Browsing by Subject "Cardiovascular disease"

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  • Vuori, Matti A.; Harald, Kennet; Jula, Antti; Valsta, Liisa; Laatikainen, Tiina; Salomaa, Veikko; Tuomilehto, Jaakko; Jousilahti, Pekka; Niiranen, Teemu J. (2020)
    Aims: The objective was to evaluate whether sodium intake, assessed with the gold standard 24-h urinary collections, was related to long-term incidence of death, cardiovascular disease (CVD) and diabetes mellitus (DM). Methods:A cohort of 4630 individuals aged 25-64 years collected 24-h urine samples in 1979-2002 and were followed up to 14 years for the incidence of any CVD, coronary heart disease (CHD), stroke, heart failure (HF) and DM event, and death. Cox proportional hazards models were used to estimate the association between the baseline salt intake and incident events and adjusted for baseline age, body mass index, serum cholesterol, prevalent DM, and stratified by sex and cohort baseline year. Results: During the follow-up, we observed 423 deaths, 424 CVD events (288 CHD events, 142 strokes, 139 HF events) and 161 DM events. Compared with the highest quartile of salt intake, persons in the lowest quartile had a lower incidence of CVD (hazard ratio [HR] 0.70; 95% confidence interval [CI], 0.51-0.95,p = .02), CHD (HR 0.63 [95% CI 0.42-0.94],p = .02) and DM (HR 0.52 [95% CI 0.31-0.87],p = .01). The results were non-significant for mortality, HF, and stroke. Conclusion: High sodium intake is associated with an increased incidence of CVD and DM.
  • Zhu, Ruixin; Fogelholm, Mikael; Poppitt, Sally D.; Silvestre, Marta P.; Møller, Grith; Huttunen-Lenz, Maija; Stratton, Gareth; Sundvall, Jouko; Råman, Laura; Jalo, Elli; Taylor, Moira A.; Macdonald, Ian A.; Handjiev, Svetoslav; Handjieva-Darlenska, Teodora; Martinez, J. Alfredo; Muirhead, Roslyn; Brand-Miller, Jennie; Raben, Anne (2021)
    Plant-based diets are recommended by dietary guidelines. This secondary analysis aimed to assess longitudinal associations of an overall plant-based diet and specific plant foods with weight-loss maintenance and cardiometabolic risk factors. Longitudinal data on 710 participants (aged 26–70 years) with overweight or obesity and pre-diabetes from the 3-year weight-loss maintenance phase of the PREVIEW intervention were analyzed. Adherence to an overall plant-based diet was evaluated using a novel plant-based diet index, where all plant-based foods received positive scores and all animal-based foods received negative scores. After adjustment for potential confounders, linear mixed models with repeated measures showed that the plant-based diet index was inversely associated with weight regain, but not with cardiometabolic risk factors. Nut intake was inversely associated with regain of weight and fat mass and increments in total cholesterol and LDL cholesterol. Fruit intake was inversely associated with increments in diastolic blood pressure, total cholesterol, and LDL cholesterol. Vegetable intake was inversely associated with an increment in diastolic blood pressure and triglycerides and was positively associated with an increase in HDL cholesterol. All reported associations with cardiometabolic risk factors were independent of weight change. Long-term consumption of nuts, fruits, and vegetables may be beneficial for weight management and cardiometabolic health, whereas an overall plant-based diet may improve weight management only.
  • Strandberg, Timo E. (2022)
    The status of low‑density lipoprotein (LDL) cholesterol is strong as an essential cause of atherosclerotic vascular disease (ASCVD) and primary target of lipid lowering. Drugs affecting primarily LDL choles‑ terol through an increase of LDL receptor expression are the backbone of current therapy, and generic statins are generally safe, effective, and inexpensive drugs serving this purpose. Statins are indicated for practically all patients in secondary prevention, whereas treatment in primary prevention (healthy individuals) is based on a calculated 10‑year risk of ASCVD. At “borderline” (from 5% to “intermediate” (from 7.5% to for accurate assessment of the individual risk. The calculation of a lifetime risk instead of the 10‑year risk can be especially useful in younger people. More information about the benefits and risks of statins in primary prevention in older people (>70 years of age) will be provided by ongoing randomized and controlled trials (STAREE and PREVENTABLE). In this narrative review, I shall present recent advances in the use of statins in younger and older healthy people, and discuss their benefits and potential risks. I also raise a question whether with the current evidence base, most people in affluent societies would benefit from taking statins.
