Hg Higher Systolic Blood Pressure Research Articles

Association of Antibodies to Citrullinated Protein Antigens with Blood Pressure in First-Degree Relatives of Rheumatoid Arthritis Patients: The Studies of the Etiology of Rheumatoid Arthritis

Background: Hypertension is more common in patients with rheumatoid arthritis (RA) than in the general population. It is unknown whether hypertension is due to RA-related medications or the disease itself. Therefore, we sought to investigate associations between RA-related autoantibodies, specifically antibodies to citrullinated protein antigens (ACPA) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in first-degree relatives of RA patients, who were free of RA and RA-related medications. We hypothesized that a greater number of detectable ACPA would be associated with high SBP and DBP, independent of other risk factors in these first-degree relatives. Methods: We evaluated associations between ACPA and SBP and DBP in a cross-sectional study of 72 first-degree relatives (defined as parent, child, or sibling) of RA patients. Fifteen ACPA were measured using a Bio-Plex bead-based assay; each was dichotomized as positive/negative based on pre-specified cut-points. Analysis of covariance was used to evaluate associations between ACPA positivity and SBP and DBP, adjusting for age, sex, race, body mass index (BMI), pack-years of smoking, high sensitivity C-reactive protein (hsCRP), and current use of anti-hypertensive medications. Results: Average age was 51 and 69% were women. Mean SBP was 119 ± 18 and DBP was 74 ± 9 mm Hg. Thirty-three (46%) first-degree relatives were positive for ≥1 ACPA; and were younger, had lower BMI, more pack-years of smoking, and higher hsCRP concentrations compared to ACPA negative first-degree relatives. For each additional positive ACPA, SBP was 0.98 ± 0.5 mm Hg (p = 0.05) higher, and DBP was 0.66 ± 0.3 mm Hg (p = 0.04) higher. Anti-cit-fibrinogen A (211–230) positive and anti-cit-filaggrin positive first-degree relatives had 11.5 and 13.9 mm Hg higher SBP (p = 0.02) respectively. Anti-cit-clusterin, cit-filaggrin, and cit-vimentin positive first-degree relatives had 7–8 mm Hg higher DBP (p = 0.03, 0.05, 0.05 respectively), compared to being negative for these individual ACPA. Consistent with associations between ACPA, SBP, and DBP, anti-cyclic citrullinated peptides (anti-CCP2) positive first-degree relatives had 16.4± (p = 0.03) higher SBP and 12.1± mm Hg (p = 0.01) higher DBP than anti-CCP2 negative first-degree relatives. Conclusion: In first-degree relatives without RA, ACPA positivity is associated with higher SBP and DBP. Subclinical autoimmune processes and ACPA may play a role in the vascular changes potentially leading to hypertension prior to RA onset.

Phenotypic Consequences of a Genetic Predisposition to Enhanced Nitric Oxide Signaling.

Nitric oxide signaling plays a key role in the regulation of vascular tone and platelet activation. Here, we seek to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on risk for cardiovascular diseases, thus informing the potential utility of pharmacological stimulation of the nitric oxide pathway as a therapeutic strategy. We analyzed the association of common and rare genetic variants in 2 genes that mediate nitric oxide signaling (Nitric Oxide Synthase 3 [NOS3] and Guanylate Cyclase 1, Soluble, Alpha 3 [GUCY1A3]) with a range of human phenotypes. We selected 2 common variants (rs3918226 in NOS3 and rs7692387 in GUCY1A3) known to associate with increased NOS3 and GUCY1A3 expression and reduced mean arterial pressure, combined them into a genetic score, and standardized this exposure to a 5 mm Hg reduction in mean arterial pressure. Using individual-level data from 335 464 participants in the UK Biobank and summary association results from 7 large-scale genome-wide association studies, we examined the effect of this nitric oxide signaling score on cardiometabolic and other diseases. We also examined whether rare loss-of-function mutations in NOS3 and GUCY1A3 were associated with coronary heart disease using gene sequencing data from the Myocardial Infarction Genetics Consortium (n=27 815). A genetic predisposition to enhanced nitric oxide signaling was associated with reduced risks of coronary heart disease (odds ratio, 0.37; 95% confidence interval [CI], 0.31-0.45; P=5.5*10-26], peripheral arterial disease (odds ratio 0.42; 95% CI, 0.26-0.68; P=0.0005), and stroke (odds ratio, 0.53; 95% CI, 0.37-0.76; P=0.0006). In a mediation analysis, the effect of the genetic score on decreased coronary heart disease risk extended beyond its effect on blood pressure. Conversely, rare variants that inactivate the NOS3 or GUCY1A3 genes were associated with a 23 mm Hg higher systolic blood pressure (95% CI, 12-34; P=5.6*10-5) and a 3-fold higher risk of coronary heart disease (odds ratio, 3.03; 95% CI, 1.29-7.12; P=0.01). A genetic predisposition to enhanced nitric oxide signaling is associated with reduced risks of coronary heart disease, peripheral arterial disease, and stroke. Pharmacological stimulation of nitric oxide signaling may prove useful in the prevention or treatment of cardiovascular disease.

Vitamin D, Hypertension, and Ischemic Stroke in 116 655 Individuals From the General Population: A Genetic Study.

