The role of cortisol in ischemic heart disease, ischemic stroke, type 2 diabetes, and cardiovascular disease risk factors: a bi-directional Mendelian randomization study

Abstract Background Cortisol, a steroid hormone frequently used as a biomarker of stress, is associated with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). To clarify whether cortisol causes these outcomes, we assessed the role of cortisol in ischemic heart disease (IHD), ischemic stroke, T2DM, and CVD risk factors using a bi-directional Mendelian randomization (MR) study. Methods Single nucleotide polymorphisms (SNPs) strongly (P < 5 × 10−6) and independently (r2 < 0.001) predicting cortisol were obtained from the CORtisol NETwork (CORNET) consortium (n = 12,597) and two metabolomics genome-wide association studies (GWAS) (n = 7824 and n = 2049). They were applied to GWAS of the primary outcomes (IHD, ischemic stroke and T2DM) and secondary outcomes (adiposity, glycemic traits, blood pressure and lipids) to obtain estimates using inverse variance weighting, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. Conversely, SNPs predicting IHD, ischemic stroke, and T2DM were applied to the cortisol GWAS. Results Genetically predicted cortisol (based on 6 SNPs from CORNET; F-statistic = 28.3) was not associated with IHD (odds ratio (OR) 0.98 per 1 unit increase in log-transformed cortisol, 95% confidence interval (CI) 0.93–1.03), ischemic stroke (0.99, 95% CI 0.91–1.08), T2DM (1.00, 95% CI 0.96–1.04), or CVD risk factors. Genetically predicted IHD, ischemic stroke, and T2DM were not associated with cortisol. Conclusions Contrary to observational studies, genetically predicted cortisol was unrelated to IHD, ischemic stroke, T2DM, or CVD risk factors, or vice versa. Our MR results find no evidence that cortisol plays a role in cardiovascular risk, casting doubts on the cortisol-related pathway, although replication is warranted.

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Determining the Cardiovascular Disease Risk Factor Knowledge and Related Factors Among Adults With Type 2 Diabetes Mellitus

Clinical Nursing Research ◽

10.1177/10547738211046441 ◽

2021 ◽

pp. 105477382110464

Author(s):

Emine Karaman ◽

Aslı Kalkım ◽

Banu Pınar Şarer Yürekli

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Related Factors

In this study was to determine knowledge of cardiovascular disease (CVD) risk factors and to explore related factors among adults with type 2 diabetes mellitus (DM) who have not been diagnosed with CVD. This descriptive study was conducted with 175 adults. Data were collected individual identification form and Cardiovascular Disease Risk Factors Knowledge Level (CARRF-KL) scale. A negative correlation was found between age and CARRF-KL score. A significant difference was found between educational status and CARRF-KL score. The individuals described their health status as good, managed their condition with diet and exercise, received information from nurses, adults with DM in their family and those with no DM complications had significantly higher scores in CARRF-KL. The knowledge of an individual with DM about CVD risk factors should be assessed, CVD risks should be identified at an early stage, and individuals at risk should be subjected to screening.

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Physical activity less than the recommended amount may prevent the onset of major biological risk factors for cardiovascular disease: a cohort study of 198 919 adults

British Journal of Sports Medicine ◽

10.1136/bjsports-2018-099740 ◽

2018 ◽

Vol 54 (4) ◽

pp. 238-244 ◽

Cited By ~ 1

Author(s):

David Martinez-Gomez ◽

Irene Esteban-Cornejo ◽

Esther Lopez-Garcia ◽

Esther García-Esquinas ◽

Kabir P Sadarangani ◽

...

Keyword(s):