  • GBD 2015 Eastern Mediterranean Reg (2018)
    To report the burden of cardiovascular diseases (CVD) in the Eastern Mediterranean Region (EMR) during 1990-2015. We used the 2015 Global Burden of Disease study for estimates of mortality and disability-adjusted life years (DALYs) of different CVD in 22 countries of EMR. A total of 1.4 million CVD deaths (95% UI: 1.3-1.5) occurred in 2015 in the EMR, with the highest number of deaths in Pakistan (465,116) and the lowest number of deaths in Qatar (723). The age-standardized DALY rate per 100,000 decreased from 10,080 in 1990 to 8606 in 2015 (14.6% decrease). Afghanistan had the highest age-standardized DALY rate of CVD in both 1990 and 2015. Kuwait and Qatar had the lowest age-standardized DALY rates of CVD in 1990 and 2015, respectively. High blood pressure, high total cholesterol, and high body mass index were the leading risk factors for CVD. The age-standardized DALY rates in the EMR are considerably higher than the global average. These findings call for a comprehensive approach to prevent and control the burden of CVD in the region.
  • Olander, Rasmus F. W.; Litwin, Linda; Sundholm, Johnny K. M.; Sarkola, Taisto (2022)
    Studies examining the link between abnormal fetal growth and cardiac changes in childhood have presented conflicting results. We studied the effect of abnormal fetal growth on cardiac morphology and function during childhood, while controlling for body size, composition and postnatal factors. We report on the follow-up of 90 children (median age 5.81 years, IQR 5.67; 5.95) born appropriate for gestational age (AGA, N = 48), small for gestational age (SGA, N = 23), or large for gestational age (LGA, N = 19); SGA and LGA defined as birth weight Z-score < - 2 and > + 2, respectively. We examined the heart using echocardiography, including Doppler and strain imaging, in relation to anthropometrics, body composition, blood pressure, physical activity, and diet. Although groupwise differences in body size decreased during the first year after birth, LGA remained larger at follow-up, with higher lean body mass and BMI, while SGA were smaller. Slight changes in left ventricular diastolic function were present in SGA and LGA, with SGA showing increased mitral diastolic E- and A-wave peak flow velocities, and increased septal E/E ' ratio, and LGA showing larger left atrial volume adjusted for sex and lean body mass. In univariate analyses, lean body mass at follow-up was the strongest predictor of cardiac morphology. We found no groupwise differences at follow-up for ventricular sphericity, cardiac morphology adjusted for lean body mass and sex, or blood pressure, diet, or physical activity. Cardiac morphology is predicted by lean body mass during childhood, even in the setting of abnormal fetal growth. Our results are consistent with a limited effect of fetal programming on cardiac dimensions during childhood. Minor changes in diastolic function are present in both SGA and LGA children, however, the clinical significance of these changes at this stage is likely small.
  • Toppila, Iiro; Kysenius, Kai; Miettinen, Tatu; Lassenius, Mariann Ida; Lievonen, Juha; Anttila, Pekka (2022)
    Multiple myeloma (MM) patients are predominantly elderly with comorbidities that have an impact on patient mortality and treatment decisions. We previously reported the patient characteristics and overall survival outcomes of the Finnish MM cohort diagnosed between 2005 and 2016 in a nationwide retrospective registry study comprising 3,851 adults. Here, we report detailed comorbidity characteristics for this real-world Finnish MM population at cohort entry and during follow-up. Data on diagnoses and causes of death were obtained from Finnish healthcare data registries and interrogated using various multistate time-to-event models. In the year preceding MM diagnosis, comorbidities (as per Charlson Comorbidity Index definition) were recorded in 38.0% of the cohort, of which 27.9% presented with pre-existing cardiovascular disease (CVD) and 4.8% had suffered a major adverse cardiac event (MACE). At 2 years post-MM diagnosis, cumulative incidence for CVD and MACE more than doubled to 57.1% and 11.4%, respectively, and only 31.9% of the cohort remained CVD-free. Prevalent secondary malignancies were recorded in 16.8% of the patient population at MM diagnosis, with cumulative incidence increasing steadily to 27.5% at 2 years and 33% at 5 years post-diagnosis. The main cause of mortality attributed to MM, CVD, secondary malignancy, or other causes remained stable throughout the follow-up, at an average of 74.2%, 9.4%, 9.8%, and 6.5%, respectively. Prevalence of CVDs and secondary malignancies is high in Finnish patients at MM diagnosis, with older male patients suffering from higher MACE and mortality risk. Proper recording and management of comorbidities alongside novel treatments remain crucial for optimal MM management.