Observational studies indicate that low concentrations of plasma 25-hydroxyvitamin D (25(OH)D) are associated with high blood pressure, hypertension, and ischemic stroke. However, whether these associations are causal remain unknown. A total of 116 655 white individuals of Danish descent from the general population were genotyped for genetic variants in DHCR7 and CYP2R1 affecting plasma 25(OH)D concentrations; 35 517 had plasma 25(OH)D measurements. Primary outcomes were blood pressure, hypertension, and ischemic stroke. Median follow-up for incident ischemic stroke was 9.3 years (range, 1 day-33.6 years). DHCR7/CYP2R1 allele score was as expected associated with lower 25(OH)D concentration (F=328 and R2=1.0%). A genetically determined 10 nmol/L lower 25(OH)D concentration was associated with a 0.68 (95% confidence interval [CI], 0.20-1.17) mm Hg higher systolic blood pressure and a 0.36 (95% CI, 0.08-0.63) mm Hg higher diastolic blood pressure with corresponding observational estimates of 0.58 (95% CI, 0.50-0.68) and 0.40 (95% CI, 0.35-0.45) mm Hg. The odds ratio for hypertension was 1.02 (95% CI, 0.97-1.08) for a genetically determined 10 nmol/L lower 25(OH)D with a corresponding observational odds ratio of 1.06 (95% CI, 1.05-1.07). The odds ratio for ischemic stroke was 0.98 (95% CI, 0.86-1.13) for a genetically determined 10 nmol/L decrease in 25(OH)D with a corresponding observational odds ratio of 1.03 (95% CI, 1.01-1.05). Genetic and observational low 25(OH)D concentrations were associated with higher blood pressure, as well as with hypertension consistent with causal relationships. Because observational but not genetic low 25(OH)D concentration was associated with ischemic stroke, and as the CIs overlapped, we can neither support nor exclude a causal relationship.

Baseline Blood Pressure Effect on the Benefit and Safety of Intra-Arterial Treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands).

High blood pressure (BP) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke. Whether BP influences the benefit or safety of intra-arterial treatment (IAT) is not known. We aimed to assess the relation of BP with functional outcome, occurrence of symptomatic intracranial hemorrhage and effect of IAT. This is a post hoc analysis of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). BP was measured at baseline, before IAT or stroke unit admission. We estimated the association of baseline BP with the score on the modified Rankin Scale at 90 days and safety parameters with ordinal and logistic regression analysis. Effect of BP on the effect of IAT was tested with multiplicative interaction terms. Systolic BP (SBP) had the best correlation with functional outcome. This correlation was U-shaped; both low and high baseline SBP were associated with poor functional outcome. Higher SBP was associated with symptomatic intracranial hemorrhage (adjusted odds ratio, 1.25 for every 10 mm Hg higher SBP [95% confidence interval, 1.09-1.44]). Between SBP and IAT, there was no interaction for functional outcome, symptomatic intracranial hemorrhage, or other safety parameters; the absolute benefit of IAT was evident for the whole SBP range. The same was found for diastolic BP. BP does not affect the benefit or safety of IAT in patients with acute ischemic stroke caused by proximal intracranial vessel occlusion. Our data provide no arguments to withhold or delay IAT based on BP. URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758.

Hypertension in Pregnancy and Offspring Cardiovascular Risk in Young Adulthood: Prospective and Sibling Studies in the HUNT Study (Nord-Trøndelag Health Study) in Norway.

Women with hypertensive disorders in pregnancy are at increased lifetime risk for cardiovascular disease. We examined the offspring's cardiovascular risk profile in young adulthood and their siblings' cardiovascular risk profile. From the HUNT study (Nord-Trøndelag Health Study) in Norway, 15 778 participants (mean age: 29 years), including 210 sibling groups, were linked to information from the Medical Birth Registry of Norway. Blood pressure, anthropometry, serum lipids, and C-reactive protein were assessed. Seven hundred and six participants were born after exposure to maternal hypertension in pregnancy: 336 mothers had gestational hypertension, 343 had term preeclampsia, and 27 had preterm preeclampsia. Offspring whose mothers had hypertension in pregnancy had 2.7 (95% confidence interval, 1.8-3.5) mm Hg higher systolic blood pressure, 1.5 (0.9-2.1) mm Hg higher diastolic blood pressure, 0.66 (0.31-1.01) kg/m2 higher body mass index, and 1.49 (0.65-2.33) cm wider waist circumference, compared with offspring of normotensive pregnancies. Similar differences were observed for gestational hypertension and term preeclampsia. Term preeclampsia was also associated with higher concentrations of non-high-density lipoprotein cholesterol (0.14 mmol/L, 0.03-0.25) and triglycerides (0.13 mmol/L, 0.06-0.21). Siblings born after a normotensive pregnancy had nearly identical risk factor levels as siblings born after maternal hypertension. Offspring born after maternal hypertension in pregnancy have a more adverse cardiovascular risk profile in young adulthood than offspring of normotensive pregnancies. Their siblings, born after a normotensive pregnancy, have a similar risk profile, suggesting that shared genes or lifestyle may account for the association, rather than an intrauterine effect. All children of mothers who have experienced hypertension in pregnancy may be at increased lifetime risk of cardiovascular disease.