Physical Activity ◽

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Highly Active ◽

Atherogenic Dyslipidaemia

ObjectivesWe examined the dose–response relationship between physical activity (PA) and incidence of cardiovascular disease (CVD) risk factors in adults in Taiwan.MethodsThis study included 1 98 919 participants, aged 18–97 years, free of CVD, cancer and diabetes at baseline (1997–2013), who were followed until 2016. At baseline, participants were classified into five PA levels: inactive’ (0 metabolic equivalent of task (MET)-h/week), ‘lower insufficiently active’ (0.1–3.75 MET-h/week), ‘upper insufficiently active’ (3.75–7.49 MET-h/week), ‘active’ (7.5–14.99 MET-h/week) and ‘highly active’ (≥15 MET-h/week]. CVD risk factors were assessed at baseline and at follow-up by physical examination and laboratory tests. Analyses were performed with Cox regression and adjusted for the main confounders.ResultsDuring a mean follow-up of 6.0±4.5 years (range 0.5–19 years), 20 447 individuals developed obesity, 19 619 hypertension, 21 592 hypercholesterolaemia, 14 164 atherogenic dyslipidaemia, 24 275 metabolic syndrome and 8548 type 2 diabetes. Compared with inactive participants, those in the upper insufficiently active (but not active) category had a lower risk of obesity (HR 0.92; 95% CI 0.88 to 0.95), atherogenic dyslipidaemia (0.96; 0.90 to 0.99), metabolic syndrome (0.95; 0.92 to 0.99) and type 2 diabetes (0.91; 0.86 to 0.97). Only highly active individuals showed a lower incidence of CVD risk factors than their upper insufficiently active counterparts.ConclusionCompared with being inactive, doing half the recommended amount of PA is associated with a lower incidence of several common biological CVD risk factors. Given these benefits, half the recommended amount of PA is an evidence based target for inactive adults.

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Abstract 013: High Prevalence and Rapid Increase of Cardiovascular Disease Risk Factors in Youth with Type 2 Diabetes: The TODAY Study Group

Circulation ◽

10.1161/circ.127.suppl_12.a013 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Fida Bacha ◽

Samuel S Gidding ◽

Sonia Caprio ◽

Ruth Weinstock ◽

Jane Lynch ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Glycemic Control ◽

Hemoglobin A1c ◽

Male Gender ◽

High Risk Population ◽

Cvd Risk Factors ◽

Cvd Risk

Background The natural history of type 2 diabetes (T2D) in youth appears to differ from that in adults in that almost half of T2D youth in the “Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY)” study had a rapid decline in beta cell function. The rate of change in risk for cardiovascular disease (CVD) in youth with T2D is not known. We tested the hypothesis that CVD risk factors are highly prevalent and rapidly progress over time in youth with T2D using longitudinal assessments of hypertension (HT), microalbuminuria (MA) and dyslipidemia obtained during the TODAY clinical trial of adolescents with recent onset T2D. Methods A cohort of 699 adolescents, aged 10-17 years, <2 years duration of T2D, body mass index (BMI) ≥85th percentile, Hemoglobin A1c (A1c) ≤8% on metformin therapy were randomized to metformin alone, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention and followed over an average of 3.9 years. (range 2-6.5 years). Primary outcome was loss of glycemic control. Quarterly BP and annual MA were monitored with initiation and titration of therapy (ACE inhibitor) to maintain BP <130/80 or <95th percentile for age, gender, and height and MA <30 mcg/mg. Statin drugs were begun for LDL cholesterol (LDLC) ≥130 mg/dL or triglycerides ≥300 mg/dL. Change in the prevalence of CVD risk factors was examined accounting for the effect of treatment group, time, glycemic control, gender, and race-ethnicity. Results In this cohort, 319 (45•6%) reached primary glycemic outcome. HTN was observed in 11•6% of subjects at baseline and 33•8% by end of study (average follow-up 3•9 years). MA was found in 6•3% at baseline and rose to 16•6% at study end. Participants with LDLC ≥130 mg/dL or statin use increased from 4.5% to 10.7%. Male gender and higher BMI significantly increased the risk for HTN. Higher levels of hemoglobin A1c correlated with the risk of developing MA and dyslipidemia. Conclusion The prevalence of CVD risk factors increased rapidly among adolescents with T2D regardless of diabetes treatment. The greatest risk for HTN was male gender and higher BMI. The risk for microalbuminuria and worsening of dyslipidemia was related to glycemic control. Measures to address CVD risk are needed early in the disease course in this high risk population.

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Cardiovascular Disease Related Proteomic Biomarkers of Alcohol Consumption

10.1101/2020.10.17.332197 ◽

2020 ◽

Author(s):

Xianbang Sun ◽

Jennifer E. Ho ◽

He Gao ◽

Evangelos Evangelou ◽

Chen Yao ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Alcohol Consumption ◽

Lower Risk ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Associated Proteins ◽

