) in multivariate linear regression analysis, similar with baseline haPWV (determinants: age, duration of hypertension, baseline SBP and diastolic blood pressure (DBP)). In multivariate linear regression analysis, the decrease in DBP at 6 months (ΔDBP0-6mo) and baseline baPWV were significantly associated with the decrease in baPWV at 6 months (ΔbaPWV0-6mo). The associated factors of the change in haPWV at 6 months (ΔhaPWV0-6mo) were baseline haPWV, ΔDBP0-6mo and change in log-transformed plasma renin activity. Our result suggested that reversal of arterial stiffness in APA patients occurred early after adrenalectomy and determined by baseline vascular condition, hemodynamic factors, and humoral factors.
Project description:OBJECTIVE:Patients with inflammatory joint diseases (IJD) have a high prevalence of hypertension and increased arterial stiffness. The aim of the present study was to evaluate the effect of long-term rosuvastatin treatment on arterial stiffness, measured by augmentation index (AIx) and aortic pulse wave velocity (aPWV), and blood pressure (BP) in IJD patients with established atherosclerosis. METHODS:Eighty-nine statin naïve IJD patients with carotid atherosclerotic plaque(s) (rheumatoid arthritis n = 55, ankylosing spondylitis n = 23, psoriatic arthritis n = 11) received rosuvastatin for 18 months to achieve low-density lipoprotein cholesterol goal ?1.8 mmol/L. Change in AIx (?AIx), aPWV (?aPWV), systolic BP (?sBP) and diastolic BP (?dBP) from baseline to study end was assessed by paired samples t-tests. Linear regression was applied to evaluate associations between cardiovascular disease (CVD) risk factors, rheumatic disease specific variables and medication, and ?AIx, ?aPWV, ?sBP and ?dBP. RESULTS:AIx, aPWV, sBP and dBP were significantly reduced from baseline to study end. The mean (95%CI) changes were: ?AIx: -0.34 (-0.03, -0.65)% (p = 0.03), ?aPWV: -1.69 (-0.21, -3.17) m/s2 (p = 0.03), ?sBP: -5.27 (-1.61, -8.93) mmHg (p = 0.004) and ?dBP -2.93 (-0.86, -5.00) mmHg (p = 0.01). In linear regression models, ?aPWV was significantly correlated with ?sBP and ?dBP (for all: p<0.001). CONCLUSIONS:There is an unmet need of studies evaluating CVD prevention in IJD patients. We have shown for the first time that long-term intensive lipid lowering with rosuvastatin improved arterial stiffness and induced a clinically significant BP reduction in patients with IJD. These improvements were linearly correlated and may represent novel insight into the pleiotropic effects by statins. TRIAL REGISTRATION:ClinicalTrials.gov NCT01389388.
Project description:Brachial-ankle pulse wave velocity (baPWV), as a marker of arterial stiffness, has been demonstrated to be associated with blood pressure (BP) and onset of hypertension. However, little information is available on the associations between baPWV and BP indices [systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), mean arterial pressure (MAP)] in treated hypertensive patients. We aimed to assess the associations between BP indices and baPWV. In this cross-sectional study, 14,598 hypertensive patients from China Stroke Primary Prevention Trial (CSPPT) at the exit visit of the trial were analyzed. Elevated baPWV was defined as ?18.3?m/s. Multivariate linear and logistic regression analyses were performed to evaluate the associations of BP indices with baPWV and elevated baPWV. Moreover, the smooth curve fitting (penalized spline method) was conducted. Multivariate linear regression analyses showed that continuous SBP, DBP, PP and MAP were independently and positively associated with baPWV (??=?0.081, 0.084, 0.078 and 0.115, respectively, all P?<?0.001). Compared with controlled SBP group (<140?mm Hg), uncontrolled SBP (?140?mm Hg) was significantly associated with higher baPWV [??=?2.234, 95% confidence interval (CI): 2.137-2.332]. Similarly, compared with controlled DBP group (<90?mm Hg), uncontrolled DBP (?90?mm Hg) was significantly associated with higher baPWV (??=?1.466, 95%CI: 1.341-1.590). Multiple logistic analyses also showed that SBP, DBP, PP and MAP were significantly and positively associated with elevated baPWV (OR?=?1.056, 1.049, 1.052, and 1.075, respectively, all P?<?0.001). The fully-adjusted smooth curve fitting presented a linear association between BP indices with baPWV. In conclusion, among treated hypertensive patients, SBP, DBP, PP and MAP levels were independently and positively associated with baPWV and elevated baPWV, suggesting that baPWV might be a way to predict uncontrolled BP.