Adiposity and Blood Pressure in 110 000 Mexican Adults.

Previous studies have reached differing conclusions about the importance of general versus central markers of adiposity to blood pressure, leading to suggestions that population-specific adiposity thresholds may be needed. We examined the relevance of adiposity to blood pressure among 111 911 men and women who, when recruited into the Mexico City Prospective Study, were aged 35 to 89 years, had no chronic disease, and were not taking antihypertensives. Linear regression was used to estimate the effects on systolic and diastolic blood pressure of 2 markers of general adiposity (body mass index and height-adjusted weight) and 4 markers of central adiposity (waist circumference, hip circumference, waist:hip ratio, and waist:height ratio), adjusted for relevant confounders. Mean (SD) adiposity levels were: body mass index (28.7±4.5 kg/m2), height-adjusted weight (70.2±11.2 kg), waist circumference (93.3±10.6 cm), hip circumference (104.0±9.0 cm), waist:hip ratio (0.90±0.06), and waist:height ratio (0.60±0.07). Associations with blood pressure were linear with no threshold levels below which lower general or central adiposity was not associated with lower blood pressure. On average, each 1 SD higher measured adiposity marker was associated with a 3 mm Hg higher systolic blood pressure and 2 mm Hg higher diastolic blood pressure (SEs <0.1 mm Hg), but for the waist:hip ratio, associations were only approximately half as strong. General adiposity associations were independent of central adiposity, but central adiposity associations were substantially reduced by adjustment for general adiposity. Findings were similar for men and women. In Mexican adults, often overweight or obese, markers of general adiposity were stronger independent predictors of blood pressure than measured markers of central adiposity, with no threshold effects.

Genetic Association of Waist-to-Hip Ratio With Cardiometabolic Traits, Type 2 Diabetes, and Coronary Heart Disease

In observational studies, abdominal adiposity has been associated with type 2 diabetes and coronary heart disease (CHD). Whether these associations represent causal relationships remains uncertain. To test the association of a polygenic risk score for waist-to-hip ratio (WHR) adjusted for body mass index (BMI), a measure of abdominal adiposity, with type 2 diabetes and CHD through the potential intermediates of blood lipids, blood pressure, and glycemic phenotypes. A polygenic risk score for WHR adjusted for BMI, a measure of genetic predisposition to abdominal adiposity, was constructed with 48 single-nucleotide polymorphisms. The association of this score with cardiometabolic traits, type 2 diabetes, and CHD was tested in a mendelian randomization analysis that combined case-control and cross-sectional data sets. Estimates for cardiometabolic traits were based on a combined data set consisting of summary results from 4 genome-wide association studies conducted from 2007 to 2015, including up to 322 154 participants, as well as individual-level, cross-sectional data from the UK Biobank collected from 2007-2011, including 111 986 individuals. Estimates for type 2 diabetes and CHD were derived from summary statistics of 2 separate genome-wide association studies conducted from 2007 to 2015 and including 149 821 individuals and 184 305 individuals, respectively, combined with individual-level data from the UK Biobank. Genetic predisposition to increased WHR adjusted for BMI. Type 2 diabetes and CHD. Among 111 986 individuals in the UK Biobank, the mean age was 57 (SD, 8) years, 58 845 participants (52.5%) were women, and mean WHR was 0.875. Analysis of summary-level genome-wide association study results and individual-level UK Biobank data demonstrated that a 1-SD increase in WHR adjusted for BMI mediated by the polygenic risk score was associated with 27-mg/dL higher triglyceride levels, 4.1-mg/dL higher 2-hour glucose levels, and 2.1-mm Hg higher systolic blood pressure (each P < .001). A 1-SD genetic increase in WHR adjusted for BMI was also associated with a higher risk of type 2 diabetes (odds ratio, 1.77 [95% CI, 1.57-2.00]; absolute risk increase per 1000 participant-years, 6.0 [95% CI, CI, 4.4-7.8]; number of participants with type 2 diabetes outcome, 40 530) and CHD (odds ratio, 1.46 [95% CI, 1.32-1.62]; absolute risk increase per 1000 participant-years, 1.8 [95% CI, 1.3-2.4]; number of participants with CHD outcome, 66 440). A genetic predisposition to higher waist-to-hip ratio adjusted for body mass index was associated with increased risk of type 2 diabetes and coronary heart disease. These results provide evidence supportive of a causal association between abdominal adiposity and these outcomes.

