Long-term Changes In Blood Pressure Research Articles

Habitual coffee consumption and office, home, and ambulatory blood pressure: results of a 10-year prospective study.

Heterogeneous are the results of the published studies aimed at determining the long-term effects of habitual coffee consumption on blood pressure (BP). Specifically, no data are available on the longitudinal association between habitual coffee consumption and office, home and 24 h BP profile and variability. In 1408 subjects recruited in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, followed for a 10 year follow-up period and classified as coffee consumers and nonconsumers (self-reporting), we prospectically investigated the association between habitual coffee consumption and office, home and 24-h ambulatory BP; 24-h BP variability; and development of a new hypertensive state. Data were also analysed according to gender. When data were adjusted for confounders habitual coffee nonconsumers and consumers displayed similar long-term BP changes during the follow-up in office, home, and ambulatory BP. No difference was found between heavy and moderate coffee consumers. Furthermore, also new-onset hypertension and patterns of BP variability were superimposable in coffee nonconsumers and consumers, independently on confounders including gender, number, and characteristics of the antihypertensive drug treatment. The present study, which is the first longitudinal investigation never performed examining in a prospective fashion the long-term (10 year) effects of coffee consumption on office, home, and ambulatory BP, provides conclusive evidence that habitual coffee consumption is associated with neutral effects on in-office and out-of-office BP values and related variabilities. This is the also the case for the new-onset hypertensive state.

Late outcomes of renal denervation are more favourable than early ones: facts or fancies?

Following second-generation randomized trials, there is evidence that renal denervation (RDN) decreases blood pressure (BP), although to a lesser extent than suggested in the initial controlled and observational studies. The recent publication of the 36-month follow-up of the Symplicity HTN-3 trial has raised expectations, suggesting increasing, late benefits of the procedure, despite initially negative results. These findings come after those obtained at 36months in the sham-controlled trial SPYRAL HTN-ON MED and in the Global Symplicity Registry. However, they are susceptible to biases inherent in observational studies (after unblinding for sham-control) and non-random, substantial attrition of treatment groups at 36 months, and used interpolation of missing BPs. More importantly, in SPYRAL HTN-ON MED and Symplicity HTN-3, long-term BP changes in patients from the initial RDN group were compared with those in a heterogeneous control group, including both control patients who did not benefit from RDN and patients who eventually crossed over to RDN. In crossover patients, the last BP before RDN was imputed to subsequent follow-up. In Symplicity HTN-3, this particular approach led to the claim of increasing long-term benefits of RDN. However, comparison of BP changes in patients from the RDN group and control patients who did not undergo RDN, without imputation of BPs from crossover patients, does not support this view. The good news is that despite the suggestion of sympathetic nerve regrowth after RDN in some animal models, there is no strong signal in favour of a decreasing effect of RDN over time, up to 24 or even 36months. Still, current data do not support a long-term increase in the effect of RDN and the durability of RDN-related BP reduction remains to be formally demonstrated.

Abstract 11963: Blood Level of Coffee-Eelated DNA Methylation and Long-Term Changes in Blood Pressure in Response to Weight-Loss Diet Interventions: The Pounds Lost Trial

Introduction: Coffee intake has been associated with a lower risk of hypertension. Recent epigenome-wide association studies linked DNA methylation (DNAm) at PHGDH (cg14476101) with coffee consumption and blood pressure, which may explain the mechanism underlying coffee intake and blood pressure. However, little is known about whether the coffee-related DNAm is associated with long-term changes in blood pressure in response to dietary weight-loss interventions. Hypothesis: We hypothesized that participants with varying coffee-related DNAm levels may respond differently to dietary weight-loss interventions on long-term changes in blood pressure. Methods: The current study included 669 participants with overweight/obesity, who were randomly assigned to 1 of 4 diets varying in macronutrient components. Blood DNAm levels were profiled by a high-resolution methylC-capture sequencing at baseline. The regional DNAm at PHGDH was defined as the average methylation level over CpGs within ±250 bp of cg14476101. Two-year changes in blood pressure were calculated. Linear regression models were used to examine the associations between DNAm at PHDGH and 2-year changes in blood pressure in response to dietary weight-loss interventions, adjusting for age, race, sex, body mass index, anti-hypertensive medications, and concurrent weight loss. Results: Regional DNAm at PHDGH was not associated with 2-year changes in blood pressure in the total population. We found significant interactions between regional DNAm at PHDGH and dietary protein intake on 2-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p-interaction=0.018 and 0.005, respectively). Among participants assigned to an average-protein diet (15% of energy intake), higher baseline regional DNAm at PHDGH was associated with greater reductions in SBP (beta [SE]: -9.7 [3.4], p=0.005) and DBP (beta [SE]: -6.5 [2.4], p=0.007); while no association was observed among those assigned to a high-protein diet (25% of energy intake; p=0.40 for SBP, p=0.15 for BP). Conclusion: Our data indicate that participants with a higher regional DNAm level at PHDGH benefited more in long-term improvement in blood pressure when consuming an average-protein weight-loss diet.

Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial

The SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial showed the safety but not efficacy of the Symplicity system (Medtronic, Santa Rosa, CA, USA) at 6 months follow-up in patients with treatment-resistant hypertension. This final report presents the 36-month follow-up results. SYMPLICITY HTN-3 was a single-blind, multicentre, sham-controlled, randomised clinical trial, done in 88 centres in the USA. Adults aged 18-80 years, with treatment-resistant hypertension on stable, maximally tolerated doses of three or more drugs including a diuretic, who had a seated office systolic blood pressure of 160 mm Hg or more and 24 h ambulatory systolic blood pressure of 135 mm Hg or more were randomly assigned (2:1) to receive renal artery denervation using the single electrode (Flex) catheter or a sham control. The original primary endpoint was the change in office systolic blood pressure from baseline to 6 months for the renal artery denervation group compared with the sham control group. Patients were unmasked after the primary endpoint assessment at 6 months, at which point eligible patients in the sham control group who met the inclusion criteria (office blood pressure ≥160 mm Hg, 24 h ambulatory systolic blood pressure ≥135 mm Hg, and still prescribed three or more antihypertensive medications) could cross over to receive renal artery denervation. Changes in blood pressure up to 36 months were analysed in patients in the original renal artery denervation group and sham control group, including those who underwent renal artery denervation after 6 months (crossover group) and those who did not (non-crossover group). For comparisons between the renal artery denervation and sham control groups, follow-up blood pressure values were imputed for patients in the crossover group using their most recent pre-crossover masked blood pressure value. We report long-term blood pressure changes in renal artery denervation and sham control groups, and investigate blood pressure control in both groups using time in therapeutic blood pressure range analysis. The primary safety endpoint was the incidence of all-cause mortality, end stage renal disease, significant embolic event, renal artery perforation or dissection requiring intervention, vascular complications, hospitalisation for hypertensive crisis unrelated to non-adherence to medications, or new renal artery stenosis of more than 70% within 6 months. The trial is registered with ClinicalTrials.gov, NCT01418261. From Sep 29, 2011, to May 6, 2013, 1442 patients were screened, of whom 535 (37%; 210 [39%] women and 325 [61%] men; mean age 57·9 years [SD 10·7]) were randomly assigned: 364 (68%) patients received renal artery denervation (mean age 57·9 years [10·4]) and 171 (32%) received the sham control (mean age 56·2 years [11·2]). 36-month follow-up data were available for 219 patients (original renal artery denervation group), 63 patients (crossover group), and 33 patients (non-crossover group). At 36 months, the change in office systolic blood pressure was -26·4 mm Hg (SD 25·9) in the renal artery denervation group and -5·7 mm Hg (24·4) in the sham control group (adjusted treatment difference -22·1 mm Hg [95% CI -27·2 to -17·0]; p≤0·0001). The change in 24 h ambulatory systolic blood pressure at 36 months was -15·6 mm Hg (SD 20·8) in the renal artery denervation group and -0·3 mm Hg (15·1) in the sham control group (adjusted treatment difference -16·5 mm Hg [95% CI -20·5 to -12·5]; p≤0·0001). Without imputation, the renal artery denervation group spent a significantly longer time in therapeutic blood pressure range (ie, better blood pressure control) than patients in the sham control group (18% [SD 25·0] for the renal artery denervation group vs 9% [SD 18·8] for the sham control group; p≤0·0001) despite a similar medication burden, with consistent and significant results with imputation. Rates of adverse events were similar across treatment groups, with no evidence of late-emerging complications from renal artery denervation. The rate of the composite safety endpoint to 48 months, including all-cause death, new-onset end-stage renal disease, significant embolic event resulting in end-organ damage, vascular complication, renal artery re-intervention, and hypertensive emergency was 15% (54 of 352 patients) for the renal artery denervation group, 14% (13 of 96 patients) for the crossover group, and 14% (10 of 69 patients) for the non-crossover group. This final report of the SYMPLICITY HTN-3 trial adds to the totality of evidence supporting the safety of renal artery denervation to 36 months after the procedure. From 12 months to 36 months after the procedure, patients who were originally randomly assigned to receive renal artery denervation had larger reductions in blood pressure and better blood pressure control compared with patients who received sham control. Medtronic.

Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia

Women with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal disease later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE during pregnancy and up to 2-year postpartum (PP), and in the reduced uterine perfusion pressure (RUPP) rat model of PE. Blockade of AT1-AA with a specific 7 amino acid peptide binding sequence (‘n7AAc’) improves pathophysiology observed in RUPP rats; however, the long-term effects of AT1-AA inhibition in PP is unknown. Pregnant Sprague Dawley rats were divided into three groups: normal pregnant (NP) (n = 16), RUPP (n = 15), and RUPP + ‘n7AAc’ (n = 16). Gestational day 14, RUPP surgery was performed and ‘n7AAc’ (144 μg/day) administered via osmotic minipump. At 10-week PP, mean arterial pressure (MAP), renal glomerular filtration rate (GFR) and cardiac functions, and cardiac mitochondria function were assessed. MAP was elevated PP in RUPP vs. NP (126 ± 4 vs. 116 ± 3 mmHg, p < 0.05), but was normalized in in RUPP + ‘n7AAc’ (109 ± 3 mmHg) vs. RUPP (p < 0.05). PP heart size was reduced by RUPP + ’n7AAc’ vs. RUPP rats (p < 0.05). Complex IV protein abundance and enzymatic activity, along with glutamate/malate-driven respiration (complexes I, III, and IV), were reduced in the heart of RUPP vs. NP rats which was prevented with ‘n7AAc’. AT1-AA inhibition during pregnancy not only improves blood pressure and pathophysiology of PE in rats during pregnancy, but also long-term changes in blood pressure, cardiac hypertrophy, and cardiac mitochondrial function PP.

The Association between Low Blood Pressure and Attention-Deficit Hyperactivity Disorder (ADHD) Observed in Children/Adolescents Does Not Persist into Young Adulthood. A Population-Based Ten-Year Follow-Up Study

Background: Attention-deficit hyperactivity disorder (ADHD) is one of the most common behavioral disorders in childhood and adolescence associated with relevant psychosocial impairments. The basic pathophysiology of ADHD may be related, at least partly, to a deficit in autonomic arousal processes, which not only influence core symptoms of the disorder, but may also lead to blood pressure (BP) deviations due to altered arousal regulation. Objectives: This study examined long-term changes in BP in children and adolescents with ADHD up to young adulthood. Methods: In children and adolescents aged between 7 and 17 years at baseline, we compared BP recordings in subjects with (n = 1219, 11.1%) and without (n = 9741, 88.9%) ADHD over a 10-year follow-up using data from the nationwide German Health Survey for Children and Adolescents (KiGGS). Propensity score matching was used to improve the comparability between children in the ADHD and control groups with now n = 1.190 in each group. Results: The results of these matched samples revealed that study participants with ADHD showed significantly lower systolic BP (107.6 ± 10.7 mmHg vs. 109.5 ± 10.9 mmHg, p < 0.001, Cohen’s d = 0.17) and diastolic BP (64.6 ± 7.5 mmHg vs. 65.8 ± 7.4 mmHg, p < 0.001, Cohen’s d = 0.16) at baseline. In a sensitivity analysis with a smaller (n = 272) and more stringently diagnosed ADHD group, the significant differences remained stable with somewhat higher Cohen’s d; i.e., 0.25 and 0.27, respectively. However, these differences did not persist after 10-year follow-up in a smaller matched longitudinal sub-group (ADHD n = 273; control n = 323), as subjects with and without ADHD had similar levels of systolic (123.4 ± 10.65 vs. 123.78 ± 11.1 mmHg, p = 0.675, Cohen’s d = 0.15) and diastolic BP (71.86 ± 6.84 vs. 71.85 ± 7.06 mmHg, p = 0.992, Cohen’s d = 0.16). Conclusions: At baseline, children and adolescents with ADHD had significantly lower BP (of small effect sizes) compared to the non-ADHD group, whereas this difference was no longer detectable at follow-up ten years later. These developmental alterations in BP from adolescence to early adulthood may reflect changes in the state of autonomic arousal, probably modulating the pathophysiology of ADHD.