  • Framke, Elisabeth; Sorensen, Jeppe Karl; Andersen, Per Kragh; Svane-Petersen, Annemette Coop; Alexanderson, Kristina; Bonde, Jens Peter; Farrants, Kristin; Flachs, Esben Meulengracht; Hanson, Linda L. Magnusson; Nyberg, Solja T.; Villadsen, Ebbe; Kivimäki, Mika; Rugulies, Reiner; Madsen, Ida E. H. (2020)
    Aims We examined the extent to which associations between education and cardiovascular disease (CVD) morbidity and mortality are attributable to income and work stress. Methods and results We included all employed Danish residents aged 30-59 years in 2000. Cardiovascular disease morbidity analyses included 1 638 270 individuals, free of cardiometabolic disease (CVD or diabetes). Mortality analyses included 41 944 individuals with cardiometabolic disease. We assessed education and income annually from population registers and work stress, defined as job strain, with a job-exposure matrix. Outcomes were ascertained until 2014 from health registers and risk was estimated using Cox regression. During 10 957 399 (men) and 10 776 516 person-years (women), we identified 51 585 and 24 075 incident CVD cases, respectively. For men with low education, risk of CVD was 1.62 [95% confidence interval (CI) 1.58-1.66] before and 1.46 (95% CI 1.42-1.50) after adjustment for income and job strain (25% reduction). In women, estimates were 1.66 (95% CI 1.61-1.72) and 1.53 (95% CI 1.47-1.58) (21% reduction). Of individuals with cardiometabolic disease, 1736 men (362 234 personyears) and 341 women (179 402 person-years) died from CVD. Education predicted CVD mortality in both sexes. Estimates were reduced with 54% (men) and 33% (women) after adjustment for income and job strain. Conclusion Low education predicted incident CVD in initially healthy individuals and CVD mortality in individuals with prevalent cardiometabolic disease. In men with cardiometabolic disease, income and job strain explained half of the higher CVD mortality in the tow education group. In healthy men and in women regardless of cardiometabolic disease, these factors explained 21-33% of the higher CVD morbidity and mortality.
  • Vähämurto, Lauri; Pahkala, Katja; Magnussen, Costan G.; Hutri-Kähönen, Nina; Kähönen, Mika; Laitinen, Tomi; Taittonen, Leena; Tossavainen, Päivi; Lehtimäki, Terho; Jokinen, Eero; Telama, Risto; Rönnemaa, Tapani; Viikari, Jorma; Juonala, Markus; Raitakari, Olli T. (2019)
    Background and aims: In the 1960s and 1970s, Finland, mortality due to coronary heart disease (CHD) was over 30% higher among Finns residing in the east of the country compared with those residing in the west. Today, CHD mortality remains 20% higher among eastern Finns. The higher incidence of CHD mortality among eastern Finns has largely been explained by higher risk factor levels. Using a unique longitudinal cohort, we aimed to determine if participants who resided in eastern Finland during childhood had higher CHD risk factors in adulthood and from childhood to adulthood. Methods: The study population included 2063 participants of the Cardiovascular Risk in Young Finns Study, born during the period 1962-1977, with risk factor data available from baseline (1980) when participants were aged 3-18 years, and had risk factor data collected again in adulthood (2011) when aged 34-49 years. Results: Adult CHD risk factor profile was similar for those who resided in eastern or western Finland in childhood. Over life-course from 1980 to 2011, those subjects with childhood residency in eastern Finland had, on average, higher systolic (p = 0.006) and diastolic (p = 0.0009) blood pressures, total (p = 0.01) and LDLcholesterol (p = 0.01), triglycerides (p = 0.04), apoB (p = 0.02), and serum glucose (p Conclusions: Our sample of adult Finns aged 34-49 years had a similar CHD risk factor profile irrespective of whether they resided in eastern or western Finland during their childhood. However, when considering participants risk factor profiles over a 31-year period, those who resided in eastern Finland in childhood were associated with a less favorable CHD risk factor profile than those who resided in western Finland in childhood. The observed differences suggest that future CHD mortality might remain higher in eastern Finland compared with western Finland.