Abstract 113: Adherence to Antihypertensive Medication in the Jackson Heart Study (JHS)

Objectives: Adherence to antihypertensive medications is associated with increased blood pressure (BP) control and reduced cardiovascular disease and mortality. The Jackson Heart Study (JHS) is a longitudinal study of 5,301 adults recruited from the general population of the Jackson, Mississippi area designed to evaluate cardiovascular disease in African Americans. The goal of the current analysis was to develop a measure of adherence to antihypertensive medication from available JHS data to facilitate future research in this sample. Methods: JHS participants were asked to bring in all medications taken in the prior two weeks to the baseline interview and were asked if they had taken each medication in the past 24 hours. Non-adherence was defined as not taking all antihypertensive medications in the past 24 hours. The mean of two clinic BP measurements taken one minute apart with a Hawksley random zero sphygmomanometer was used for this analysis. The associations between non-adherence and systolic/diastolic BP and uncontrolled BP (systolic/diastolic BP ≥ 140/90 mm Hg) were examined using linear and Poisson regression. Analyses were adjusted for age, sex, smoking, years of education, income, cohabitation, diabetes, depressive symptoms, and weekly stress symptoms. Results: Of the 5,301 JHS participants, 2,415 who reported current use of antihypertensive medication and had valid clinic BP and 24-hour adherence data were included. The mean age was 54.9 (SD 12.9) years and 68.7% (n=1,660) were female. Overall, 25.3% of participants (n=612) were non-adherent to their antihypertensive medication. For adherent and non-adherent participants, the mean systolic BP was 130.0 (SD 17.2) and 135.2 (SD 19.8) mm Hg, respectively ( P &lt;0.001), and the mean diastolic BP was 78.7 (SD 10.6) and 79.4 (SD 10.9) mm Hg, respectively ( P =0.15). After multivariable adjustment and compared to their adherent counterparts, non-adherent participants had 4.6 (SD 0.8) mm Hg higher systolic BP ( P &lt;.001) and 1.1 (SD 0.4) mm Hg higher diastolic BP ( P =.01). The prevalence of uncontrolled BP was 31.3% among adherent participants and 41.7% among non-adherent participants. After multivariable adjustment, non-adherent participants were 1.28 times more likely to have uncontrolled BP (95% CI:1.14-1.43; P &lt;.001). Conclusions: These findings suggest that 24-hour adherence to antihypertensive medications is a viable measure of medication adherence in the JHS. Implications: Evaluatingmedication adherence in patients with hypertension is important butchallenging. Valid and reliable self-report measures are needed when objectivemeasures are unavailable. If validated in future research, 24-hour adherence to antihypertensive medications may provide a parsimonious way of assessing medication adherence in epidemiological studies.

Clinical Implications

HomeHypertensionVol. 67, No. 2Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Feb 2016https://doi.org/10.1161/HYPERTENSIONAHA.115.06955Hypertension. 2016;67:237Early Growth and Midchildhood Blood Pressure (p 301)Download figureDownload PowerPointIn recent years, the prevalence of hypertension and prehypertension, conditions previously confined to adult populations, increased among children and adolescents. Considering that high blood pressure (BP) in early life is a strong risk factor for adult hypertension, identifying modifiable determinants of elevated BP as early as possible in the life course could translate into new preventive strategies. In a study of 957 participants of Project Viva, a US prebirth cohort, we investigated the associations of adiposity gain (change in body mass index z score) and linear growth (change in length or height z score) during 4 early-life age intervals (birth to 6 months, 6 months to 1 year, 1–2 years, and 2–3 years) with BP in midchildhood (age range, 6–10 years). We found that each additional z score gain in body mass index during birth to 6 months and 2 to 3 years corresponded with 0.81 (95% confidence interval, 0.15–1.46) and 1.61 (95% confidence interval, 0.33–2.89) mm Hg higher systolic BP, respectively. Length/height gain was unrelated to midchildhood BP, nor did any association of early growth with BP differ by birth size. Our findings suggest that faster adiposity gain during the first 6 postnatal months and in the preschool years leads to higher BP in midchildhood, regardless of size at birth. Strategies to reduce accrual of adiposity during early life may reduce midchildhood BP, with the potential to reduce risk of hypertension and cardiovascular disease in adulthood.Renal Denervation Versus Pharmacotherapy (p 397)Catheter-based renal denervation (RDN) has been considered as a new hope for patients with resistant hypertension and spread worldwide after the first studies were published in 2011. However, the first randomized controlled studies appeared only at the beginning of 2014 and cast some doubts on the real antihypertensive effect of RDN.In this issue of Hypertension, Rosa et al present 12-month results of the Prague-15 study, which compared RDN to intensified pharmacological treatment. Per-protocol analysis showed that spironolactone addition might be more effective in blood pressure reduction than RDN with 1 year of treatment in truly resistant hypertension. Spironolactone should be considered as a part of the combination drug strategy in all resistant hypertensive patients. On the other hand, this study revealed a relatively high incidence of spironolactone side effects, especially related to antiandrogen actions.These results do not support RDN using the current techniques as a general approach to treat resistant hypertension. More effective multielectrode systems and new generation catheters remain to be established, as do potential benefits in specific patient groups. Currently, RDN should be used only in specialized hypertension centers as a part of properly designed studies.Download figureDownload PowerPointCardiovascular Effects of Living Kidney Donation (p 368)Download figureDownload PowerPointThis 1-year prospective study of kidney donors and carefully selected fit-for- donation control subjects demonstrated that the expected decline in glomerular filtration rate after donation is associated with a range of adverse cardiovascular effects including increased left ventricular mass, reduced long axis function, reduced aortic distensibility, a rise in high-sensitivity C-reactive protein, and an increased prevalence of detectable high sensitivity troponin and microalbuminuria. These findings provide a pathophysiological basis for the recent observation that kidney donors may be at increased late risk of cardiovascular events when compared with appropriate highly selected healthy controls (although their absolute risk remains lower than the general population). They also provide some evidence that a reduced glomerular filtration rate may be an independent risk factor for cardiovascular disease in the community, and that this effect may be mediated by effects on large arteries, the left ventricle, and systemic inflammation. Early-stage chronic kidney disease affects >10% of US and UK populations, so that although these effects may confer a small increase in risk to an individual, the effects on public health could be large. It has been known for some time that patients with early-stage chronic kidney disease are at greater risk of cardiovascular disease than of progression to serious renal disease. This study provides mechanistic insights into this heightened risk and suggests that efforts to reduce cardiovascular events should be centered on reducing left ventricular disease and large artery stiffness rather and not just on preventing and treating atheroma. Previous Back to top Next FiguresReferencesRelatedDetails February 2016Vol 67, Issue 2 Advertisement Article InformationMetrics © 2016 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.115.06955 Originally publishedFebruary 1, 2016 PDF download Advertisement