The correlation between blood pressure response to cold pressor test and long-term blood pressure changes

Objective: The aim of the study was to investigate the correlation between blood pressure response to cold pressor test (CPT) and follow-up blood pressure after 8 years in subjects, and to evaluate the predictive value of CPT for long-term blood pressure levels. Methods: A total of 365 individuals from eight natural villages were enrolled by stratified cluster sampling from Mei County, Shaanxi Province in 2004. Baseline characteristics of subjects were collected and CPTs were conducted. Subjects were followed up in 2009 and 2012, respectively. According to the maximal change of systolic response (SR), the area under the curve (AUC) of systolic blood pressure change (AUC-SBP), the maximal change of diastolic response (DR) and the AUC of diastolic blood pressure change (AUC-DBP) in CPT, the individuals were divided into four quartile groups by above parameters, respectively: group Ⅰ (P(25)), group Ⅱ (P(50)), group Ⅲ (P(75)) and group Ⅳ (P(100)). The correlation between blood pressure response to CPT and the follow-up blood pressure was analyzed. Results: (1) There were no significant differences in baseline blood pressure levels and prevalence of hypertension among four quartile groups no matter it was grouped on SR, DR, AUC-SBP or AUC-DBP. (2) The prevalence of hypertension in each group from lowest (P(25)) to highest (P(100)) in 2012 was 25.64%, 30.67%, 38.03%, 55.74% on SR grouping (P<0.01), and 27.5%, 29.17%, 38.46%, 57.35% on AUC-SBP grouping (P<0.05), respectively. (3) There were no significant differences in the prevalence of hypertension among four groups in 2012 (P>0.05) either on DR or on AUC-DBP grouping. (4) The random effects model analysis showed that the correlation coefficient between SR, AUC-SBP and long-term systolic blood pressure increase were 1.91 (P<0.05) and 1.44 (P<0.05), respectively, and the correlation coefficient between DR, AUC-DBP and long-term diastolic blood pressure increase were 0.82 (P<0.05) and 0.78 (P>0.05), respectively. Age, male, body mass index, and fasting blood glucose were independent risk factors for long-term blood pressure elevation, and age, body mass index and fasting blood glucose positively correlated with changes in long-term blood pressure (all P<0.05). Conclusion: Individual systolic blood pressure response to CPT can be used as a predictor of long-term hypertension.

Short-Term and Long-Term Blood Pressure Changes and the Risk of All-Cause and Cardiovascular Mortality.

Background Few studies compared the effects of BP changes in short- and long-terms on all-cause mortality and CVD mortality. Methods We performed a 12.5-year follow-up study to examine the association between short- (2008 to 2010) and long-term [baseline (2004-2006) to 2010] BP changes and the risk of mortality (2010 to 2017) in the Fuxin prospective cohort study. The Cox proportional hazards model was used for this study, and the average BP was stratified according to the Seven Joint National Committee (JNC7). Results We identified 1496 (805 CVD deaths) and 2138 deaths (1222 CVD deaths) in short- and long-term study. Compared with BP maintainer, in short-term BP changes, for participants from normotension or prehypertension to hypertension, the hazards ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality were 1.948 (1.118-3.392) and 1.439 (1.218-1.700), respectively, while for participants from hypertension to prehypertension, the HRs (95% CIs) were 0.766 (0.638-0.899) for all-cause mortality and 0.729 (0.585-0.908) for CVD mortality, respectively. In long-term BP changes, for participants from normotension or prehypertension to hypertension, the HRs (95% CIs) of all-cause mortality were 1.738 (1.099-2.749) and 1.203 (1.023-1.414), and they were 2.351 (1.049-5.269) and 1.323 (1.047-1.672) for CVD mortality, respectively. In addition, the effects of short-term BP changes on all-cause and CVD mortality, measured as regression coefficients (β), were significantly greater than those in long-term change (all P<0.05). Conclusions Our study emphasizes that short-term changes in BP have a greater impact on all-cause and CVD mortality than long-term changes and assess the cut-off value of the changes in blood pressure elevation.

Short-term blood pressure changes have a more strong impact on stroke and its subtypes than long-term blood pressure changes.

BackgroundElevated blood pressure (BP) is closely related to stroke and its subtypes. However, different time periods changes in BP may result in differential risk of stroke.HypothesisShort‐term blood pressure changes have a more strong impact on stroke and its subtypes than long‐term blood pressure changes.MethodsWe designed the study on the effects of short‐ (2008‐2010) and long‐term (2004‐2010) BP changes on stroke events (2011‐2017), including 22 842 and 28 456 subjects, respectively. The difference in β coefficients between short‐ and long‐term BP changes on the effects of stroke were examined using the Fisher Z test.ResultsDuring a median 12.5‐year follow‐up period, 1014 and 1505 strokes occurred in short‐ and long‐term groups. In short‐term group, going from prehypertension to hypertension, the risk of stroke events increased (stroke: hazard ratio [HR] = 1.537 [1.248‐1.894], ischemic stroke: 1.456 [1.134‐1.870] and hemorrhagic stroke: 1.630 [1.099‐2.415]); going from hypertension to prehypertension, the risk of stroke events decreased (stroke:0.757 [0.619‐0.927] and hemorrhagic stroke:0.569 [0.388‐0.835]). Similarly, in long‐term group, going from prehypertension to hypertension, individuals had an increased risk of stroke (1.291, 1.062‐1.569) and hemorrhagic stroke (1.818, 1.261‐2.623); going from hypertension to prehypertension, participants had a decreased risk of stroke (0.825, 0.707‐0.963) and hemorrhagic stroke (0.777, 0.575‐0.949). Furthermore, the effects of BP changes during short‐term period on stroke events were greater than that in long‐term period.ConclusionsShort‐ and long‐terms BP changes were both associated with the risk of stroke events. Furthermore, short‐term BP changes had a stronger impact than did long‐term changes on risk of stroke events.