Project description:About one quarter of adults are hypertensive and high blood pressure carries increased risk for heart disease, stroke, kidney disease and death. Increased arterial stiffness is a key factor in the pathogenesis of systolic hypertension and cardiovascular disease. Substantial heritability of blood-pressure (BP) and arterial-stiffness suggests important genetic contributions.In Framingham Heart Study families, we analyzed genome-wide SNP (Affymetrix 100K GeneChip) associations with systolic (SBP) and diastolic (DBP) BP at a single examination in 1971-1975 (n = 1260), at a recent examination in 1998-2001 (n = 1233), and long-term averaged SBP and DBP from 1971-2001 (n = 1327, mean age 52 years, 54% women) and with arterial stiffness measured by arterial tonometry (carotid-femoral and carotid-brachial pulse wave velocity, forward and reflected pressure wave amplitude, and mean arterial pressure; 1998-2001, n = 644). In primary analyses we used generalized estimating equations in models for an additive genetic effect to test associations between SNPs and phenotypes of interest using multivariable-adjusted residuals. A total of 70,987 autosomal SNPs with minor allele frequency > or = 0.10, genotype call rate > or = 0.80, and Hardy-Weinberg equilibrium p > or = 0.001 were analyzed. We also tested for association of 69 SNPs in six renin-angiotensin-aldosterone pathway genes with BP and arterial stiffness phenotypes as part of a candidate gene search.In the primary analyses, none of the associations attained genome-wide significance. For the six BP phenotypes, seven SNPs yielded p values < 10(-5). The lowest p-values for SBP and DBP respectively were rs10493340 (p = 1.7 x 10(-6)) and rs1963982 (p = 3.3 x 10(-6)). For the five tonometry phenotypes, five SNPs had p values < 10(-5); lowest p-values were for reflected wave (rs6063312, p = 2.1 x 10(-6)) and carotid-brachial pulse wave velocity (rs770189, p = 2.5 x 10(-6)) in MEF2C, a regulator of cardiac morphogenesis. We found only weak association of SNPs in the renin-angiotensin-aldosterone pathway with BP or arterial stiffness.These results of genome-wide association testing for blood pressure and arterial stiffness phenotypes in an unselected community-based sample of adults may aid in the identification of the genetic basis of hypertension and arterial disease, help identify high risk individuals, and guide novel therapies for hypertension. Additional studies are needed to replicate any associations identified in these analyses.
Project description:Although the association between high blood pressure (BP), particularly in midlife, and late-life dementia is known, less is known about variations by race and sex. In a prospective national study of 22?164 blacks and whites ?45 years without baseline cognitive impairment or stroke from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke), enrolled 2003 to 2007 and followed through September 2015, we measured changes in cognition associated with baseline systolic and diastolic BP (SBP and DBP), as well as pulse pressure (PP) and mean arterial pressure, and we tested whether age, race, and sex modified the effects. Outcomes were global cognition (Six-Item Screener; primary outcome), new learning (Word List Learning), verbal memory (Word List Delayed Recall), and executive function (Animal Fluency Test). Median follow-up was 8.1 years. Significantly faster declines in global cognition were associated with higher SBP, lower DBP, and higher PP with increasing age ( P<0.001 for age×SBP×follow-up-time, age×DBP×follow-up-time, and age×PP×follow-up-time interaction). Declines in global cognition were not associated with mean arterial pressure after adjusting for PP. Blacks, compared with whites, had faster declines in global cognition associated with SBP ( P=0.02) and mean arterial pressure ( P=0.04). Men, compared with women, had faster declines in new learning associated with SBP ( P=0.04). BP was not associated with decline of verbal memory and executive function, after controlling for the effect of age on cognitive trajectories. Significantly faster declines in global cognition over 8 years were associated with higher SBP, lower DBP, and higher PP with increasing age. SBP-related cognitive declines were greater in blacks and men.