Early Weight Gain, Linear Growth, and Mid-Childhood Blood Pressure: A Prospective Study in Project Viva.

In recent years, the prevalence of hypertension and prehypertension increased markedly among children and adolescents, highlighting the importance of identifying determinants of elevated blood pressure early in life. Low birth weight and rapid early childhood weight gain are associated with higher future blood pressure. However, few studies have examined the timing of postnatal weight gain in relation to later blood pressure, and little is known regarding the contribution of linear growth. We studied 957 participants in Project Viva, an ongoing US prebirth cohort. We examined the relations of gains in body mass index z-score and length/height z-score during 4 early life age intervals (birth to 6 months, 6 months to 1 year, 1 to 2 years, and 2 to 3 years) with blood pressure during mid-childhood (6-10 years) and evaluated whether these relations differed by birth size. After accounting for confounders, each additional z-score gain in body mass index during birth to 6 months and 2 to 3 years was associated with 0.81 (0.15, 1.46) and 1.61 (0.33, 2.89) mm Hg higher systolic blood pressure, respectively. Length/height gain was unrelated to mid-childhood blood pressure, and there was no evidence of effect modification by birth size for body mass index or length/height z-score gain. Our findings suggest that more rapid gain in body mass index during the first 6 postnatal months and in the preschool years may lead to higher systolic blood pressure in mid-childhood, regardless of size at birth. Strategies to reduce accrual of excess adiposity during early life may reduce mid-childhood blood pressure, which may also impact adult blood pressure and cardiovascular health.

The association of renal artery calcification with hypertension in community-living individuals: the multiethnic study of atherosclerosis

Hypertension (HTN) is a modifiable risk factor for cardiovascular disease (CVD). Renal artery calcium (RAC) may signal the presence of flow-limiting atherosclerotic disease that may contribute to changes in the kidney's regulation of blood pressure. We hypothesized that RAC is independently associated with HTN. We examined a multiethnic cohort of 1285 participants who underwent abdominal computed tomography scans in five US communities. After adjustment for age, gender, race/ethnicity, CVD risk factors, abdominal aortic calcium score, and kidney function, the presence of RAC was associated with a 50% higher odds of HTN (odds ratio: 1.54; 95% confidence interval 1.11–2.13). Similarly, the presence of RAC was associated with a 8.5 mm Hg higher systolic blood pressure, a 2.1 mm Hg higher diastolic blood pressure, and a 7.4-mm Hg higher pulse pressure. In conclusion, independent of CVD risk factors, abdominal aortic calcium, and kidney function, the presence of RAC is associated with HTN prevalence.

Endotoxin and β-1,3-d-Glucan in Concentrated Ambient Particles Induce Rapid Increase in Blood Pressure in Controlled Human Exposures.

Short-term exposure to particulate matter (PM) is associated with increased blood pressure (BP) in epidemiological studies. Understanding the impact of specific PM components on BP is essential in developing effective risk-reduction strategies. We investigated the association between endotoxin and β-1,3-d-Glucan-two major biological PM components-and BP. We also examined whether vascular endothelial growth factor, a vasodilatory inflammatory marker, modified these associations. We conducted a single-blind, randomized, crossover trial of controlled human exposure to concentrated ambient particles with 50 healthy adults. Particle-associated-endotoxin and β-1,3-d-Glucan were sampled using polycarbonate-membrane-filters. Supine resting systolic BP and diastolic BP were measured pre-, 0.5-hour post-, and 20-hour postexposure. Urine vascular endothelial growth factor concentration was determined using enzyme-linked immunosorbant assay and creatinine-corrected. Exposures to endotoxin and β-1,3-d-Glucan for 130 minutes were associated with increases in BPs: at 0.5-hour postexposure, every doubling in endotoxin concentration was associated with 1.73 mm Hg higher systolic BP (95% confidence interval, 0.28, 3.18; P=0.02) and 2.07 mm Hg higher diastolic BP (95% confidence interval, 0.74, 3.39; P=0.003); every doubling in β-1,3-d-Glucan concentration was associated with 0.80 mm Hg higher systolic BP (95% confidence interval, -0.07, 1.67; P=0.07) and 0.88 mm Hg higher diastolic BP (95% confidence interval, 0.09, 1.66; P=0.03). Vascular endothelial growth factor rose after concentrated ambient particle endotoxin exposure and attenuated the association between endotoxin and 0.5-hour postexposure diastolic BP (Pinteraction=0.02). In healthy adults, short-term endotoxin and β-1,3-d-Glucan exposures were associated with increased BP. Our findings suggest that the biological PM components contribute to PM-related cardiovascular outcomes, and postexposure vascular endothelial growth factor elevation might be an adaptive response that attenuates these effects.