Association between long-term blood pressure change and the incidence of cardiovascular diseases: a population-based cohort study

Objective: To explore the association between long-term changes in blood pressure (BP) levels and the incidence of cardiovascular diseases (CVD). Methods: A total of 5 752 participants, who participated baseline examination in 1992-1993 and re-examination in 2007, were followed up till December 31, 2013 according to the study protocol of the Chinese Multi-provincial Cohort Study. Participants were stratified by baseline BP and re-examination BP and cross-combined into 9 subgroups. The 20-year incidence of acute cardiovascular events, acute coronary heart disease (CHD) and acute stroke events were analyzed and association between disease incidence and 15-year changes in BP were determined using the competing risk regression model. Results: (1) There were 523 CVD events (170 CHD, 373 stroke) during the 20 years follow up. The number of participants with baseline systolic blood pressure (SBP)/diastolic blood pressure (DBP) of <130/80 mmHg (1 mmHg=0.133 kPa), 130-139/80-89 mmHg, and hypertension were 2 892 (50.3%), 1 328 (23.1%) and 1 532 (26.6%), respectively. (2) Among participants with baseline SBP of 130-139 mmHg or DBP of 80-89 mmHg, 870 (65.5%) progressed to hypertension and 279 (21.0%) maintained at the same stratum over a 15-year follow up period. (3) After adjustment for age, sex, body mass index, smoking status, diabetes, total cholesterol, and high-density lipoprotein cholesterol at baseline, participants maintained SBP/DBP at 130-139/80-89 mmHg had a higher risk of developing acute cardiovascular events, CHD and stroke with the hazard ratios (HR) and 95% confidence interval (95%CI) of 2.04 (1.16, 3.57), 3.29 (1.30, 8.35) and 1.63 (0.80, 3.33), compared with those who maintained their SBP < 130 mmHg and DBP <80 mmHg. Participants whose BP increased from 130-139/80-89 mmHg to hypertension over the follow up period had 2.81-fold (1.84, 4.29), 3.17-fold (1.43, 7.03) and 2.71-fold (1.65, 4.44) higher risk for the incidence of acute cardiovascular events, CHD, and stroke, respectively, compared with participants who maintained their SBP <130 mmHg and DBP <80 mmHg. Conclusions: Participants with SBP/DBP of 130-139/80-89 mmHg have a high long-term risk for progression to hypertension. Sustained exposure to SBP/DBP of 130-139/80-89 mmHg or higher increases the risk of CVD incidence, and our results highlight the importance of early prevention for participants with this BP stratum.

Ambulatory blood pressure monitoring in living kidney donors: What changes in 10years?

In renal transplantation, living donations have more significant benefits compared to cadaveric donations. However, a probable increase in blood pressure following donation should also be kept in mind. In this study, we investigated the long-term changes in blood pressure in living kidney donors using ambulatory blood pressure monitoring and we explored the e-GFR and albuminuria/proteinuria measurements at 3 time points. Twenty-eight living kidney donors and 39 healthy individuals were evaluated and compared at the baseline and later at the 10th year. At the 10th year, creatinine levels were higher and eGFR levels were lower in the donors, whereas the systolic and diastolic measurements of the donors and controls and the prevalence of nondipping in the donors and controls were similar. Our study may be underpowered due to its small population size. However, our results at the 10th year follow-up indicated that the risk of hypertension might not seem to have increased in the well-selected donors. In addition, the majority of our donors had preserved their GFR values. Therefore, we can suggest that living kidney donation appears to be safe in well-selected patients over a 10-year time frame.