  • Iozzo, Patricia; Holmes, Megan; Schmidt, Mathias V.; Cirulli, Francesca; Guzzardi, Maria Angela; Berry, Alessandra; Balsevich, Georgia; Andreassi, Maria Grazia; Wesselink, Jan-Jaap; Liistro, Tiziana; Gomez-Puertas, Paulino; Eriksson, Johan G.; Seckl, Jonathan (2014)
  • Vornanen, Marleena; Konttinen, Hanna; Peltonen, Markku; Haukkala, Ari (2021)
    Background Perceived disease risk may reflect actual risk indicators and/or motivation to change lifestyle. Yet, few longitudinal studies have assessed how perceived risk relates to risk indicators among different disease risk groups. We examined in a 5-year follow-up, whether perceived risks of diabetes and cardiovascular disease predicted physical activity, body mass index (BMI kg/m(2)), and blood glucose level, or the reverse. We examined further whether perceived risk, self-efficacy, and outcome beliefs together predicted changes in these risk indicators. Method Participants were high diabetes risk participants (N = 432) and low/moderate-risk participants (N = 477) from the national FINRISK 2002 study who were followed up in 2007. Both study phases included questionnaires and health examinations with individual feedback letters. Data were analyzed using gender- and age-adjusted structural equation models. Results In cross-lagged autoregressive models, perceived risks were not found to predict 5-year changes in physical activity, BMI, or 2-h glucose. In contrast, higher BMI and 2-h glucose predicted 5-year increases in perceived risks (beta-values 0.07-0.15,P-values <0.001-0.138). These associations were similar among high- and low/moderate-risk samples. In further structural equation models, higher self-efficacy predicted increased physical activity among both samples (beta-values 0.10-0.16,P-values 0.005-0.034). Higher outcome beliefs predicted lower BMI among the low/moderate-risk sample (beta-values - 0.04 to - 0.05,P-values 0.008-0.011). Conclusion Perceived risk of chronic disease rather follows risk indicators than predicts long-term lifestyle changes. To promote sustained lifestyle changes, future intervention studies need to examine the best ways to combine risk feedback with efficient behavior change techniques.
  • FinnDiane Study Grp (2018)
    Aims/hypothesisThe aim of this study was to assess the potential dose-dependent effects of smoking on the risk of CHD, heart failure and stroke in individuals with type 1 diabetes.MethodsThe study included 4506 individuals with type 1 diabetes who were participating in the Finnish Diabetic Nephropathy (FinnDiane) study. Intensity of smoking was estimated by packs per day and cumulative smoking by pack-years. Cox regression analyses were used to estimate the risk of incident CHD, heart failure or stroke during follow-up.ResultsOne pack per day significantly increased the risk of incident CHD in current smokers compared with never smokers (HR 1.45 [95% CI 1.15, 1.84]), after adjustment for age, sex, HbA(1c), hypertension, duration of diabetes and BMI. The risk of CHD in former smokers was similar to the risk in never smokers. The risk of incident heart failure was 1.43 (95% CI 1.03, 1.97) in current smokers per one pack per day and 1.37 (95% CI 1.05, 1.77) in former smokers, while the risk of incident stroke was 1.70 (95% CI 1.26, 2.29) and 1.49 (95% CI 1.14, 1.93), respectively. After further adjustments for lipids, however, the difference in the risk of heart failure in current and former smokers was no longer significant. Cumulative smoking data were similar to smoking intensity data.Conclusions/interpretationThere is a dose-dependent association between smoking and cardiovascular disease in individuals with type 1 diabetes. In men in particular, the risk of incident stroke remains high even after smoking cessation and is increased in current and former smokers independently of other risk factors.