Mechanisms of Blood Pressure Measurement Inaccuracy: A Comparative Analysis of the Role of Occupation and Attire

Objectives: White coat hypertension (WCH) is defined as high blood pressure (BP) when measured by health care providers in medical environments, but normal BP in other settings. In this study, we examine the effects of occupation and attire on the accuracy of BP readings and WCH. Methods: 50 individuals were recruited and had their BP assessed twice by a cardiologist, a cardiac nurse, and a cardiovascular technician, once wearing a white lab coat, and once without, in random order. All individuals underwent a 24 hour ambulatory BP monitoring (ABPM). The mean of the daytime measurements of the ABPM served as the control. Results: Compared to the ABPM, the cardiologist recorded a 23.7 mm Hg higher systolic BP reading wearing a white coat and 13.3 mmHg without a white coat (p<0.0001). The cardiac nurse recorded a 14.2 mmHg higher reading with a white coat and 5.7 mmHg without a white coat (p<0.0001). There was no statistically significant difference between the measurements of the cardiovascular technician and the ABPM with a white coat, 2.8 mmHg, or without a white coat, -1.8 mmHg. Conclusions: This study demonstrates that the incidence of WCH and BP measurement inaccuracy occurs more frequently when assessed by a cardiologist or nurse than when assessed by a cardiovascular technician. Wearing a white coat aggravates blood pressure measurement inaccuracy. It may be advisable for healthcare providers to avoid wearing white lab coats or attire that identifies their occupation when measuring blood pressure.

Creatine kinase as predictor of blood pressure and hypertension. Is it all about body mass index? A follow-up study of 250 patients.

The correlation between creatine kinase (CK) and blood pressure (BP) was examined prospectively in 120 patients with persistent high CK and 130 individuals with normal CK. Hypertension was defined as systolic BP (SBP) ≥ 140 mm Hg or diastolic BP (DBP) ≥ 90 mm Hg or current use of antihypertensive medication. Baseline CK was weakly correlated with SBP (r = 0.11, P = .07) and DBP (r = 0.16, P = .01) at follow-up. Persons with persistent high CK had higher SBP (140.8 mm Hg vs 138.2 mm Hg) and DBP (83.2 mm Hg vs 81.0 mm Hg, P = .06) values and were more likely to have hypertension (66.7% vs 55.5%, P = .05) than individuals with normal CK. In age- and sex-adjusted analysis, a 1-unit change in logCK was associated with a 4.9-mm Hg higher SBP, a 3.3-mm Hg higher DBP, and a 2.2-higher odds for having hypertension at follow-up (P = .1, .07, and .06, respectively). When including body mass index (BMI) to the model, BMI was a strong and independent predictor for SBP, DBP, and hypertension at follow-up and the CK effect on blood pressure was substantially attenuated. This study showed that the CK effect on blood pressure is clearly modified by BMI.

Hypertension prevalence, awareness, treatment and control in Germany 1998 and 2008-11.

Germany was reported to have higher blood pressure (BP) and lower awareness, treatment and control of BP than other western countries based on 1998 data. BP distribution and hypertension management were examined for 1998 and 2008-11 in 7108 adult participants of the German National Health Interview and Examination Survey 1998 (GNHIES98) and in 7095 adult participants the German Health Interview and Examination Survey for Adults 2008-11 (DEGS1) aged 18-79 years. Age- and sex-standardized mean systolic BP (SBP) dropped from 129.0 to 124.1 mm Hg (women 127.3-120.8, men 130.7-127.4), mean diastolic BP (DBP) from 78.3 to 73.2 mm Hg (women 78.0-71.2, men 78.5-75.3). Mean SBP and DBP decreased most in treated hypertensives but were also lower in participants without hypertension. The overall prevalence of hypertension, including controlled hypertension, remained almost unchanged (30% vs 32%). Uncontrolled hypertension (BP⩾140/90 mm Hg) decreased from 23% to 15% (women 22-13%, men 24-18%). Among hypertensives, awareness increased from 69% to 82% (women 74-87%, men 65-78%), treatment increased from 55% to 72% (women 62-79%, men 48-65%) and control increased from 23% to 51% (women 25-58%, men 20-45%). However, men aged 18-29 years had an opposite trend with 1.5 mm Hg higher SBP and increased prevalence of hypertension, which was mostly uncontrolled. These findings suggest that BP has decreased substantially in Germany, while leaving a persistent gender gap in management and room for further improvement of prevention and treatment, particularly in men.

