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Home Blood Pressure in Health and Disease
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.ORCID iD: 0000-0001-6038-5131
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hypertension is the most common preventable cause of premature all-cause mortality, primarily from cardiovascular disease (CVD). Individuals with dysglycemia, including prediabetes and diabetes, are at increased risk. Licorice intake raises blood pressure (BP) through the effects of glycyrrhizic acid (GA), but the true limit of safe intake is uncertain. Home BP has several benefits over BP measured at a clinic, including a higher predictive value for CVD. By combining office and home BP, it is possible to diagnose masked hypertension (MH), in which home but not office BP is elevated, and white coat hypertension (WCH), in which office but not home BP is elevated. The aim of this thesis was to advance our knowledge on home BP in relation to dysglycemia, markers of CVD, and licorice intake.  

The first 3 papers used data from the Linköping cohort of the prospective Swedish CArdioPulmonary bioImage Study (SCAPIS). Study IV was a randomized controlled cross-over study. Data was obtained from questionnaires, blood samples and office and home BP measurements. In studies I-III, pulse wave velocity (PWV), coronary artery calcium score (CACS), and carotid artery plaques as markers of CVD were also included.  

In Study I, we examined 5025 men and women aged 50-64 years old for the relation between dysglycemia and home BP. Both the systolic office and home BP measurements were positively as-sociated with dysglycemia. Participants with dysglycemia vs normoglycemia more often had MH. The findings were in line with previous research and strengthened the association between dysglycemia and MH.  

In Study II, we examined the associations between MH and markers of CVD in 4122 individuals without BP-lowering treatment. Of participants, 4.2% had MH, and these were more often men and had higher BMI than those with normotension. Participants with MH also had higher odds for CACS ≥100, an as-sociation which has previously been suggested as a trend.

In Study III, we examined the relation between soluble P-se-lectin (sP-selectin) as a measure of thrombotic activity, plasma high-sensitivity C-reactive protein (hsCRP) as a measure of inflammation, and home BP in 4548 participants. Both markers were higher in each hypertension phenotype compared with sustained normotension. The quartile of participants with the highest sP-se-lectin values had higher odds for CACS ≥100 and carotid artery plaques. The association between sP-selectin and sustained hyper-tension was novel and not affected by adjustments for hsCRP.  

In Study IV, 28 healthy participants aged 18-30 years old were evaluated for the effects of a daily intake of licorice containing 100 mg of GA compared with a control product for 2 weeks. During the licorice intake period, the systolic home BP increased with 3.1 mmHg, and the suppression of serum aldosterone and plasma renin levels indicated that this was due to the licorice intake.  

In conclusion, this thesis further strengthens the idea that both home and office BP measurements have values beyond that of the other, and that home BP may be most valuable in individuals with dysglycemia and obesity, and in men. Finally, licorice may be more potent than previously known, suggesting the need for increased awareness. 

Abstract [sv]

Förhöjt blodtryck (hypertoni) är den huvudsakliga orsaken till förtida död, främst genom hjärtkärlsjukdom. Flera mekanismer och riskfaktorer som kan förklara hypertoni har identifierats. Individer med förhöjt blodsocker, inklusive diabetes och dess förstadier, lö-per ökad risk för hjärtkärlsjukdom, och förhöjt blodsocker samexisterar ofta med hypertoni. Lakritsintag höjer blodtrycket genom dess beståndsdel glycyrrhizinsyra (GA), och även om både Europeiska unionen och Världshälsoorganisationen har föreslagit att ett intag av upp till 100 mg per dag sannolikt är säkert att förtära för de flesta individer, är den gränsnivån osäker.  

Jämfört med blodtryck som mäts på mottagningen av medicinskt utbildad personal har hemblodtryck flera fördelar, inklusive starkare koppling till framtida hjärtkärlsjukdom. Genom att kombinera mottagnings- och hemblodtryck går det att diagnosticera maskerad hypertoni (MH), då hemblodtrycket är förhöjt trots normalt mottagningsblodtryck, och vitrockhypertoni (WCH), då mottagningsblodtrycket men inte hemblodtrycket är förhöjd. Syftet med denna avhandling var att vidare utforska hemblodtryck i relation till förhöjt blodsocker, markörer för hjärtkärlsjukdom, och lakritsintag.  

Avhandlingens fyra arbeten baseras på två studier. I de första tre arbetena analyserades data från Linköpings-kohorten i the Swedish CArdioPulmonary bioImage Study (SCAPIS), en prospektiv studie av män och kvinnor i åldrarna 50-64 år. I det sista arbetet analyserades data från en lottad överkorsningsstudie. Data i studierna bestod av enkätsvar, blodprover, samt mottagnings- och hemblodtrycksmätningar. I studie I-III ingick även pulsvågshastighet, kalkhalt i kranskärlen vid skiktröntgen (CACS) och plack-förekomst i halspulsådrorna vid ultraljudsundersökning som markörer på hjärtkärlsjukdom.  

