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Age and gender differences in risk factor burden, myocardial dysfunction and cardiovascular events in relation to glucose metabolism

Leosdottir, Margrét LU (2012) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2012:16.
Abstract (Swedish)
Popular Abstract in Swedish

Studier har visat att inte bara individer med diabetes utan ocksa de som har forstadier till diabetes, namligen forhojt fasteblodsocker och nedsatt glukostolerans, loper en okad risk for att drabbas av saval hjartkarlsjukdom som hjartsvikt. Daremot har man sett att den okade risken forenad med diabetes verkar minska med aldern. Studier pa aldre individer ar dock sparsamma, de studier som finns ar begransade till diabetiker, och ofta rapporteras inte resultaten atskilt for man och kvinnor. Det overgripande syftet med de fyra delarbeten som presenterats i denna avhandling var att ta reda pa om det finns skillnader mellan medelalders och aldre man respektive kvinnor avseende sambandet mellan stord... (More)
Popular Abstract in Swedish

Studier har visat att inte bara individer med diabetes utan ocksa de som har forstadier till diabetes, namligen forhojt fasteblodsocker och nedsatt glukostolerans, loper en okad risk for att drabbas av saval hjartkarlsjukdom som hjartsvikt. Daremot har man sett att den okade risken forenad med diabetes verkar minska med aldern. Studier pa aldre individer ar dock sparsamma, de studier som finns ar begransade till diabetiker, och ofta rapporteras inte resultaten atskilt for man och kvinnor. Det overgripande syftet med de fyra delarbeten som presenterats i denna avhandling var att ta reda pa om det finns skillnader mellan medelalders och aldre man respektive kvinnor avseende sambandet mellan stord glukosmetabolism (fran normalt fasteblodsocker till kand diabetes), riskfaktorer for hjartkarlsjukdom, tidig hjartdysfunktion och risken for hjartkarl-handelser sasom hjartinfarkt och stroke.



Pa 1970-talet startade ett primarpreventivt projekt vid Medicinska kliniken, UMAS (numera Skanes Universitetssjukhus) i Malmo. Projektet som kallades Malmo Forebyggande Medicin (MFM) borjade 1974. Under 17 ar blev totalt 33 000 man och kvinnor undersokta med frageformular, blodprover och kroppslig undersokning. I borjan av 2000-talet bjods alla kvarlevande som deltagit i MFM in till en aterundersokning dar aterigen deltagarna fick svara pa frageformular och fick taget blodprov, man tog puls och blodtryck, matte langd, vikt, stuss och midjematt. Totalt deltog drygt 18 000 medelalders och aldre man och kvinnor denna gang. Hos en mindre grupp (ca 1800 deltagare) genomfordes ultraljudsundersokning pa hjartat, man tog EKG och ett speciellt blodprov som kallas Nt-proBNP, vilket aterspeglar belastning i hjartat. Deltagarna har sedan dess foljts upp i nationella register avseende hjartkarl-handelser.



Ett liknande projekt, Reykjavik studien, genomfordes i Island pa sjuttio- och attiotalet. Aven dar kallades deltagarna tillbaka i borjan pa 2000-talet. Totalt deltog ca 5700 i aterundersokningen i Reykjavik, varav 900 undersoktes med ultraljud pa hjartat. Dessa tva stora befolkningsstudier gav underlag till studierna i avhandlingen.



Bland hjartfriska medelalders (57-69 ar) man och kvinnor blev hjartdysfunktion matt med ultraljud mer uttalad ju hogre socker deltagarna hade. Samma fynd sag man inte bland aldre (70-80 ar) man och kvinnor dar de som hade sockerrubbningar inte hade tecken till hjartdysfunktion i nagon storre utstreckning an de som hade normal sockerbalans.