Relation of raw and cooked vegetable consumption to blood pressure: the INTERMAP study

Elevated blood pressure (BP) is the leading cause of premature death and disability worldwide.1 Individuals are usually characterized as ‘normotensive’ or ‘hypertensive’ based on the cut-off level of 140/90 mm Hg; however, there is no such thing as a threshold for the effect of BP on disease risk. Already from systolic BP levels of 115 mm Hg upward, there is a gradual increase in the risk for cardiovascular diseases (CVD) and mortality.2 Overall, in middle-aged populations, a 2-mm Hg higher systolic BP is associated with a 6–8% higher risk of stroke and 4–5% higher risk of coronary heart disease.2 About half of CVD occur in those with ‘normal’ BP who do not come to the attention of a clinician. Maintenance of a healthy population BP is therefore of utmost importance in the prevention of CVD. This can only be achieved when people adhere to a health-promoting lifestyle that includes body weight control, regular physical activity, low salt intake and a ‘DASH-type’ of diet.3

Genetically Altered Mutant Mouse Models of Guanylyl Cyclase/Natriuretic Peptide Receptor-A Exhibit the Cardiac Expression of Proinflammatory Mediators in a Gene-Dose-Dependent Manner

The objective of this study was to examine whether genetically determined differences in the guanylyl cyclase/natriuretic peptide receptor-A gene (Npr1) affect cardiac expression of proinflammatory cytokines, hypertrophic markers, nuclear factor-κB (NF-κB), and activating protein-1 (AP-1) in am Npr1 gene-dose-dependent manner. In the present studies, adult male Npr1 gene-disrupted (Npr1(-/-)), wild-type (Npr1(+/+)), and gene-duplicated (Npr1(++/++)) mice were used. The Npr1(-/-) mice showed 41 mm Hg higher systolic blood pressure and 60% greater heart weight to body weight (HW/BW) ratio; however, Npr1(++/++) mice exhibited 15 mm Hg lower systolic blood pressure and 12% reduced HW/BW ratio compared with Npr1(+/+) mice. Significant upregulation of gene expression of proinflammatory cytokines and hypertrophic markers along with enhanced NF-κB/AP-1 binding activities were observed in the Npr1(-/-) mouse hearts. Conversely, hypertrophic markers and proinflammatory cytokines gene expression as well as NF-κB/AP-1 binding activities were markedly decreased in Npr1(++/++) mouse hearts compared with wild-type mice. The ventricular guanylyl cyclase activity and cGMP levels were reduced by 96% and 87%, respectively, in Npr1(-/-) mice; however, these parameters were amplified by 2.8-fold and 3.8-fold, respectively, in Npr1(++/++) mice. Echocardiographic analysis revealed significantly increased fractional shortening in Npr1(++/++) mice (P < .05) but greatly decreased in Npr1(-/-) mice (P < .01) hearts compared with Npr1(+/+) mice. The present findings suggest that Npr1 represses the expression of cardiac proinflammatory mediators, hypertrophic markers, and NF-κB/AP-1-mediated mechanisms, which seem to be associated in an Npr1 gene-dose-dependent manner.

Adiposity and glucose intolerance exacerbate components of metabolic syndrome in children consuming sugar‐sweetened beverages: QUALITY cohort study

Sugar-sweetened beverage (SSB) consumption is linked to weight gain and metabolic syndrome (MetS) components in children, but whether these associations are modified by excess weight and glucose tolerance status in children is not known. The objective of this study was to examine the cross-sectional associations between SSB intake and MetS components among children above and below the 85th body mass index (BMI) percentile and those with and without impaired glucose tolerance (IGT). Data were from the QUébec Adiposity and Lifestyle InvesTigation in Youth study (2005-2008). Caucasian children aged 8-10 years (n = 632) were recruited from 1040 primary schools in Québec, Canada. SSB consumption was assessed by three 24-h dietary recalls, body fat mass by dual-energy absorptiometry, physical activity by 7-d accelerometer. Multivariate linear regressions were used, with age, sex, fat mass index and physical activity as covariates, including waist circumference (WC), systolic blood pressure (SBP), concentrations of triglyceride and high-density lipoprotein cholesterol and homeostasis model assessment of insulin resistance (HOMA-IR) as outcome variables. Among overweight children, a 100-mL higher SSB consumption was associated with a 0.1-unit higher HOMA-IR (P = 0.009) and a 1.1-mm Hg higher SBP (P = 0.001). In children with IGT, a 100-mL higher SSB consumption was associated with a 1.4-mm Hg higher SBP and a 4.0-cm higher WC (P < 0.001). These associations were not observed among children <85th BMI percentile. Our results suggest that the association between higher SSB consumption and MetS components is more evident in overweight/obese and glucose-intolerant children.