Triangular Relationships

AbstractThe relationship between alcohol consumption, circulating proteins, and cardiovascular disease (CVD) risk has not been well studied. We performed association analyses of alcohol consumption with three CVD risk factors and 71 CVD-related circulating proteins measured in 6,745 Framingham Heart Study participants (mean age, 49 years; 53% women). We found that an increase in alcohol consumption was associated with a higher risk of incident hypertension (P=7.2E-3) but a lower risk of incident obesity (P=5.7E-4) and type 2 diabetes (P=1.4E-5) in a 14-year of follow-up. Using independent discovery (n=4,348) and validation (n=2,397) samples, we identified 20 alcohol-associated proteins (FDR<0.05 in discovery and P<0.05/n in validation), with majority (18 of 20 proteins) inversely associated with alcohol consumption. The alcohol-protein associations remained similar after removing heavy drinkers. Four proteins demonstrated consistent triangular relationships, as expected, with alcohol consumption and CVD risk factors. For example, a greater level of APOA1, which was associated with a higher alcohol consumption (P=1.2E-65), was associated with a lower risk of type 2 diabetes (P=3.1E-5). However, several others showed inconsistent triangular relationships, e.g., a greater level of GDF15, which was associated with a lower alcohol consumption (P=1.0E-13), was associated with an increased risk of hypertension (P=2.4E-4). In conclusion, we identified 20 alcohol-associated proteins and demonstrated complex relationships between alcohol consumption, circulating proteins and CVD risk factors. Future studies with integration of more proteomic markers and larger sample size are warranted to unravel the complex relationship between alcohol consumption and CVD risk.

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Diabetic Polyneuropathy Early in Type 2 Diabetes Is Associated With Higher Incidence Rate of Cardiovascular Disease: Results From Two Danish Cohort Studies

10.2337/figshare.14453349.v1 ◽

2021 ◽

Author(s):

Lasse Bjerg ◽

Sia K Nicolaisen ◽

Diana H Christensen ◽

Jens S Nielsen ◽

Signe T Andersen ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Incidence Rate ◽

Diabetic Polyneuropathy ◽

Diabetes Diagnosis ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Rate Ratios

Objective Symptoms indicative of diabetic polyneuropathy (DPN) early in type 2 diabetes may act as a marker for cardiovascular disease (CVD) and death. Research Design and Methods We linked data from two Danish type 2 diabetes cohorts, ADDITION-Denmark and DD2, to national healthcare registers. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was completed at diabetes diagnosis in ADDITION-Denmark and at a median of 4.6 years after diagnosis of diabetes in DD2. An MNSIq score ≥ 4 was considered as indicative of DPN. Using Poisson regressions, we computed incidence rate ratios of CVD and all-cause mortality comparing MNSIq scores ≥ 4 with scores < 4. Analyses were adjusted for a range of established CVD risk factors. Results In total, 1,445 (ADDITION-Denmark) and 5,028 (DD2) individuals were included in the study. Compared with MNSIq scores < 4, MNSIq scores ≥ 4 were associated with higher incidence rate of CVD, with incidence rate ratios (IRRs) of 1.79 [95% confidence interval (CI) 1.38-2.31] in ADDITION-Denmark, 1.57 (CI: 1.27-1.94) in the DD2, and a combined IRR of 1.65 (CI: 1.41-1.95) in a fixed-effect meta-analysis. MNSIq scores ≥ 4 did not associate with mortality; combined mortality rate ratio 1.11 (CI: 0.83-1.48). Conclusions The MNSIq may be a tool to identify a subgroup within individuals with newly diagnosed type 2 diabetes who has a high incidence rate of subsequent CVD. MNSIq scores ≥ 4, indicating DPN, were associated with a markedly higher incidence rate of CVD, beyond that conferred by established CVD risk factors.

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Diabetic Polyneuropathy Early in Type 2 Diabetes Is Associated With Higher Incidence Rate of Cardiovascular Disease: Results From Two Danish Cohort Studies

10.2337/figshare.14453349 ◽

2021 ◽

Author(s):

Lasse Bjerg ◽

Sia K Nicolaisen ◽

Diana H Christensen ◽

Jens S Nielsen ◽

Signe T Andersen ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Incidence Rate ◽

Diabetic Polyneuropathy ◽

Diabetes Diagnosis ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Rate Ratios

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High Sensitivity C-Reactive Protein as Atherogenic Marker Among Type 2 Diabetes

European Scientific Journal ESJ ◽

10.19044/esj.2017.v13n33p403 ◽

2017 ◽

Vol 13 (33) ◽

pp. 403

Author(s):

Abdelmarouf H. Mohieldein ◽

Marghoob Hasan ◽

Mahmoud I. El-Habiby

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Diabetic Patients ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Vascular Events ◽