Cardiovascular risk factors and carotid intima media thickness in young adults born small for gestational age after cessation of growth hormone treatment: a 5-year longitudinal study

Growth hormone treatment reduces blood pressure and lipid concentrations. We assessed long-term changes in blood pressure, lipid concentrations, and carotid intima media thickness over a 5-year period after cessation of growth hormone treatment in adults born small for gestational age. We did a longitudinal observational study at a medical centre in the Netherlands between April 1, 2004, and April 1, 2016. We included adults born small for gestational age who were treated with growth hormone (1 mg/m2 per day); treatment started during childhood until adult height. Participants were evaluated at cessation of treatment, and 6 months, 2 years, and 5 years later. We compared cardiovascular risk factors with untreated controls from the PROGRAM study. We included 199 participants born small for gestational age and treated with growth hormone along with 285 controls: 51 untreated short adults born small for gestational age, 92 untreated adults born small for gestational age with spontaneous catch-up growth, and 142 adults born appropriate for gestational age. In the 6 months after treatment cessation, systolic blood pressure increased temporarily from 113·00 mm Hg (95% CI 111·18-114·82) to 116·92 mm Hg (115·07 to 118·77; p<0·001) and diastolic blood pressure increased temporarily from 62·19 mm Hg (60·99-63·38) to 66·51 mm Hg (65·14-67·89; p<0·001). At 5 years after treatment cessation, mean systolic blood pressure was 109·2 mm Hg (105·5-113·0) and mean diastolic blood pressure was 63·4 mm Hg (60·9-65·9), similar to the values at cessation. Lipid concentrations were non-significantly higher 5 years after treatment cessation (p values 0·09-0·21) than at treatment cessation. Cessation of growth hormone had no effect on carotid intima media thickness. At 5 years after cessation, total cholesterol was lower in adults treated with growth hormone (mean 4·21 mmol/L, 95% CI 4·04-4·38) than in untreated short adults born small for gestational age (4·66 mmol/L, 4·42-4·92; p=0·0030), as was mean LDL cholesterol (2·28 mmol/L, 2·14-2·43 vs 2·85 mmol/L, 2·62-3·10; p<0·0001); blood pressure and carotid intima media thickness did not differ between these two groups (p values >0·12). At 5 years after cessation, systolic blood pressure, diastolic blood pressure, lipid concentrations, and carotid intima media thickness of adults treated with growth hormone were not different to those in adults born small for gestational age who had spontaneous catch-up growth or adults born appropriate for gestational age. Long-term growth hormone treatment in children born small for gestational age has no unfavourable effects on cardiovascular health in early adulthood and improves lipid profiles. Novo Nordisk (Netherlands).

Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure.

Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of protein levels encoded by candidate genes for subsequent cardiovascular disease was investigated. Eight transcripts (CRIP1, MYADM, TIPARP, TSC22D3, CEBPA, F12, LMNA, and TPPP3) were identified jointly accounting for up to 13% (95% confidence interval, 8.7-16.2) of BP variability. Changes in CRIP1, MYADM, TIPARP, LMNA, TSC22D3, CEBPA, and TPPP3 expression associated with BP changes-among these, CRIP1 gene expression was additionally correlated to measures of cardiac hypertrophy. Assessment of circulating CRIP1 (cystein-rich protein 1) levels as biomarkers showed a strong association with increased risk for incident stroke (hazard ratio, 1.06; 95% confidence interval, 1.03-1.09; P=5.0×10-5). Our comprehensive analysis of global gene expression highlights 8 novel transcripts significantly associated with BP, providing a link between gene expression and BP. Translational approaches further established evidence for the potential use of CRIP1 as emerging disease-related biomarker.

Prognostic value of long-term blood pressure changes in patients with chronic heart failure.

Chronic heart failure (CHF) is the final stage of many heart diseases. To improve outcomes, important risk factors for adverse clinical events in the CHF population need to be identified. The aim of the present study was to delineate the influence of long-term blood pressure (BP) changes on prognosis and mortality in a real-world cohort of CHF patients. This is a retrospective longitudinal analysis. Repeated office BP measurements were scheduled during follow-up visits every 3-6 months. The primary endpoint was time to death or heart transplantation (HTx). A Cox regression with time-dependent strata was used to analyse the effect of systolic BP (SBP) values and its change during follow-up on the primary endpoint. A total of 927 patients presented with a median survival of 7.7 [95% confidence interval (CI) 6.6-9.8] years. During follow-up, 220 patients died and 70 patients underwent HTx. The BP stratum with the most stable values showed the best survival. Blood pressure changes with an increase or decrease greater than ±10 mmHg per year led to a significantly worse outcome [hazard ratio (HR) 1.8 and 2.0, respectively]. The stratum with the lowest SBP levels (<90 mmHg) had the highest mortality. Multiple regression analysis showed a HR factor of 17 (95% CI 9.7-29) in comparison with the stratum with SBP ≥130 mmHg. Low SBP (<90 mmHg) and pronounced long-term changes in SBP were associated with poor survival in patients with CHF. Additional prospective studies are warranted to further specify optimal BP targets in patients with CHF.

