Progression Of Systolic Blood Pressure Research Articles

Increasing liver fat is associated with progression of cardiovascular risk factors.

Nonalcoholic fatty liver disease is associated with cardiovascular risk factors in cross-sectional analyses. However, less is known about how changes in liver fat associate with the progression of cardiovascular risk factors. A substudy (n=808) drawn from the Framingham Heart Study underwent serial computed tomography scans 6years apart. We performed multivariable-adjusted regression to determine the association between changes in liver fat and progression of cardiovascular risk factors. Each standard deviation increase in liver fat was associated with adverse progression of systolic blood pressure, diastolic blood pressure, fasting glucose, high-density lipoprotein and log triglycerides. After adjusting for baseline cardiovascular risk, baselinebody mass index (BMI),and change in BMI, increasing liver fat was significantly associated with adverse changes in fasting glucose and triglycerides. In a longitudinal cohort, increasing liver fat over 6years was associated with progression of cardiovascular risk factors, even after accounting for BMI changes.

Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium.

AimsAveraged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.Methods and resultsAn individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.ConclusionAveraged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

A15274 Progression of arterial stiffness in the Elderly Chinese

Objectives: Brachial-ankle pulse wave velocity (baPWV) is a measure of arterial stiffness and predicts cardiovascular events and mortality in previous studies. In the present study, we investigated several years’ progression of baPWV and its risk factors in an elderly (≥60 years) Chinese population. Methods: We measured brachial-ankle pulse wave velocity annually using an automated cuff device from 2006 to 2013. Regression coefficient against the baPWV value and the duration across examinations was used to evaluate annual progression of baPWV. The progression of systolic blood pressure (SBP) and diastolic blood pressure (DBP) was also calculated. Results: A total of 1054 subjects (59% women; mean baseline age, 67.1 years), completed at least 3 times (from 3 to 7) of baPWV examination. With a mean follow up of 4.4 years, an annual progression rate of baPWV was 0.20 m/s/y in general. The progression of baPWV was significantly associated with baseline age (+0.09 m/s/y for 10 years older, P = 0.004), and with the progression of SBP (correlation coefficient: 0.50, P < 0.0001) and DBP (correlation coefficient: 0.48, P < 0.0001), but not with baseline SBP or DBP (P > 0.10). With an adjustment for baseline age and other covariables, 1 mm Hg annual progression rate of SBP and DBP was significantly (P < 0.0001) associated with a progression rate of baPWV for 0.05 m/s/y and 0.06 m/s/y, respectively. Conclusion: Arterial stiffness progression develops in elderly Chinese, and significantly associates with the progression of blood pressure.

Arterial stiffness and progression of cerebral white matter lesions in asymptomatic patients with type 2 diabetes and matched controls: A 5-year cohort study

AimStroke is a frequent and feared complication in patients with type 2 diabetes. Arterial stiffness may improve current suboptimal risk prediction of stroke. However, studies in diabetes populations are lacking. We investigated the association between arterial stiffness progression (carotid-femoral pulse wave velocity [PWV]) and the progression of cerebral white matter lesions (WML), a marker of stroke risk, in patients with type 2 diabetes and matched controls.MethodsIn a 5-year follow-up study, data from 49 patients and 58 controls were available for analysis. At baseline, participants had a mean (±SD) age of 59 ± 10 years and patients had a median (range) diabetes duration of 1.8 (1.0–3.2) years. Fifty-two (49%) were males. At both baseline and follow-up, PWV was obtained by tonometry and WML by cerebral T2-FLAIR MRI. WML was assessed by Breteler score, and progression was defined as an upward change in category during follow-up.ResultsPatients with type 2 diabetes had a higher PWV than controls at both baseline (9.2 ± 2.2 vs. 7.9 ± 1.4m/s, p<0.01) and follow-up (9.8 ± 2.4 vs. 8.6 ± 1.9m/s, p = 0.01). Breteler scores and WML progression were similar in the two groups (p>0.05). PWV progression was associated with WML progression in the total cohort (adjusted for age, sex, diabetes, baseline PWV and systolic blood pressure progression: OR 1.58 [95%CI: 1.09–2.28], p = 0.02). We found no interaction between diabetes and PWV progression on WML progression.ConclusionsPWV progression is associated with WML progression in patients with type 2 diabetes and healthy controls. PWV candidates as a new risk marker for stroke.