Apo B ◽

Hs Crp

Background: People with type 2 diabetes are threefold affected by cardiovascular disease (CVD) compared with non-diabetics. Many studies reported the absence of traditional CVD risk factors in a substantial portion of individuals experiencing clinical vascular events. Novel risk markers for CVD are often said to add independent predictive value for risk prediction. Objective: In the present study we evaluated different CVD risk factors based on highsensitivity C-reactive (hs- CRP) protein quartiles among diabetics and nondiabetics population. Methods: In this population- based cross- sectional study, we recruited a total of onehundred and nine participants (64 type 2 diabetics and 45 healthy controls). Venous blood sample collected from each subject. Body weight and height were measured and body mass index (BMI) was calculated. Biochemical analytes were measured according to standard procedures. Data analyzed using SPSS software. Results: Mean serum hs-CRP levels were significantly higher among diabetics (2.3 mg/l) compared to controls (1.8 mg/l; P = 0.019). Moreover, the 3rd & 4th quartiles of hs-CRP were characterized by more frequency of diabetes as well as hypertension. The percent of participants with diabetes or hypertension seemed positively related to hs CRP concentrations. Lipid profile analysis revealed the highest levels of LDL-C and Apo B in 4th quartile hs-CRP. In addition, participants in the 4th quartile hs-CRP were characterized by the highest age, BMI, plasma glucose. However, there was European Scientific Journal November 2017 edition Vol.13, No.33 ISSN: 1857 – 7881 (Print) e - ISSN 1857- 7431 404 no clear association between levels of hs-CRP and the HbA1c, TC, TG, HDL-C, and Apo A1. Conclusion: Measurement of hs-CRP in diabetic patients might provide useful information for development of atherosclerosis and cardiovascular disease and help in early intervention.

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Association between intake of fish and shellfish and omega‐3 (n‐3) fatty acids and cardiovascular disease (CVD) risk factors in middle‐aged female with type 2 diabetes (T2D). (LB343)

The FASEB Journal ◽

10.1096/fasebj.28.1_supplement.lb343 ◽

2014 ◽

Vol 28 (S1) ◽

Author(s):

Seokyung Park ◽

Eun Jung Lee ◽

Soyeon Kim ◽

Won Jang ◽

Hyesook Kim ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Fatty Acids ◽

Omega 3 ◽

Cvd Risk Factors ◽

Middle Aged ◽

Cvd Risk ◽

Fish And Shellfish

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South Asians and Anglo Australians with heart disease in Australia

Australian Health Review ◽

10.1071/ah14254 ◽

2015 ◽

Vol 39 (5) ◽

pp. 568 ◽

Cited By ~ 2

Author(s):

Sabrina Gupta ◽

Rosalie Aroni ◽

Siobhan Lockwood ◽

Indra Jayasuriya ◽

Helena Teede

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Heart Disease ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

South Asians ◽

Gensini Score ◽

Cvd Risk Factors ◽

Cvd Risk

Objectives The aim of the present study was to determine cardiovascular disease (CVD) risk factors and compare presentation and severity of ischaemic heart disease (IHD) among South Asians (SAs) and Anglo Australians (AAs). Methods A retrospective clinical case audit was conducted at a public tertiary hospital. The study population included SA and AA patients hospitalised for IHD. Baseline characteristics, evidence of diabetes and other CVD risk factors were recorded. Angiography data were also included to determine severity, and these were assessed using a modified Gensini score. Results SAs had lower mean (± s.d.) age of IHD presentation that AAs (52 ± 9 vs 55 ± 9 years, respectively; P = 0.02), as well as a lower average body mass index (BMI; 26 ± 4 vs 29 ± 6 kg/m2, respectively; P = 0.005), but a higher prevalence of type 2 diabetes (57% vs 31%, respectively; P = 0.001). No significant differences were found in coronary angiography parameters. There were no significant differences in the median (interquartile range) Gensini score between SAs and AAs (43.5 (27–75) vs 44 (26.5–68.5), respectively), median vessel score (1 (1–2) vs 2 (1–3), respectively) or multivessel score (37% (33/89) vs 54% (22/41), respectively). Conclusions The findings show that in those with established IHD, cardiovascular risk factors, such as age at onset and BMI, differ between SAs and AAs and these differences should be considered in the prevention and management of IHD. What is known about the topic? There is much evidence on CVD and SAs, it being a leading cause of mortality and morbidity for this population both in their home countries and in countries they have migrated to. Studies conducted in Western nations other than Australia have suggested a difference in the risk profiles and presentations of CVD among SA migrants compared with the host populations in developed countries. Although this pattern of cardiovascular risk factors among SAs has been well documented, there is insufficient knowledge about this population, currently the largest population of incoming migrants, and CVD in the Australian setting. What does this paper add? This paper confirms that a similar pattern of CVD exists in Australia among SAs as does in other Western nations they have migrated to. The CVD pattern found in this population is that of an earlier age of onset at lower BMI compared with the host AA population, as well as a differing cardiovascular risk profile, with higher rates of type 2 diabetes and lower smoking rates. In addition, this study finds similar angiographic results for both the SAs and AAs; however, the SAs exhibit these similar angiographic patterns at younger ages. What are the implications for practitioners? SAs in Australia represent a high cardiovascular risk group and should be targeted for more aggressive screening at younger ages. Appropriate preventative strategies should also be considered bearing in mind the differing risk factors for this population, namely low BMI and high rates of type 2 diabetes. More intensive treatment strategies should also be regarded by practitioners. Importantly, both policy makers and health professionals must consider that all these strategies should be culturally targeted and tailored to this population and not assume a ‘one-size fits all’ approach.