Project description:Endothelial dysfunction and vascular smooth muscle cell (VSMC) plasticity are critically involved in the pathogenesis of hypertension and arterial stiffness. MicroRNAs can mediate the cellular communication between vascular endothelial cells (ECs) and neighboring cells. Here, we investigated the role of endothelial-derived extracellular microRNA-92a (miR-92a) in promoting arterial stiffness by regulating EC-VSMC communication. Serum miR-92a level was higher in hypertensive patients than controls. Circulating miR-92a level was positively correlated with pulse wave velocity (PWV), systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum endothelin-1 (ET-1) level, but inversely with serum nitric oxide (NO) level. In vitro, angiotensin II (Ang II)-increased miR-92a level in ECs mediated a contractile-to-synthetic phenotype change of co-cultured VSMCs. In Ang II-infused mice, locked nucleic acid-modified antisense miR-92a (LNA-miR-92a) ameliorated PWV, SBP, DBP, and impaired vasodilation induced by Ang II. LNA-miR-92a administration also reversed the increased levels of proliferative genes and decreased levels of contractile genes induced by Ang II in mouse aortas. Circulating serum miR-92a level and PWV were correlated in these mice. These findings indicate that EC miR-92a may be transported to VSMCs via extracellular vesicles to regulate phenotype changes of VSMCs, leading to arterial stiffness.
Project description:Background To understand how blood pressure ( BP ) from midlife and beyond is related to cognition in older age, a lifespan approach is needed. We assessed the associations of BP levels and variability from midlife on with subsequent cognitive change. Methods and Results The ARIC (Atherosclerosis Risk in Communities) Study participants underwent 4 clinic BP measurements (visit 1, 2, 3, and 4 BP s) between 1987 and 1998, and their mean levels and average real variability ( ARV ) were assessed as exposures. A global cognitive z score, estimated from the Delayed Word Recall Test, Digit Symbol Substitution Test, and Word Fluency Test scores, was calculated at 1996 to 1998 (visit 4) and 2011 to 2013 (visit 5). Among 11 408 participants (mean age, 54 years; 56% women; 21% black race), mean systolic BP ( SBP )/diastolic BP ( DBP ) level was 123/72 mm Hg, and ARVSBP / ARVDBP was 11/7 mm Hg. With linear mixed models, 1- SD increases of ARVSBP (standardized regression coefficient [95% confidence interval], -0.03 [-0.04 to -0.01] points) and ARVDBP (standardized regression coefficient [95% confidence interval], -0.02 [-0.03 to -0.002] points; both P<0.05), but not mean SBP or DBP levels, were associated with lower global cognitive z scores at visit 4. In contrast, mean SBP (standardized regression coefficient [95% confidence interval], -0.04 [-0.06 to -0.02] points) or DBP (standardized regression coefficient [95% confidence interval], 0.04 [0.02-0.06] points; both P<0.001) level, but not ARVSBP or ARVDBP , was associated with change in global cognitive z scores from visits 4 to 5. Conclusions Greater visit-to-visit SBP or DBP variability from midlife on is modestly associated with lower cognitive function, whereas higher mean SBP and lower DBP levels from midlife to later life are modestly associated with cognitive decline in later life.