  • Lehtisalo, Jenni; Rusanen, Minna; Solomon, Alina; Antikainen, Riitta; Laatikainen, Tiina; Peltonen, Markku; Strandberg, Timo; Tuomilehto, Jaakko; Soininen, Hilkka; Kivipelto, Miia; Ngandu, Tiia (2022)
    Aims Joint prevention of cardiovascular disease (CVD) and dementia could reduce the burden of both conditions. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated a beneficial effect on cognition (primary outcome) and we assessed the effect of this lifestyle intervention on incident CVD (pre-specified secondary outcome). Methods and results FINGER enrolled 1259 individuals aged 60-77 years (ClinicalTrials.gov NCT01041989). They were randomized (1:1) to a 2-year multi-domain intervention with diet, physical and cognitive activity, and vascular monitoring (n = 631), or general health advice (n = 628). National registries provided data on CVD including stroke, transient ischaemic attack (TIA), or coronary heart event. During an average of 7.4 years, 229 participants (18%) had at least one CVD diagnosis: 107 in the intervention group and 122 in the control group. The incidence of cerebrovascular events was lower in the intervention than the control group: hazard ratio (HR) for combined stroke/TIA was 0.71 [95% confidence interval (CI): 0.51-0.99] after adjusting for background characteristics. Hazard ratio for coronary events was 0.84 (CI: 0.56-1.26) and total CVD events 0.80 (95% CI: 0.61-1.04). Among those with history of CVD (n = 145), the incidence of both total CVD events (HR: 0.50, 95% CI: 0.28-0.90) and stroke/TIA (HR: 0.40, 95% CI: 0.20-0.81) was lower in the intervention than the control group. Conclusion A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those who had history of CVD. Key question Can a 2-year multi-domain lifestyle intervention, primarily designed for prevention of cognitive impairment, prevent new cardiovascular events among older adults over an extended follow-up? Key finding Among the 1259 participants aged 60-77 years, the intervention resulted in 13-20% lower cardiovascular disease (CVD) event rates (unadjusted and adjusted analyses), but with large degree of uncertainty. Cerebrovascular event rates were lower but for total CVD only among those with earlier CVD events. Take-home message A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those with a history of CVD.
  • Ray, Kausik K.; Haq, Inaam; Bilitou, Aikaterini; Aguiar, Carlos; Arca, Marcello; Connolly, Derek L.; Eriksson, Mats; Ferrières, Jean; Hildebrandt, Per; Laufs, Ulrich; Mostaza, Jose M.; Nanchen, David; Rietzschel, Ernst; Strandberg, Timo; Toplak, Hermann; Visseren, Frank L.J.; Catapano, Alberico L. (2021)
    Background and aims: Clinical practice before 2019 suggests a substantial proportion of high and very high CV risk patients taking lipid-lowering therapy (LLT) would not achieve the new LDL-C goals recommended in the 2019 ESC/EAS guidelines (<70 and < 55 mg/dL, respectively). To what extent practice has changed since the last ESC/EAS guideline update is uncertain, and quantification of remaining implementation gaps may inform health policy. Methods: The SANTORINI study is a multinational, multicentre, prospective, observational, non-interventional study documenting patient data at baseline (enrolment) and at 12-month follow-up. The study recruited 9606 patients ≥18 years of age with high and very high CV risk (as assigned by the investigators) requiring LLT, with no formal patient or comparator groups. The primary objective is to document, in the real-world setting, the effectiveness of current treatment modalities in managing plasma levels of LDL-C in high- and very high-risk patients requiring LLT. Key secondary effectiveness objectives include documenting the relationship between LLT and levels of other plasma lipids, high-sensitivity C-reactive protein (hsCRP) and overall predicted CV risk over one year. Health economics and patient-relevant parameters will also be assessed. Conclusions: The SANTORINI study, which commenced after the 2019 ESC/EAS guidelines were published, is ideally placed to provide important contemporary insights into the evolving management of LLT in Europe and highlight factors contributing to the low levels of LDL-C goal achievement among high and very high CV risk patients. It is hoped the findings will help enhance patient management and reduce the burden of ASCVD in Europe.