I det första delarbetet undersökte vi data för 5025 individer avseende blodtryck och förhöjt blodsocker. Både mottagnings- och hemblodtryck var associerat med förhöjt blodsocker. Deltagare med förhöjt blodsocker hade oftare MH jämfört med de med normalt blodsocker, och skillnaden mellan mottagnings- och hemblodtrycket var omvänt associerat med långtidsblodsocker. Fynden var i linje med tidigare forskning, och stärkte kända kopplingar mellan MH och förhöjt blodsocker. Förklaringarna till detta samband är okända, men möjliga sådana inkluderar selektiva effekter av blodtryckssänkande läkemedel hos individer med förhöjt blodsocker, samsjukligheter såsom fetma, och aktivering av det sympatiska nervsystemet.  

I det andra delarbetet analyserade vi förekomst av och associationer för MH hos 4122 individer utan pågående blodtryckssänkande läkemedelsbehandling. Av dessa hade 4.2% MH, och dessa var oftare män och hade högre BMI än de med normalt blodtryck. Deltagare med MH hade också högre pulsvågshastighet och oftare förhöjt CACS. Associationen mellan MH och markörer för hjärt-kärlsjukdom var tidigare känd och styrktes av våra resultat.  

I det tredje delarbetet undersökte vi 4548 deltagare avseende två blodprovsmarkörer: en för blodplättsaktivitet, lösligt P-selektin i blodet, och en för inflammation, högkänsligt C-reaktivt protein (hsCRP). Både P-selektin och hsCRP var högre vid hypertoni, oavsett typ, jämfört med vid normalt blodtryck. Den kvartil av deltagarna som hade högst P-selektin hade oftare WCH och hypertoni både hemma och på mottagningen, jämfört med normalt blodtryck, och oftare förhöjt CACS och plack i halspulsådrorna. Associationen mellan P-selektin och högt blodtryck både hemma och på mottagningen var inte tidigare känd, och påverkades inte av justering för hsCRP, vilket antydde att den inte enbart förklarades av inflammation.  

I det fjärde och sista delarbetet inkluderas 28 friska individer i åldrarna 18 till 30 år. I en överkorsningsstudie bad vi deltagarna att dagligen under 2 veckor inta antingen lakrits med ett innehåll av 100 mg GA eller en kontrollprodukt utan lakrits. Deltagarna undersöktes med avseende på hemblodtryck, liksom hormonnivåer i blodet. Under lakrits- jämfört med kontrollperioden steg det systoliska hemblodtrycket med 3,1 mmHg, och hormonnivåerna påverkades på ett sätt som talade för att GA påverkade blodtrycket.  

Sammanfattningsvis stärker studiernas resultat kunskapen om att blodtrycksmätning både på mottagningen och i hemmet är värdefullt både var för sig och tillsammans, och att hemblodtryck är särskilt värdefullt hos individer med förhöjt blodsocker eller övervikt, samt hos män. Slutligen visade sig små mängder lakrits påverka kroppen mer än tidigare känt, och ökad medvetenhet och bättre etikettering av lakritsprodukter kan vara befogad.  

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2024. , p. 167
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1918
National Category
Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:liu:diva-205883DOI: 10.3384/9789180756563ISBN: 9789180756556 (print)ISBN: 9789180756563 (electronic)OAI: oai:DiVA.org:liu-205883DiVA, id: diva2:1882840
Public defence
2024-09-06, K3, Önnesjösalen, Campus Norrköping, Norrköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2024-07-08 Created: 2024-07-08 Last updated: 2024-07-09Bibliographically approved
List of papers
1. Home Blood Pressure Compared With Office Blood Pressure in Relation to Dysglycemia
Open this publication in new window or tab >>Home Blood Pressure Compared With Office Blood Pressure in Relation to Dysglycemia
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2022 (English)In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 35, no 9, p. 810-819Article in journal (Refereed) Published
Abstract [en]

Background: Masked hypertension is more common in individuals with type 2 diabetes than in individuals with normoglycemia. We aimed to explore if there is a discrepancy between office blood pressure (office BP) and home blood pressure monitoring (HBPM) in relation to HbA1c as well as glycemic status in 5,029 middle-aged individuals.