Long-Term Effect of the Type of Carotid Endarterectomy on Blood Pressure

The dissection of the carotid sinus nerve in eversion carotid endarterectomy (eCEA) has been hypothesized to cause an increase in postoperative blood pressure (BP). The objective of this study is to evaluate the effect of eCEA on BP and changes in BP medications over the course of year-long follow-up after eCEA compared with longitudinal incision carotid endarterectomy patch angioplasty (pCEA). A retrospective review of patients who underwent CEA between July 1, 2009 and June 30, 2014 in the Vascular Surgery Department at The University of Iowa Hospital and Clinics was conducted. Demographics, comorbidities, BP, and number, dosage, and type of antihypertensive medications were collected preoperatively, at 30 days, and at 12 months. The differences in BP and medications between pCEA and eCEA patients were compared. Demographic data and comorbidities were compared using t-tests and chi-squared analysis. Differences in BP and medication dosages were analyzed using multivariate analysis of variance. In total, 363 CEA procedures were performed during the study period, of which 275 procedures were included in the final analysis. Thirty percent of the patients underwent eCEA. Fifty-four percent of the patients who underwent eCEA and 60% of the patients who underwent pCEA were symptomatic. Thirty-day mortality was 1.4% and 12-month mortality was 6.4% for the entire population. No postoperative neurologic deficits, including stroke, were observed. Analysis of BP did not yield a significant difference among preoperative, 30-day, and 12-month follow-up measurements (P=0.893). There was no significant change to the number and total daily dose of BP medications preoperatively, at 30days, or at 12months. There is no statistical difference in mortality, morbidity, and patency rates at 30days and 12months between pCEA and eCEA. eCEA is also not associated with long-term BP changes compared with pCEA.

Intake of low sodium salt substitute for 3 years attenuates the increase in blood pressure in a rural population of North China — A randomized controlled trial

BackgroundLowering salt intake is one of the successful and cost-effective methods to reduce blood pressure (BP). In this randomized controlled study, we investigated the effects of a 3-year substitution of table salt with a low-sodium salt substitute in a rural population of North China. MethodsSubjects from 200 families residing in five villages in Liaoning, North China were registered in this study and randomly divided into two groups: normal salt (100% sodium chloride) and low salt substitute (65% NaCl, 25% KCl, 10% MgSO4). We compared the effects of the low-sodium salt substitute and normal salt on differences in BP from baseline to various follow-up time points during this 3-year study period. We also examined several factors that may affect the long-term changes in BP. Hypertension was defined per World Health Organization guidelines as BP≥140/90mmHg. ResultsThe low sodium substitute significantly reduced the increase in both systolic and diastolic BP compared with the regular salt (P=0.000). Also, the population aged 40–70years showed most beneficial response to the salt substitute compared with those aged <40 or >70years. The low salt substitute had similar beneficial effects in both males and females. In addition, the salt type consumed and body mass index significantly affected the change in BP. ConclusionUse of the salt substitute significantly reduces the increase in BP over a long term, and thus, the salt substitute can be used as a replacement for regular salt in the daily diet to prevent/diminish the incidence of hypertension.

Renal Dysfunction, Rather Than Nonrenal Vascular Dysfunction, Mediates Salt-Induced Hypertension.

Chronic excess salt intake increases the risk for hypertension and moderation of salt intake is an important strategy for prevention of cardiovascular and kidney disease, especially in salt-sensitive subjects. Although short-term blood pressure (BP) responses to high salt intake over several days are highly variable, chronic high salt intake worsens BP salt-sensitivity. Aging, diabetes, hypertension, and various acquired and genetic kidney disorders also exacerbate salt-sensitivity of BP. Kidney dysfunction, characterized by impaired pressure natriuresis, has been demonstrated in all forms of experimental and human genetic or acquired salt-sensitive hypertension studied thus far. Abnormalities of kidney function that directly or indirectly increase NaCl reabsorption, decrease glomerular capillary filtration coefficient, or cause nephron injury/loss exacerbate BP salt-sensitivity. In most cases, salt-sensitive hypertension is effectively treated with drugs that increase glomerular filtration rate or reduce renal NaCl reabsorption (e.g. diuretics, renin-angiotensin-aldosterone system blockers). Increased vascular resistance may occur concomitantly or secondarily to kidney dysfunction and increased BP in salt-sensitive hypertension. However, primary increases in non-renal vascular resistance have not been shown to cause salt-sensitive hypertension or long-term changes in BP in the absence of impaired renal-pressure natriuresis. The mechanisms responsible for increased total peripheral resistance (TPR) during high salt intake in salt-sensitive subjects are not fully understood but likely involve pressure-dependent and/or flow-dependent autoregulation in peripheral tissues as well as neurohormonal factors that occur concomitantly with kidney dysfunction. Physiological studies have demonstrated that increased BP almost invariably initiates secondary pressure-dependent functional and structural vascular changes that increase TPR.