  • Antikainen, Anni A. V.; Sandholm, Niina; Tregouet, David-Alexandre; Charmet, Romain; McKnight, Amy Jayne; Ahluwalia, Tarunveer S.; Syreeni, Anna; Valo, Erkka; Forsblom, Carol; Gordin, Daniel; Harjutsalo, Valma; Hadjadj, Samy; Maxwell, Alexander P.; Rossing, Peter; Groop, Per-Henrik (2021)
    Aims Diabetes is a known risk factor for coronary artery disease (CAD). There is accumulating evidence that CAD pathogenesis differs for individuals with type 1 diabetes (T1D). However, the genetic background has not been extensively studied. We aimed to discover genetic loci increasing CAD susceptibility, especially in T1D, to examine the function of these discoveries and to study the role of the known risk loci in T1D. Methods and results We performed the largest genome-wide association study to date for CAD in T1D, comprising 4869 individuals with T1D (cases/controls: 941/3928). Two loci reached genome-wide significance, rs1970112 in CDKN2B-AS1 [odds ratio (OR) =1.32, P = 1.50 x 10(-8)], and rs6055069 on DEFB127 promoter (OR= 4.17, P= 2.35 x 10(-9)), with consistent results in survival analysis. The CDKN2B-AS1 variant replicated (P = 0.04) when adjusted for diabetic kidney disease in three additional T1D cohorts (cases/controls: 434/3123). Furthermore, we explored the function of the lead discoveries with a cardio-phenome-wide analysis. Among the eight suggestive loci (P <1 x 10(-6)), rs70962766 near B3GNT2 associated with central blood pressure, rs1344228 near CNTNAP5 with intima media thickness, and rs2112481 on GRAMD2B promoter with serum leucocyte concentration. Finally, we calculated genetic risk scores for individuals with T1D with the known susceptibility loci. General population risk variants were modestly but significantly associated with CAD also in T1D (P=4.21 x 10(-7)). Conclusion While general population CAD risk loci had limited effect on the risk in T1D, for the first time, variants at the CDKN2B-AS1 locus were robustly associated with CAD in individuals with T1D. The novel finding on beta-defensin DEFB127 promoter provides a link between diabetes, infection susceptibility, and CAD, although pending on future confirmation. [GRAPHICS] .
  • Korpijaakko, Cedric A.; Eriksson, Mia D.; Wasenius, Niko S.; Klemetti, Miira M.; Teramo, Kari; Kautiainen, Hannu; Eriksson, Johan G.; Laine, Merja K. (2022)
    Background Offspring of mothers with type 1 diabetes have an increased risk for acquiring early onset cardiovascular disease (CVD). Arterial stiffness, measured as pulse wave velocity (PWV), is a non-invasive biomarker for CVD risk assessment. Our aim is to determine whether PWV is increased in young adult offspring of mothers with type 1 diabetes. Methods This is a case-control study carried out in the hospital district of Helsinki and Uusimaa, Finland. 75 offspring of mothers with type 1 diabetes (cases) and 84 offspring of mothers without diabetes (controls), aged 18-23 years, were enrolled in this study. All participants attended clinical assessments, including questionnaires and laboratory tests. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and PWV ratio were measured from each participant using the Complior Analyse mechanotransducer (Alam Medical, France). Student's t-test and chi-squared test were used to assess differences between the groups. Stata 17.0, StataCorp LP (College Station, TX, USA) statistical package was used for the analysis. Results We did not observe any differences in conventional CVD risk factors: systolic blood pressure, LDL, Hb(A1c), and smoking between cases and controls. We detected higher cfPWV in cases 6.5 (SD +/- 1.2) m/s than in controls 6.2 (SD +/- 0.7) m/s, p = 0.049, after adjustments for BMI, smoking, mean arterial pressure, height, and pulse rate was made. We did not observe any difference between cases and controls regarding crPWV or PWV ratio. Additionally, we detected no sex differences. Conclusions We report a novel finding of signs of increased arterial stiffness already in young adult offspring of mothers with type 1 diabetes compared to matched offspring of mothers without diabetes. Our finding suggests that exposure to an adverse intrauterine environment of type 1 diabetes mothers may affect the vascular health of offspring already in young adulthood. Additional research within this topic is warranted.