Analysis of the progression of systolic blood pressure using imputation of missing phenotype values.

We present a genome-wide association study of a quantitative trait, "progression of systolic blood pressure in time," in which 142 unrelated individuals of the Genetic Analysis Workshop 18 real genotype data were analyzed. Information on systolic blood pressure and other phenotypic covariates was missing at certain time points for a considerable part of the sample. We observed that the dropout process causing missingness is not independent of the initial systolic blood pressure; that is, the data is not missing completely at random. However, after the adjustment for age, the impact of systolic blood pressure on dropouts was no longer significant. Therefore, we decided to impute missing phenotype values by using information from individuals with complete phenotypic data. Progression of systolic blood pressure (∆SBP/∆t) was defined based on the imputed phenotypes and analyzed in a genome-wide fashion. We also conducted an exhaustive genome-wide search for interaction between single-nucleotide polymorphisms (7.14 × 1010 tests) under an allelic model.The suggested data imputation and the association analysis strategy proved to be valid in the sense that there was no evidence of genome-wide inflation or increased type I error in general. Furthermore, we detected 2 single-nucleotide polymorphisms (SNPs) that met the criterion for genome-wide significance (p≤5 × 10−8), which was also confirmed via Monte-Carlo simulation. In view of the rather small sample size, however, the results have to be followed-up in larger studies.

Life Course Trajectories of Systolic Blood Pressure Using Longitudinal Data from Eight UK Cohorts

Much of our understanding of the age-related progression of systolic blood pressure (SBP) comes from cross-sectional data, which do not directly capture within-individual change. We estimated life course trajectories of SBP using longitudinal data from seven population-based cohorts and one predominantly white collar occupational cohort, each from the United Kingdom and with data covering different but overlapping age periods. Data are from 30,372 individuals and comprise 102,583 SBP observations spanning from age 7 to 80+y. Multilevel models were fitted to each cohort. Four life course phases were evident in both sexes: a rapid increase in SBP coinciding with peak adolescent growth, a more gentle increase in early adulthood, a midlife acceleration beginning in the fourth decade, and a period of deceleration in late adulthood where increases in SBP slowed and SBP eventually declined. These phases were still present, although at lower levels, after adjusting for increases in body mass index though adulthood. The deceleration and decline in old age was less evident after excluding individuals who had taken antihypertensive medication. Compared to the population-based cohorts, the occupational cohort had a lower mean SBP, a shallower annual increase in midlife, and a later midlife acceleration. The maximum sex difference was found at age 26 (+8.2 mm Hg higher in men, 95% CI: 6.7, 9.8); women then experienced steeper rises and caught up by the seventh decade. Our investigation shows a general pattern of SBP progression from childhood in the UK, and suggests possible differences in this pattern during adulthood between a general population and an occupational population. Please see later in the article for the Editors' Summary.

Angiotensin II Stimulates Renin in Inner Medullary Collecting Duct Cells via Protein Kinase C and Independent of Epithelial Sodium Channel and Mineralocorticoid Receptor Activity