Hos medelalders man steg Nt-proBNP jo hogre socker mannen hade. Ett positivt samband mellan socker och Nt-proBNP sags ocksa hos de aldre mannen, men dar var sambandet svagare och icke statistiskt signifikant. Hos kvinnorna sags ett omvant samband; jo hogre socker de hade, desto lagre Nt-proBNP varde. Sambandet var dock varken signifikant hos de medelalders eller de aldre kvinnorna. Fynden forstarker resultaten fran ultraljudsundersokningarna, d.v.s. att hjartdysfunktion verkar inte forekomma i storre utstreckning hos aldre individer med sockerrubbningar an hos de som har normalt socker.



Nar man analyserade riskfaktorer for hjartkarlsjukdom (sasom hogt blodtryck, rokning och hogt kolesterol) och sjalvskattad halsa hittade man daremot en klart okad riskfaktorbelastning och samre sjalvskattad halsa med stigande blodsocker bade hos medelalders och aldre deltagare. Over lag sa var riskfaktorbordan storre och den sjalvskattade halsan samre hos kvinnor, och dessa forsamrades mer med stigande socker bland de aldre kvinnorna an de aldre mannen.



Nar man till slut analyserade hjartkarlhandelser sag man att ju hogre socker medelalders man och kvinnor hade vid studiestarten, desto storre risk fanns for att de hade drabbats av hjartinfarkt eller stroke under uppfoljningstiden. Samma okning sags inte bland de aldre, dar sockret verkade inte ha nagon storre effekt pa risken. Hos bade medelalders och aldre man och kvinnor med diagnosticerad diabetes, daremot, var risken for att utveckla hjartinfarkt eller stroke okad jamfort med de som hade normalt fasteblodsocker.



Slutsatserna att dra av dessa studier ar att forhojt blodsocker inte verkar ha lika mycket effekt pa hjartfunktionen och risken for att drabbas av hjartinfarkt och stroke hos aldre som hos medelalders man och kvinnor. Att ha forhojt blodsocker ar dock forenad med en ansamling av ovriga riskfaktorer for hjartkarlsjukdom och forsamrad sjalvskattad halsa hos aldre likaval som hos de som ar i medelaldern, mer sa hos kvinnor an hos man relativt sett. (Less)
Abstract
The risk of cardiovascular disease (CVD) and heart failure (HF) among individuals with diabetes is at least two times greater than in non-diabetic subjects. However, the excess risk of CVD in diabetic subjects seems to decrease with age. As the majority of patients with diabetes, CVD and HF are elderly it is important to establish the extent to which the associations between these conditions differ from those in younger populations. The overall aim of the work presented in this thesis was to study gender-related associations between glucose metabolism and myocardial dysfunction, risk factor burden and CVD events in middle-aged and elderly subjects. The hypothesis tested was that similar associations would be observed in elderly as in... (More)
The risk of cardiovascular disease (CVD) and heart failure (HF) among individuals with diabetes is at least two times greater than in non-diabetic subjects. However, the excess risk of CVD in diabetic subjects seems to decrease with age. As the majority of patients with diabetes, CVD and HF are elderly it is important to establish the extent to which the associations between these conditions differ from those in younger populations. The overall aim of the work presented in this thesis was to study gender-related associations between glucose metabolism and myocardial dysfunction, risk factor burden and CVD events in middle-aged and elderly subjects. The hypothesis tested was that similar associations would be observed in elderly as in younger populations, although the associations would be weaker with advancing age. Data from two population-based cohort studies were used: MPP-RES (Sweden: n=18,238, mean age 69+/-6 years, range 57-86 years) and AGES-RS (Iceland: n=5,764, mean age 76+/-6 years, range 67-95).



In Paper I the associations between echocardiographic indices of left ventricular diastolic dysfunction (LVDD), LV mass index (LVMI) and glucometabolic status were studied in echocardiography subcohorts from the two cohort studies (MPP-RES n=1,792; AGES-RS n=841). The MPP-RES cohort was divided into two age groups: middle-aged (57-69 years) and elderly subjects (70-80 years). All subjects were grouped according to fasting glucose level (FG, mmol/l): =<5.0; 5.1-5.5; 5.6-6.0 and 6.1-6.9 (pre-diabetic range) and >=7.0 (new-onset diabetes) and established diabetes, and trends between the groups were assessed. Few and inconsistent associations were observed in the AGES-RS cohort and in the elderly group in the MPP-RES cohort between increasing glucometabolic impairment and measures of LVDD. These observations are in contrast to previous findings in younger subjects as well as the present findings in the middle-aged group in the MPP-RES cohort, where a significant association was found between increasing LVDD and increasing glucometabolic impairment. It was concluded that changes in LV diastolic function may be more related to age than glucose metabolism in elderly subjects.