  • Hanson, Linda L. Magnusson; Rod, Naja H.; Vahtera, Jussi; Virtanen, Marianna; Ferrie, Jane; Shipley, Martin; Kivimäki, Mika; Westerlund, Hugo (2020)
    Job insecurity has been linked to increased risk of coronary heart disease (CHD), but underlying mechanisms remain uncertain. Our aim was to assess the extent to which this association is mediated through life style, physiological, or psychological factors. A total of 3917 men and women free from CHD provided data on job insecurity in the Whitehall II cohort study in 1997-1999. The association between job insecurity and CHD was decomposed into a direct and indirect effect mediated through unhealthy behaviors (smoking, high alcohol consumption, physical inactivity), sleep disturbances, 'allostatic load', or psychological distress. The counterfactual analyses on psychological distress indicated a marginally significant association between job insecurity and incident CHD (hazard ratio (HR) 1.32; 95 % confidence interval (CI) 1.00-1.75). This association was decomposed into a direct (HR 1.22, 95 %CI 0.92-1.63) and indirect association (1.08, 95 %CI 1.01-1.15), suggesting that about 30 % of the total relationship was mediated by psychological distress. No mediation was indicated via health behaviors, sleep disturbances, or allostatic load, although job insecurity was related to disturbed sleep and C-reactive protein, which, in turn were associated with CHD. In conclusion, our results suggest that psychological distress may play a role in the relation between job insecurity and CHD.
  • Ference, Brian A.; Ginsberg, Henry N.; Graham, Ian; Ray, Kausik K.; Packard, Chris J.; Bruckert, Eric; Hegele, Robert A.; Krauss, Ronald M.; Raal, Frederick J.; Schunkert, Heribert; Watts, Gerald F.; Boren, Jan; Fazio, Sergio; Horton, Jay D.; Masana, Luis; Nicholls, Stephen J.; Nordestgaard, Borge G.; van de Sluis, Bart; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Landmesser, Ulf; Laufs, Ulrich; Wiklund, Olov; Stock, Jane K.; Chapman, M. John; Catapano, Alberico L. (2017)
    Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C. Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects. Conclusion Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.
  • Immonen, Tiia (Helsingin yliopisto, 2018)
    Matriksin metalloproteinaasi-8 on pääasiassa ihmisen yleisimpien valkosolujen eli neutrofiilien tuottama entsyymi. MMP-8 varastoidaan solunsisäisissä rakkuloissa ja se vaatii aktivaation toimiakseen. Sen tehtävänä on mahdollistaa neutrofiilien kulku tulehdusalueelle soluväliainetta muokkaamalla. Aktivoitu MMP-8 pilkkoo tyypin I kollageenia ja muita soluväliaineen rakenneosia. MMP-8 on mukana monissa fysiologisissa ja patologisissa prosesseissa, kuten haavan paranemisessa, sikiön kehityksessä, sekä monissa sairauksissa kuten parodontiitissa ja sydän- ja verisuonisairauksissa ja syövässä. Tämän kirjallisuuskatsauksen tarkoituksena on selvittää MMP-8:n molekyylibiologista taustaa, kuten rakennetta, toimintaa ja genetiikkaa sekä MMP-8:n hyödyntämistä diagnostiikassa. Tieteelliset artikkelit kirjallisuuskatsaukseen kerättiin PubMed – tietokannasta. MMP-8:n toiminnan ymmärtäminen on olennaista, sillä se on selkeä edistävä tekijä monissa vakavissa sairauksissa. Tieteellisiä tutkimuksia MMP-8:sta löytyy vuosikymmenien ajalta ja ne vahvistavat käsitystä MMP-8:n laaja-alaisesta toiminnasta. Molekyylin eritys ja aktivaatio on tarkasti säädeltyä ja rajoitettu lähinnä tulehdusalueille. MMP-8:n estäjänä voi toimia TIMP (tissue inhibitors of metalloproteinase) – proteiiniperheen lisäksi muun muassa tetrasykliini-ryhmään kuuluvat antibiootit, kuten doksisykliini. MMP-8:n genetiikan tutkimus on vasta aluillaan, mutta joitain yhteyksiä MMP-8:n geenin variaatioiden eli polymorfismien ja parodontiitin ja peri-implantiitin välillä on kyetty löytämään. Tutkijat ovatkin kiinnostuneet MMP-8:sta diagnostisena apuvälineenä, mutta lisää tutkimusta aiheesta tarvitaan. MMP-8:aan liittyvää lisätutkimusta tarvitaan erityisesti, jotta elimistön eri nesteistä mitattavaa MMP-8-konsentraatiota voidaan soveltaa laajamittaisesti kliiniseen käyttöön eri tautitiloissa.