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408Albuminuria as a predictor of incident ischemic stroke and myocardial infarction in patients with type 2 diabetes but without cardiovascular disease: A Danish cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz747.0103 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M V Fangel ◽

P B Nielsen ◽

J K Kristensen ◽

T B Larsen ◽

T F Overvad ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cohort Study ◽

Ischemic Stroke ◽

Cardiovascular Risk ◽

All Cause Mortality ◽

Patients With Diabetes

Abstract Background Risk stratification in patients with type 2 diabetes continues to be an important priority in the management of diabetes-related morbidity and mortality. International guidelines generally recognize patients with diabetes and cardiovascular disease as high-risk patients. Risk stratification is, however, more uncertain in diabetes patients without cardiovascular disease. Micro- and macroalbuminuria have previously been identified as predictors of cardiovascular events and mortality in general cohorts of diabetes patients. However, less is known about the predictive value of albuminuria in patients with diabetes but without established cardiovascular disease. Purpose We aimed to examine the association between albuminuria level and the risk of ischemic stroke, myocardial infarction, and all-cause mortality in patients with type 2 diabetes and without a diagnosis of cardiovascular disease. Methods We linked Danish nationwide registries to identify patients with type 2 diabetes and without cardiovascular disease from May 2005 through June 2015. Based on two consecutive measurements of the urinary albumin excretion rate or albumin-to-creatinine ratio patients were stratified in categories of normoalbuminuria, microalbuminuria, and macroalbuminuria. Patients were followed for the outcomes ischemic stroke, myocardial infarction, and all-cause mortality until December 31, 2015. Five-year risk of outcomes were presented as cumulative incidence functions (with death as a competing event). Associations between albuminuria level and incidence of ischemic stroke, myocardial infarction, and all-cause mortality were evaluated with Cox proportional hazard regression adjusted for cardiovascular risk factors. Results The study population included 78,841 patients with type 2 diabetes (44.7% females, mean age 63.2). When comparing patients with microalbuminuria to patients with normoalbuminuria in an age- and sex-adjusted analysis, we found hazard ratios (HRs) of 1.45 (95% CI: 1.24–1.69), 1.45 (95% CI: 1.24–1.70), and 1.50 (95% CI: 1.39–1.61) for ischemic stroke, myocardial infarction, and all-cause mortality, respectively. Furthermore, macroalbuminuria was associated with HRs of 2.05 (95% CI: 1.70–2.48), 2.25 (95% CI: 1.86–2.71), and 2.03 (95% CI: 1.85–2.23) for ischemic stroke, myocardial infarction, and all-cause mortality, respectively. Similar results were found after adjusting for cardiovascular risk factors. Conclusions In this nationwide cohort study of patients with type 2 diabetes but without cardiovascular disease, patients with micro- and macroalbuminuria had a higher risk of incident ischemic stroke, myocardial infarction, and all-cause mortality. This finding supports that patients with micro- or macroalbuminuria should be screened regularly and followed closely in clinical practice. Moreover, these findings suggest that patients with type 2 diabetes and micro- or macroalbuminuria may benefit from intensive vascular risk reduction.

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