Collecting duct (CD) renin is stimulated by angiotensin (Ang) II, providing a pathway for Ang I generation and further conversion to Ang II. Ang II stimulates the epithelial sodium channel via the Ang II type 1 receptor and increases mineralocorticoid receptor activity attributed to increased aldosterone release. Our objective was to determine whether CD renin augmentation is mediated directly by Ang II type 1 receptor or via the epithelial sodium channel and mineralocorticoid receptor. In vivo studies examined the effects of epithelial sodium channel blockade (amiloride; 5 mg/kg per day) on CD renin expression and urinary renin content in Ang II-infused rats (80 ng/min, 2 weeks). Ang II infusion increased systolic blood pressure, medullary renin mRNA, urinary renin content, and intrarenal Ang II levels. Amiloride cotreatment did not alter these responses despite a reduction in the rate of progression of systolic blood pressure. In primary cultures of inner medullary CD cells, renin mRNA and (pro)renin protein levels increased with Ang II (100 nmol/L), and candesartan (Ang II type 1 receptor antagonist) prevented this effect. Aldosterone (10(-10) to 10(-7) mol/L) with or without amiloride did not modify the upregulation of renin mRNA in Ang II-treated cells. However, inhibition of protein kinase C with calphostin C prevented the Ang II-mediated increases in renin mRNA and (pro)renin protein levels. Furthermore, protein kinase C activation with phorbol 12-myristate 13-acetate increased renin expression to the same extent as Ang II. These data indicate that an Ang II type 1 receptor-mediated increase in CD renin is induced directly by Ang II via the protein kinase C pathway and that this regulation is independent of mineralocorticoid receptor activation or epithelial sodium channel activity.

Association Between Adducin-1 G460W Variant and Blood Pressure in Swedes Is Dependent on Interaction With Body Mass Index and Gender

The W allele of the G460W polymorphism in the adducin-1 gene has been occasionally associated with increased blood pressure (BP). The aim of this study was to test whether the G460W variant is associated with BP levels and BP progression rate and whether G460W associations with BP are affected by sex, body mass index (BMI), or age. The G460W polymorphism was genotyped in the population-based Malmö Diet and Cancer-cardiovascular arm (MDC-CVA; n = 6103), of whom 53% had also been examined 11 +/- 4.4 years earlier in the Malmö Preventive Project (MPP). Among subjects without antihypertensive treatment (AHT) in the MDC-CVA (n = 5009), there was no difference between carriers (38%) and noncarriers (62%) of the W allele in systolic BP (139.2 +/- 18.2 v 139.2 +/- 18.5 mm Hg; P = .99) or diastolic BP (85.9 +/- 9.1 v 86.1 +/- 9.2 mm Hg; P = .49). In subjects free from AHT in the MPP and MDC (n = 2637) there was no difference between carriers (38%) and noncarriers (62%) in progression of systolic BP (2.0 +/- 2.5 v 2.0 +/- 2.7 mm Hg/year; P = .45) or diastolic BP (0.59 +/- 1.6 v 0.56 +/- 1.5 mm Hg/year; P = .66) from MPP to MDC. At MDC-CVA BP was influenced by interaction between the G460W and BMI (P = .02 for systolic BP and P = .002 for diastolic BP) and by interaction between G460W and sex (P = .03 for systolic BP and P = .02 for diastolic BP), a result further confirmed by stratified analysis showing that female carriers of the W allele belonging to the upper tertile of BMI had increased systolic BP (146.1 +/- 18.6 v 141.2 +/- 18.6 mm Hg; P < .001), diastolic BP (88.7 +/- 8.7 v 86.1 +/- 8.7 mm Hg; P < .001), and prevalence of hypertension (72.5% v 61.8 %; P = .001). Our data suggest that the G460W polymorphism influences BP when BMI and sex are taken into account.

The functional variant of the CLC-Kb channel T481S is not associated with blood pressure or hypertension in Swedes

A common threonine481serine polymorphism (T481S) has been shown in vitro to strongly activate the chloride channel Kb (CLC-Kb) expressed in the kidney, and the 481S allele has been associated with human hypertension. The study aim was to evaluate the association of the T481S polymorphism with blood pressure (BP) levels and the BP progression rate in Swedes. The cardiovascular cohort of the Malmö Diet and Cancer (MDC) study is a population surveyed in 1991-1996 (n=6103, DNA available on n=6055), 53% of whom had also been examined 11 +/- 4.4 years earlier in the Malmö Preventive Project (MPP). Hypertension was defined as having BP above 140/90 mmHg or being on antihypertensive therapy (AHT). Carriers of one or two copies of the 481S allele were compared with T481T homozygotes (noncarriers). Among individuals without AHT in the MDC study (n=4988) there was no difference between carriers (n=1164, 23%) and noncarriers (n=3824, 77%) in systolic BP (139.3 +/- 8.3 vs 139.2 +/- 8.3 mmHg, P = 0.82) or diastolic BP (86.0 +/- 9.1 vs 86.0 +/- 9.2 mmHg, P = 0.95). In subjects free from AHT at the MPP and MDC studies (n=2627) there was no difference between carriers (n=607, 23%) and noncarriers (n=2020, 77%) in progression of systolic BP (2.1 +/- 2.6 vs 2.0 +/- 2.8 mmHg/year, P = 0.72) or diastolic BP (0.57 +/- 1.4 vs 0.58 +/- 1.6 mmHg/year, P = 0.85) from MPP to MDC. Multivariate analysis gave no support of interaction between the CLC-Kb T481S polymorphism, gender, age or body mass index regarding their effect on BP. Our data do not support a role of the CLC-Kb T481S polymorphism in BP regulation in Swedes.