  • Coleman, Ruth L; Scott, Charles A B; Lang, Zhihui; Bethel, M. A; Tuomilehto, Jaakko; Holman, Rury R (BioMed Central, 2019)
    Abstract Background Alpha-glucosidase inhibitors (AGIs) have been shown to reduce incident type 2 diabetes but their impact on cardiovascular (CV) disease remains controversial. We sought to identify the overall impact of AGIs with respect to incident type 2 diabetes in individuals with impaired glucose tolerance (IGT), and CV outcomes in those with IGT or type 2 diabetes. Methods We used PubMed and SCOPUS to identify randomized controlled trials reporting the incidence of type 2 diabetes and/or CV outcomes that had compared AGIs with placebo in populations with IGT or type 2 diabetes, with or without established CV disease. Eligible studies were required to have ≥ 500 participants and/or ≥ 100 endpoints of interest. Meta-analyses of available trial data were performed using random effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes and CV outcomes. Results Of ten trials identified, three met our inclusion criteria for incident type 2 diabetes and four were eligible for CV outcomes. The overall HR (95% CI) comparing AGI with placebo for incident type 2 diabetes was 0.77 (0.67–0.88), p < 0.0001, and for CV outcomes was 0.98 (0.89–1.10), p = 0.85. There was little to no heterogeneity between studies, with I2 values of 0.03% (p = 0.43) and 0% (p = 0.79) for the two outcomes respectively. Conclusions Allocation of people with IGT to an AGI significantly reduced their risk of incident type 2 diabetes by 23%, whereas in those with IGT or type 2 diabetes the impact on CV outcomes was neutral.
  • Coleman, Ruth L.; Scott, Charles A. B.; Lang, Zhihui; Bethel, M. Angelyn; Tuomilehto, Jaakko; Holman, Rury R. (2019)
    Background Alpha-glucosidase inhibitors (AGIs) have been shown to reduce incident type 2 diabetes but their impact on cardiovascular (CV) disease remains controversial. We sought to identify the overall impact of AGIs with respect to incident type 2 diabetes in individuals with impaired glucose tolerance (IGT), and CV outcomes in those with IGT or type 2 diabetes. Methods We used PubMed and SCOPUS to identify randomized controlled trials reporting the incidence of type 2 diabetes and/or CV outcomes that had compared AGIs with placebo in populations with IGT or type 2 diabetes, with or without established CV disease. Eligible studies were required to have >= 500 participants and/or >= 100 endpoints of interest. Meta-analyses of available trial data were performed using random effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes and CV outcomes. Results Of ten trials identified, three met our inclusion criteria for incident type 2 diabetes and four were eligible for CV outcomes. The overall HR (95% CI) comparing AGI with placebo for incident type 2 diabetes was 0.77 (0.67-0.88), p <0.0001, and for CV outcomes was 0.98 (0.89-1.10), p = 0.85. There was little to no heterogeneity between studies, with I-2 values of 0.03% (p = 0.43) and 0% (p = 0.79) for the two outcomes respectively. Conclusions Allocation of people with IGT to an AGI significantly reduced their risk of incident type 2 diabetes by 23%, whereas in those with IGT or type 2 diabetes the impact on CV outcomes was neutral.