In Paper II possible associations between N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and FG as a continuous variable and in FG groups (as in Paper I) were assessed in the MPP-RES echocardiography subcohort. A positive correlation was found between Nt-proBNP and FG among middle-aged men. A positive correlation was also observed among elderly men, albeit non-significant. A non-significant negative correlation was observed among women in both age groups. The results indicate that caution should probably be exercised when interpreting Nt-proBNP values in subjects with impaired glucose metabolism.



In Paper III the strength of the correlation between glucometabolic impairment, CVD risk factor burden and self-rated health (SRH), in middle-aged and elderly groups in the whole MPP-RES cohort (n=18,238) was compared. Correlations between increasing glucometabolic impairment and CVD risk factor burden and the proportion of subjects reporting poor SRH increased for both men and women in both age groups (p-trend <0.0001 for all). The slope of the trend curve with increasing CVD risk factor burden was significantly steeper for elderly women than for elderly men (p-interaction=0.002). The slope of the trend curve for poor SRH was significantly steeper for middle-aged than for elderly men (p-interaction=0.005), while no difference was observed between the age groups in the women. These results indicate lifelong CVD risk factor clustering and poorer SRH with increased glucometabolic impairment, being somewhat more pronounced in elderly women than in elderly men.



Finally, in Paper IV we examined whether the previously observed age-related reduction in excess CVD risk for diabetic compared to non-diabetic subjects also applies to pre-diabetic conditions. The MPP-RES cohort was followed for 4.1+/-1.3 years during which 1,296 CVD events occurred. Subjects were grouped by FG, gender and age, as previously. The hazard ratios for CVD events increased with increasing FG among middle-aged men and women. No comparable increase was observed among elderly subjects, where men with FG =<5.0-6.9 and women with FG =<5.0-6.0 had HRs close to 1.0. The B-coefficients for interaction between age groups and intergroup trends were -0.17 (unadjusted p=0.01) and -0.15 (fully adjusted p=0.03) for men, and -0.13 (p=0.27) for women (irrespective of adjustment). It was concluded that FG values within the upper pre-diabetic range conveyed less excess risk of CVD events among elderly than middle-aged men and women. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor emeritus Ryden, Lars, Karolinska Institutet, Stockholm
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Age, cardiovascular disease, diabetes, echocardiography, gender, glucose, left ventricular function, Nt-proBNP, self-rated health
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2012:16
pages
152 pages
publisher
Lund University
defense location
Medicinens Aula, Ingang 35, Skånes Universitetssjukhus, Malmo
defense date
2012-03-02 09:15
ISSN
1652-8220
ISBN
978-91-86871-78-9
language
English
LU publication?
yes
id
938a9dd5-6c02-4857-b488-89b5a5155e5f (old id 2340709)
date added to LUP
2012-02-14 11:01:37
date last changed
2016-09-19 08:44:51
@phdthesis{938a9dd5-6c02-4857-b488-89b5a5155e5f,
  abstract     = {The risk of cardiovascular disease (CVD) and heart failure (HF) among individuals with diabetes is at least two times greater than in non-diabetic subjects. However, the excess risk of CVD in diabetic subjects seems to decrease with age. As the majority of patients with diabetes, CVD and HF are elderly it is important to establish the extent to which the associations between these conditions differ from those in younger populations. The overall aim of the work presented in this thesis was to study gender-related associations between glucose metabolism and myocardial dysfunction, risk factor burden and CVD events in middle-aged and elderly subjects. The hypothesis tested was that similar associations would be observed in elderly as in younger populations, although the associations would be weaker with advancing age. Data from two population-based cohort studies were used: MPP-RES (Sweden: n=18,238, mean age 69+/-6 years, range 57-86 years) and AGES-RS (Iceland: n=5,764, mean age 76+/-6 years, range 67-95).<br/><br>
<br/><br>