Methods: HBPM was measured in a subsample of 5,029 participants in The Swedish CardioPulmonary BioImage Study (SCAPIS), a population-based cohort of 50–64 years old participants. Both office BP and HBPM were obtained after 5 minutes’ rest using the semiautomatic Omron M10-IT oscillometric device. White coat effect was calculated by subtracting systolic HBPM from systolic office BP. Participants were classified according to glycemic status: Normoglycemia, prediabetes, or diabetes based on fasting glucose, HbA1c value, and self-reported diabetes diagnosis.

Results: Of the included 5,025 participants, 947 (18.8%) had sustained hypertension, 907 (18.0%) reported taking antihypertensive treatment, and 370 (7.4%) had diabetes mellitus. Both systolic office BP and HBPM increased according to worsened glycemic status (P for trend 0.002 and 0.002, respectively). Masked hypertension was more prevalent in participants with dysglycemia compared with normoglycemia (P = 0.036). The systolic white coat effect was reversely associated with HbA1c (P = 0.012).

Conclusions: The systolic white coat effect was reversely associated with HbA1c, and the prevalence of masked hypertension increased with dysglycemia.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Oxford University Press, 2022
Keywords
blood pressure, cardiovascular disease, diabetes, dysglycemia, HbA1c, home blood pressure monitoring, hypertension, white coat effect
National Category
General Practice Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-187063 (URN)10.1093/ajh/hpac082 (DOI)000826969200001 ()35849046 (PubMedID)
Note

Funding: The main funding body of The Swedish CArdioPulmonary bioImage Study(SCAPIS) is the Swedish Heart and Lung Foundation [2016-0315]. The study is also funded by the Knut and Alice Wallenberg Foundation [2014-0047], the Swedish Research Council [822-2013-2000], VINNOVA (Sweden’s Innovation agency) [2012-04476], the University of Gothenburg and Sahlgrenska University Hospital, Karolinska Institutet and Stockholm county council, Linköping University and University Hospital, Lund University and Skåne University Hospital, Umeå University and University Hospital, Uppsala University and University Hospital, the Swedish state under the agreement between the Swedish government and the county councils (the ALF-agreement), and the King Gustaf V and Queen Victoria’s Foundation of Freemasons.

Available from: 2022-07-20 Created: 2022-07-20 Last updated: 2024-07-08Bibliographically approved
2. Masked hypertension in a middle-aged population and its relation to manifestations of vascular disease
Open this publication in new window or tab >>Masked hypertension in a middle-aged population and its relation to manifestations of vascular disease
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2023 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 41, no 7, p. 1084-1091Article in journal (Refereed) Published
Abstract [en]

Background: Masked hypertension is associated with cardiovascular disease (CVD). However, previous large studies have not used the same device to measure office and home blood pressure (BP) and adhered to current home BP measurement recommendations of the European Society of Hypertension. We aimed to characterize masked hypertension and explore its relation to manifestations of CVD.

Methods: A randomly selected cohort of 5057 participants aged 50–64 years from the Swedish CardioPulmonary BioImage Study (SCAPIS) was evaluated with office and home BP using the semi-automatic Omron M10-IT oscillometric device. Additional analyses included pulse wave velocity (PWV) and coronary artery calcium score (CACS).

Results: Of participants, 4122 did not have current antihypertensive treatment, and were thus included in our analyses. Of these, 2634 (63.9%) had sustained normotension, and 172 (4.2%) had masked hypertension. Participants with masked hypertension vs. sustained normotension were more often men (66.9 vs. 46.2%, P < 0.001). Those with masked hypertension had higher mean PWV [9.3 (95% confidence interval, 95% CI 9.1–9.5) vs. 8.3 (95% CI 8.2–8.4) m/s, P < 0.001] and odds ratio for CACS at least 100 [1.65 (95% CI 1.02–2.68), P = 0.040]. These associations were similar in a posthoc analysis of masked hypertension and sustained normotension, matched for age, sex and systolic office BP.

Conclusion: Masked hypertension was associated with markers of CVD. This suggests that home BP is a better predictor of risk, even when the recordings are performed with the same measurement device, in a population-based setting with randomized recruitment.