Clinical Implications

HomeHypertensionVol. 60, No. 5Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Nov 2012https://doi.org/10.1161/HYP.0b013e31827679abHypertension. 2012;60:1087Blood Pressure Characteristics and Early Onset Preeclampsia (page 1338)Download figureDownload PowerPointSome women develop preeclampsia very early in their pregnancy. Interestingly, such women are also more likely to have a family history of preeclampsia, develop preeclampsia again in subsequent pregnancies, and have a higher risk of later cardiovascular disease. These observations raise the possibility that women develop early onset preeclampsia because they have distinct, heritable, physiological traits that predispose them to both preeclampsia and later cardiovascular disease. In this issue of Hypertension, Lazdam et al report distinct differences in blood pressure characteristics during pregnancy, and <13 years later, in women who develop early onset preeclampsia. They demonstrate for the first time that compared with those with late-onset preeclampsia or normotensive pregnancies, such women have persistently higher blood pressure 6 weeks after delivery, a substantially greater increase in blood pressure over the next decade relative to levels during pregnancy, and significantly higher nocturnal blood pressures in later life. Lazdam et al then studied blood pressure in the offspring and found that those born to the pregnancies complicated by early onset disease had 6 mm Hg higher systolic blood pressure compared with those born to either late-onset disease or normotensive pregnancy. Characterization of the biology that underlies these distinct variations in blood pressure behavior may identify pathways for novel interventions. Furthermore, a diagnosis of early onset disease seems to identify individuals who may warrant targeted blood pressure surveillance.Determinants of Adolescent Left Ventricular Mass (page 1266)Cardiac left ventricular hypertrophy is a strong independent predictor of cardiovascular disease morbidity and mortality in adulthood. Left ventricular growth and geometric remodeling in adolescence may have long-term consequences on cardiovascular health in later life. However, factors influencing left ventricular mass in early life are poorly characterized. The determinants of left ventricular mass and patterns of geometric remodeling in healthy adolescents with specific emphasis on birth size and growth in early childhood were studied. Left ventricular measurements were obtained with echocardiography in 418 adolescents at 15 years of age in a prospective atherosclerosis prevention study, Special Turku Coronary Risk Factor Intervention Project (STRIP). Birth weight was directly associated with left ventricular mass, regardless of sex and current weight, pulse pressure, and physical activity level. Growth in early childhood was not associated with left ventricular mass in adolescence. Adolescents who were overweight had 17 g greater left ventricular mass than those with normal body mass index. The results indicate that birth weight has a long-lasting impact on left ventricular mass and normal body weight is beneficial for cardiac structure in adolescents, whereas weight gain during the first 2 years of life does not associate with adolescent left ventricular mass. These data extend the knowledge of the determinants of left ventricular mass from early life to adolescence, relevant for the prevention of cardiovascular disease.Is Blood Pressure Variability a Risk Factor? (page 1138)Download figureDownload PowerPointAttempts to anchor blood pressure variability as an established cardiovascular risk factor span ≈30 years. Recent findings challenge the concept of usual blood pressure and led to the proposition to consider blood pressure variability in the diagnosis, treatment, and monitoring of patients with hypertension. Because these findings originated from post hoc analyses within the context of clinical trials in selected high-risk patients or in patients with a history of stroke, confirmation from an unbiased population sample was necessary. In this issue of Hypertension, results from the prospective Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO) indicate that systolic blood pressure variability does not have any independent prognostic significance over and beyond mean systolic pressure. These findings from 2944 randomly recruited participants, representative of a general population, and followed up for a median of 12 years, suggest that what matters most in the management of hypertension is to reduce the blood pressure level, as recommended in current guidelines. FLEMENGHO results do not support blood pressure variability as an independent risk factor. Previous Back to top Next FiguresReferencesRelatedDetails November 2012Vol 60, Issue 5 Advertisement Article InformationMetrics © 2012 American Heart Association, Inc.https://doi.org/10.1161/HYP.0b013e31827679ab Originally publishedNovember 1, 2012 PDF download Advertisement

Association of Genetic Variation in the Mitochondrial Genome With Blood Pressure and Metabolic Traits

Elevated blood pressure (BP) is a major risk factor for cardiovascular disease. Several studies have noted a consistent maternal effect on BP; consequently, mitochondrial DNA variation has become an additional target of investigation of the missing BP heritability. Analyses of common mitochondrial DNA polymorphisms, however, have not found evidence of association with hypertension. To explore associations of uncommon (frequency>5%) mitochon drial DNA variants with BP, we identified uncommon/rare variants through sequencing the entire mitochondrial genome in 32 unrelated individuals with extreme-high BP in the Framingham Heart Study and genotyped 40 mitochondrial single nucleotide polymorphisms in 7219 Framingham Heart Study participants. The nonsynonymous mitochondrial single nucleotide polymorphism 5913G>A (Asp4Asn) in the cytochrome c oxidase subunit 1 of respiratory complex IV demonstrated significant associations with BP and fasting blood glucose (FBG) levels. Individuals with the rare 5913A allele had, on average, 7-mm Hg higher systolic BP at baseline (Pempirical=0.05) and 17-mg/dL higher mean FBG over 25 years of follow-up (Pempirical=0.009). Significant associations with FBG levels were also detected for nonsynonymous mitochondrial single nucleotide polymorphism 3316G>A (Ala4Thr) in the NADH dehydrogenase subunit 1 of complex I. On average, individuals with rare allele 3316A had 17- and 25-mg/dL higher FBG at baseline (Pempirical=0.01) and over 25 years of follow-up (Pempirical=0.007). Our findings provide the first evidence of putative association of variants in the mitochondrial genome with systolic BP and FBG in the general population. Replication in independent samples, however, is needed to confirm these putative associations.