In Paper I the associations between echocardiographic indices of left ventricular diastolic dysfunction (LVDD), LV mass index (LVMI) and glucometabolic status were studied in echocardiography subcohorts from the two cohort studies (MPP-RES n=1,792; AGES-RS n=841). The MPP-RES cohort was divided into two age groups: middle-aged (57-69 years) and elderly subjects (70-80 years). All subjects were grouped according to fasting glucose level (FG, mmol/l): =&lt;5.0; 5.1-5.5; 5.6-6.0 and 6.1-6.9 (pre-diabetic range) and &gt;=7.0 (new-onset diabetes) and established diabetes, and trends between the groups were assessed. Few and inconsistent associations were observed in the AGES-RS cohort and in the elderly group in the MPP-RES cohort between increasing glucometabolic impairment and measures of LVDD. These observations are in contrast to previous findings in younger subjects as well as the present findings in the middle-aged group in the MPP-RES cohort, where a significant association was found between increasing LVDD and increasing glucometabolic impairment. It was concluded that changes in LV diastolic function may be more related to age than glucose metabolism in elderly subjects.<br/><br>
<br/><br>
In Paper II possible associations between N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and FG as a continuous variable and in FG groups (as in Paper I) were assessed in the MPP-RES echocardiography subcohort. A positive correlation was found between Nt-proBNP and FG among middle-aged men. A positive correlation was also observed among elderly men, albeit non-significant. A non-significant negative correlation was observed among women in both age groups. The results indicate that caution should probably be exercised when interpreting Nt-proBNP values in subjects with impaired glucose metabolism. <br/><br>
<br/><br>
In Paper III the strength of the correlation between glucometabolic impairment, CVD risk factor burden and self-rated health (SRH), in middle-aged and elderly groups in the whole MPP-RES cohort (n=18,238) was compared. Correlations between increasing glucometabolic impairment and CVD risk factor burden and the proportion of subjects reporting poor SRH increased for both men and women in both age groups (p-trend &lt;0.0001 for all). The slope of the trend curve with increasing CVD risk factor burden was significantly steeper for elderly women than for elderly men (p-interaction=0.002). The slope of the trend curve for poor SRH was significantly steeper for middle-aged than for elderly men (p-interaction=0.005), while no difference was observed between the age groups in the women. These results indicate lifelong CVD risk factor clustering and poorer SRH with increased glucometabolic impairment, being somewhat more pronounced in elderly women than in elderly men.<br/><br>
<br/><br>
Finally, in Paper IV we examined whether the previously observed age-related reduction in excess CVD risk for diabetic compared to non-diabetic subjects also applies to pre-diabetic conditions. The MPP-RES cohort was followed for 4.1+/-1.3 years during which 1,296 CVD events occurred. Subjects were grouped by FG, gender and age, as previously. The hazard ratios for CVD events increased with increasing FG among middle-aged men and women. No comparable increase was observed among elderly subjects, where men with FG =&lt;5.0-6.9 and women with FG =&lt;5.0-6.0 had HRs close to 1.0. The B-coefficients for interaction between age groups and intergroup trends were -0.17 (unadjusted p=0.01) and -0.15 (fully adjusted p=0.03) for men, and -0.13 (p=0.27) for women (irrespective of adjustment). It was concluded that FG values within the upper pre-diabetic range conveyed less excess risk of CVD events among elderly than middle-aged men and women.},
  author       = {Leosdottir, Margrét},
  isbn         = {978-91-86871-78-9},
  issn         = {1652-8220},
  keyword      = {Age,cardiovascular disease,diabetes,echocardiography,gender,glucose,left ventricular function,Nt-proBNP,self-rated health},
  language     = {eng},
  pages        = {152},
  publisher    = {Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Age and gender differences in risk factor burden, myocardial dysfunction and cardiovascular events in relation to glucose metabolism},
  volume       = {2012:16},
  year         = {2012},
}