Project description:Arterial stiffness is an important factor in hypertension. Fibulin 2 is an extracellular matrix scaffold protein involved in arterial stiffness and, hence, the fibulin 2 (FBLN2) gene may be a candidate for hypertension susceptibility. 4 single nucleotide polymorphisms (SNPs) of FBLN2 were evaluated in an association case-control study containing 447 hypertensive patients and 344 normotensive control subjects. The minor allele frequencies of rs3732666 and rs1061376 were significantly lower in hypertensives. The odds ratios (OR) for having the protective G (rs3732666) and T (rs1061376) alleles were 0.75 (95%CI: 0.58 to 0.96) and 0.83 (95%CI: 0.66 to 1.02), respectively. For rs3732666, the OR for hypertension in AG+GG subjects, compared with AA, was 0.71 (95%CI: 0.52 to 0.95). The protective genotype AG+GG was associated with significantly lower systolic blood pressure (SBP) [-3.6 mmHg (P = 0.048)]. There was a significant age interaction with rs3732666; the effect decreasing with increasing age. For rs1061376, TT subjects had an OR for hypertension of 0.53 (95%CI: 0.32 to 0.87) compared with CC subjects, with reduced SBP (-7.91 mmHg; P = 0.008) and diastolic BP (DBP) (-3.69 mmHg; P = 0.015). The presence of a G allele was an independent predictor of intima-media thickness (IMT); G carrier's having lower mean IMT (-0.037 mm, P = 0.027) compared with AA. Our results provide the first evidence for FBLN2 as a new gene associated with hypertension.
Project description:<h4>Objective</h4>To test whether a synonymous single nucleotide polymorphism (A?G; rs700518) in the CYP19A1 gene, which encodes the enzyme aromatase, is associated with an increased risk for hypertension of midlife women.<h4>Methods</h4>In a cross-sectional study, 639 midlife women were recruited. Eligible women had their blood pressure, weight and height measured, and donated a blood sample for hormone and genetic analyses. The participants also completed a detailed study survey. Women were grouped according to their genotype, blood pressure measurements, and medical history. The data were analyzed using logistic and linear regression models. The study had 80% power to detect small differences in mean systolic blood pressure (SBP; 4.5 mmHg) and diastolic blood pressure (DBP; 3 mmHg).<h4>Results</h4>The selected polymorphism was significantly associated with hypertension and SBP in unadjusted analyses. Interestingly, women with hypertension were more likely to be homozygous for the A allele (AA) compared to women who were not categorized as having hypertension. Further, the mean SBP was significantly higher for women who were homozygous for the A allele when compared to women carrying the other genotypes (AG or GG). The unadjusted association between DBP values and genotype was of borderline statistical significance (p=0.07). However, after adjustment for potential confounders (age, race, body mass index (BMI), smoking and physical activity), the associations between genotype and hypertension/blood pressure were attenuated and not statistically significant.<h4>Conclusion</h4>The rs700518 polymorphism in the CYP19A1 is not associated with hypertension in our sample of midlife women. Other factors, including race and BMI, appear to play a greater role.
Project description:<h4>Background</h4>Reports on the relative importance of the diastolic and systolic blood pressures (DBP and SBP) in age-related cognitive decline are mixed. Investigating the relation between DBP/SBP and functional and structural brain changes could elucidate which of the 2 measures is more critically important for brain function and, consequently, cognitive impairment.<h4>Methods</h4>We investigated the association of SBP and DBP with cortical volume, cerebral blood flow (CBF), and white matter lesions (WML), in nondemented older adults with and without mild cognitive impairment (MCI; N = 265, 185 MCI, mean age = 64 years). Brachial blood pressure was measured twice while seated, and the average of the 2 measures was used. Cortical volume, gray matter (GM) CBF, and WML were estimated using T1-weighted imaging, arterial spin labeling, and fluid attenuation inversion recovery, respectively.<h4>Results</h4>Reduced cortical volume was associated with elevated DBP (?= -0.18, P = 0.034) but not with SBP (? = -0.10, P = 0.206). GM CBF was associated with DBP (? = -0.13, P = 0.048) but not with SBP (? = -0.07, P = 0.275). Likewise, CBF within brain regions where MCI patients showed hypoperfusion were only associated with DBP (DBP: ? = -0.17, P = 0.005; SBP: ? = -0.09, P = 0.120). WML volume was associated with both DBP (? = 0.20, P = 0.005) and SBP (? = 0.30, P < 0.001). For all measures, there was no interaction between DBP/SBP and cognitive status, indicating that these associations were independent of the cognitive status.<h4>Conclusions</h4>Independently of the cognitive status, DBP is more critically important for GM volume and perfusion, whereas WML is associated with both blood pressures, likely reflecting long-term effect of hypertension and autoregulation dysfunction.