Parental Longevity and 7-Year Changes in Blood Pressures in Adult Offspring

In this report, we examined the cross-sectional and the 7-year longitudinal changes in blood pressures in adult offspring according to parental longevity. A population of volunteers free of symptomatic cardiovascular diseases who participated to the Supplementation en Vitamines et en Minéraux Antioxydants (SUVIMAX) Vascular Study (mean age 52.3 years; 48.3% women) were examined at baseline and 7 years later. Paternal (n=994) and maternal (n=896) longevity were analyzed separately. The prevalence of hypertension at baseline in subjects whose father died at <65 years of age, in those whose fathers were alive by age 65 but died by 80 years of age, and in those whose fathers were alive by age 80 was respectively 34.9%, 28.5%, and 20.2% (P<0.001). The means of systolic blood pressure in the 3 groups of paternal longevity were respectively 128.4 (+/-16.0), 125.3 (+/-14.2), and 123.6 (+/-14.4) mm Hg (P<0.001). During the follow-up, the mean systolic blood pressure increases in the 3 groups of paternal longevity were respectively 5.3 (+/-17.0), 4.2 (+/-14.0), and 1.6 (+/-13.2) mm Hg (P<0.001). In subjects without hypertension at baseline, hypertension occurred during the follow-up in 26.6%, 17.7%, and 15.3% (P<0.009), respectively. Multivariate analyses adjusted for baseline or changes in cardiovascular risk factors did not modify these results. In contrast, there was no relationship between maternal longevity and blood pressure measurements in either cross-sectional or longitudinal analyses. This study suggests that paternal premature death was associated with accelerated progression of systolic blood pressure and higher occurrence of hypertension in offspring. These results indicate that there are dynamic and continuous processes linking paternal longevity to blood pressure in adults.

Determinants of cardiorenal damage progression in normotensive and never-treated hypertensive subjects

In the present longitudinal study, we attempted to identify the determinants of cardiorenal damage progression in normotensive subjects (<140/90 mm Hg) and patients with never-treated essential hypertension. Renal hemodynamics and function and cardiac morphology were evaluated by isotopic techniques and echocardiography at baseline and after a median follow-up period of 5.2 years (range 3 to 13) in 30 normotensive and 33 hypertensive subjects. The results are mean +/- SD. Among normotensive subjects at baseline, 50% became hypertensive during follow-up. In the whole population, multivariate analysis showed that age was the main determinant of the progression of systolic blood pressure. The yearly change in glomerular filtration rate (GFR) was exaggerated in hypertensive when compared to normotensive subjects at baseline (-1.22 +/- 2.71 vs. 0.12 +/- 2.08 mL/min/year, respectively) (P= 0.033). In the whole population, only baseline systolic blood pressure remained correlated to the change in GFR, independently of GFR at baseline (model r(2)= 0.44) (P < 0.0001). The observed increase in albuminuria was correlated with change in blood pressure only in hypertensive subjects at baseline. Left ventricular mass (LVM) progression was significant only in men and its determinants were basal plasma aldosterone, serum uric acid, and triglyceride and change in systolic blood pressure (r(2)= 0.71) (P < 0.0001). In a population of untreated subjects, baseline blood pressure as well as progression of blood pressure during follow-up are the main determinants of the decline in GFR, progression of albuminuria, and LVM.