Long-Term Changes in Blood Pressure After Pediatric Kidney Transplantation.

Hypertension presents high prevalence rates following kidney transplantation (Tx). The aims of the present study were to investigate the prevalence and possible risk factors for hypertension and blood pressure (BP) control over time after pediatric kidney Tx, as well as to assess possible effects of hypertension on graft survival. We reviewed the medical records of all pediatric kidney recipients followed up in our pediatric nephrology department. Hypertension was defined as systolic and/or diastolic BP greater than the 95th percentile for age and sex, or as being on antihypertensive medication. BP control was defined as normotension while on antihypertensive medication. The study population included 74 pediatric kidney recipients (median age 11 years). The prevalence of hypertension was found 77% before Tx, 82.4%, 71.7%, and 61% at 1, 5, and 10 years after Tx, respectively. Deceased donor Tx and pre-transplant hypertension on antihypertensive medication were significant risk factors for hypertension after kidney Tx over the follow-up period. BP control among patients on antihypertensive treatment was 16.7% before Tx, 43.8%, 66.7%, and 42.9% at 1, 5, and 10 years post-Tx, respectively. Hypertensive patients at 10 years post-Tx had 8.079 times higher hazard of graft loss compared to normotensives (95% CI 1.561-41.807, P < 0.05). Hypertension remains a frequent complication in pediatric kidney recipients even years after kidney Tx. BP control by antihypertensive treatment is unsatisfactory in about half of the patients. The adverse effects of hypertension on graft survival may appear in the long-term.

Patient controlled epidural therapy in labouring women

The dissection of the carotid sinus nerve in eversion carotid endarterectomy (eCEA) has been hypothesized to cause an increase in postoperative blood pressure (BP). The objective of this study is to evaluate the effect of eCEA on BP and changes in BP medications over the course of year-long follow-up after eCEA compared with longitudinal incision carotid endarterectomy patch angioplasty (pCEA).A retrospective review of patients who underwent CEA between July 1, 2009 and June 30, 2014 in the Vascular Surgery Department at The University of Iowa Hospital and Clinics was conducted. Demographics, comorbidities, BP, and number, dosage, and type of antihypertensive medications were collected preoperatively, at 30 days, and at 12 months. The differences in BP and medications between pCEA and eCEA patients were compared. Demographic data and comorbidities were compared using t-tests and chi-squared analysis. Differences in BP and medication dosages were analyzed using multivariate analysis of variance.In total, 363 CEA procedures were performed during the study period, of which 275 procedures were included in the final analysis. Thirty percent of the patients underwent eCEA. Fifty-four percent of the patients who underwent eCEA and 60% of the patients who underwent pCEA were symptomatic. Thirty-day mortality was 1.4% and 12-month mortality was 6.4% for the entire population. No postoperative neurologic deficits, including stroke, were observed. Analysis of BP did not yield a significant difference among preoperative, 30-day, and 12-month follow-up measurements (P = 0.893). There was no significant change to the number and total daily dose of BP medications preoperatively, at 30 days, or at 12 months.There is no statistical difference in mortality, morbidity, and patency rates at 30 days and 12 months between pCEA and eCEA. eCEA is also not associated with long-term BP changes compared with pCEA.

Update on the Guytonian view of hypertension.

Dr Arthur Guyton hypothesized that the capacity of the kidney to excrete sodium ultimately dictates long-term changes in blood pressure. This model has had a profound influence on our understanding of blood pressure regulation. The goal of this article is to review a selection of classic studies and highlight more recent molecular studies supporting or refuting the Guyton model of blood pressure regulation. Molecular characterizations of human disorders of sodium homeostasis and blood pressure, and phenotypic analysis of transgenic mouse models, strongly support the Guytonian view that the kidney plays a central role in blood pressure control. However, recent studies also support the view that primary changes in the vasculature and nervous system significantly contribute to long-term changes in blood pressure. The findings from provocative studies, particularly those that demonstrate how primary changes in the vasculature alter blood pressure without affecting renal sodium handling, challenge the Guyton model and need to be reconciled with the basic tenets of this model. Future characterization of these exceptions to the Guyton model will be critical in gaining a more complete understanding of the physiology of blood pressure regulation. This path of discovery will undoubtedly lead to new approaches for the diagnosis and treatment of hypertension.