Place, publisher, year, edition, pages
Wolters Kluwer, 2023
Keywords
blood pressure, cardiovascular disease, carotid artery plaques, coronary artery calcium score, home blood pressure, masked hypertension, pulse wave velocity
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-192987 (URN)10.1097/hjh.0000000000003431 (DOI)001000477000005 ()37016927 (PubMedID)
Note

Funding: Swedish Heart and Lung Foundation [20160315]; Knut and Alice Wallenberg Foundation [20140047]; Swedish Research Council [82220132000]; VINNOVA (Swedens Innovation agency) [201204476]; University of Gothenburg; Sahlgrenska University Hospital; Karolinska Institutet; Stockholm County council; Linkoping University; Linkoping University Hospital; Lund University; Skane University Hospital; Umea~University; Umea University Hospital; Uppsala University; Uppsala University Hospital; Strategic Research Network in Circulation and Metabolism at Linkoping University (LiU-CircM); King Gustaf V and Queen Victoria Freemason Foundation

Available from: 2023-04-07 Created: 2023-04-07 Last updated: 2024-07-08
3. P-selectin and C-reactive protein in relation to home blood pressure and coronary calcification: a SCAPIS substudy
Open this publication in new window or tab >>P-selectin and C-reactive protein in relation to home blood pressure and coronary calcification: a SCAPIS substudy
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2024 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques.

Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques.

Results: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4–61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40–1.98, P < 0.001] and hsCRP [OR 2.25, (95% CI 1.89–2.60), P < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72–3.10), P < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05–1.38), P = 0.007.

Conclusion: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2024
Keywords
Blood pressure, selectin, CRP, inflammation, hypertension, cardiovascular disease, CACS, carotid artery plaques, masked hypertension
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-203174 (URN)10.1097/HJH.0000000000003718 (DOI)38690927 (PubMedID)
Available from: 2024-05-01 Created: 2024-05-01 Last updated: 2024-07-08Bibliographically approved
4. A low dose of daily licorice intake affects renin, aldosterone, and home blood pressure in a randomized crossover trial
Open this publication in new window or tab >>A low dose of daily licorice intake affects renin, aldosterone, and home blood pressure in a randomized crossover trial
2024 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 119, no 3, p. 682-691Article in journal (Refereed) Published
Abstract [en]

Background

Licorice, through the effects of glycyrrhizic acid (GA), raises blood pressure (BP). The World Health Organization has suggested that 100 mg GA/d would be unlikely to cause adverse effects, but of 13 previously published studies none have been randomized and controlled and independently quantified the GA content.

Objective

Our aim was to analyze the effects on home BP of a daily licorice intake containing 100 mg GA.

Methods

Healthy volunteers were randomly assigned to start with either licorice or a control product in a nonblinded, 2 × 2 crossover study. Home BP was measured daily, and blood samples were collected at the end of each 2-wk period.

Results

There were 28 participants and no dropouts. The median age was 24.0 y (interquartile range 22.8–27.0 y). During the licorice compared with control intake period, the systolic home BP increased [mean difference: 3.1 mm Hg (95% confidence interval [CI]: 0.8, 5.4 mm Hg) compared with −0.3 mm Hg (95% CI: −1.8, 1.3 mm Hg); P = 0.018] and renin and aldosterone were suppressed [mean change: −30.0% (95% CI: −56.7%, −3.3%) compared with 15.8% (95% CI: −12.8%, 44.4%); P = 0.003; and −45.1% (95% CI: −61.5%, −28.7%) compared with 8.2% (95% CI: −14.7%, 31.1%); P <0.001, respectively]. In the quartile of participants with the most pronounced suppression of renin and aldosterone, N-terminal prohormone of brain natriuretic peptide concentration increased during the licorice compared with control period [mean change: 204.1% (95% CI: −11.6%, 419.7%) compared with 72.4% (95% CI: −52.2%, 197.1%); P = 0.016].

Conclusions

We found licorice to be more potent than previously known, with significant increases in BP, after a daily intake of only 100 mg GA. Thus, the safe limit of intake of this substance might need to be reconsidered.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2024
Keywords
aldosterone, glycyrrhizic acid, home blood pressure, licorice, renin, aldosteron, glycyrrhizinsyra, hemblodtryck, lakrits, renin
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-200860 (URN)10.1016/j.ajcnut.2024.01.011 (DOI)001209261000001 ()38246526 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF)Konung Gustaf V:s och Drottning Victorias FrimurarestiftelseSwedish Heart Lung FoundationSwedish Society of MedicineRegion Östergötland, RÖ 988832, RÖ 2021/3845,RÖ 2022/13418
Note

Funding Agencies|Strategic Research Network in Circulation and Metabolism at Linkoping University (LiU-CircM); National Research School in General Practice; Swedish Society of Medicine; Swedish Society for Medical Research; King Gustaf V and Queen Victoria Freemason Foundation; Swedish Heart Lung Foundation; Region Ostergotland; Primary Health Care Centers Research Fund, Region Ostergotland, Sweden;  [RO 988832];  [RO 2021/3845];  [RO 2022/13418]

Available from: 2024-02-12 Created: 2024-02-12 Last updated: 2024-07-08

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