Ignored or underestimated - Evaluation and treatment of cardiovascular risk factors in patients with adrenal insufficiency Undertreatment of cardiovascular risk factors in patients with adrenal insufficiency

doi:10.21203/rs.3.rs-4857205/v1

Download PDF

Research Article

Ignored or underestimated - Evaluation and treatment of cardiovascular risk factors in patients with adrenal insufficiency Undertreatment of cardiovascular risk factors in patients with adrenal insufficiency

https://doi.org/10.21203/rs.3.rs-4857205/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Purpose

Patients with adrenal insufficiency (AI) are known to have a higher cardiovascular risk (CVR) than the normal population. In particular arteriosclerosis, coronary heart disease, arterial hypertension, hyperlipoproteinemia as well as metabolic disturbances contribute to the increased morbidity and mortality. Aim of this study was to evaluate known CVR factors along with the quality of care by the treating physicians.

Methods

To this end the medical records of AI patients were screened for CVR factors and the treatment initiated was documented. In addition, a questionnaire evaluating CVR factors was analyzed if available.

Results

In total, 327 AI patients were included in the study. At least 298 of these patients were found to have one or more CVR factors. Ninety-one patients were diagnosed with arterial hypertension, of these 40 patients (44%) still showed increased blood pressure (BP) values. Of all AI patients, about 25% (n = 83) did not have measurements to calculate their BMI, even though obesity is known as a major risk factor for cardiovascular events. Out of 46 patients with diabetes, one-quarter still had increased HbA1c values. Regarding hyperlipoproteinemia, only 4% of AI patients achieved normal lipid values across all parameters (n = 12). Interestingly, at least one lipid variable was untested in 150 patients (46%).

Conclusion

Our study demonstrates (1) the high rate of CVR factors in AI patients, leading to increased morbidity and eventually mortality, (2) AI patients are inadequately monitored and treated for CVR factors, (3) treating physicians should be aware of this risk to minimize complications where possible.

Adrenal insufficiency

cardiovascular risk

cardiovascular risk assessment

quality of healthcare

Adrenal insufficiency (AI) is a rare endocrine disorder affecting 100–126 individuals per million for primary adrenal insufficiency (PAI) [1] and about 400 individuals per million for secondary adrenal insufficiency (SAI) [2]. The pathophysiological mechanism is the inability of the adrenal glands to achieve adequate hormonal production due to adrenal disease (PAI) or due to malfunction of the pituitary gland (SAI). Tertiary adrenal insufficiency (TIA) comprises the suppression of the hypothalamic-pituitary-adrenal axis by exogenous glucocorticoid therapy. All types of AI lead to a lack of endogenous glucocorticoids (GC) that must be substituted to prevent patients from harmful symptoms or even death. Therefore, lifelong glucocorticoid replacement is essential in the treatment of PAI and SAI. The most frequently used GC formula for replacement therapy is hydrocortisone (HC), which has also been modified in the last years [3, 4]. Conventional glucocorticoid replacement therapy aims to mimic the physiological circadian rhythm of cortisol secretion as closely as possible to avoid side effects due to phases of hypo- and hypercortisolism. Usually, the administration of hydrocortisone (15–25 mg/d), is divided into two or three single doses [5, 6]. However, this substitution regimen leads to unphysiological plasma cortisol levels. These imbalances may foster a higher prevalence of coronary heart disease, and major adverse coronary events, and lead to increased mortality. While increased levels of GC are associated with obesity, high blood pressure, and hyperglycemia, decreased blood levels of cortisol result in a compensatory secretion of inflammatory mediators such as Interleukin-1 (IL-1), Interleukin-6 (IL-6) and tumor necrosis factor (TNF) [7, 8].

Patients with AI are known to have a higher CVR than the normal population [7, 9]. In particular, arteriosclerosis, coronary heart disease, arterial hypertension, hyperlipoproteinemia as well as metabolic disturbances contribute to increased morbidity and mortality [9–13]. Hydrocortisone doses above 20 mg per day seem to be associated with increased CVR due to the higher prevalence of common metabolic risk factors [6]. Thus, GC therapy may play a pivotal role in some of the well-known risk factors for cardiovascular disease (CVD). A similar observation was done in a population-based case-control study with 50,656 patients having received at least one prescription for systemic or non-systemic GCs [14] who showed an increased risk for cardiovascular and cerebrovascular events when compared to matched controls without GC intake with an adjusted odds ratio of 1.25 (95% confidence interval (CI) 1.21 to 1.29) [14]. Likewise, an increased cerebrovascular risk was found in GC-treated patients with SAI [15].

Aim of the study was to evaluate known CVR factors in AI patients as well as the quality of care by the treating physicians.

In this retrospective study, we screened the medical records of AI patients in three different endocrine outpatient practices (Bremen, Hamburg, and Leer) for CVR factors and documented the treatment initiated. If available, a questionnaire evaluating CVR factors was additionally analyzed. The questionnaire asked for existing diseases associated with increased CVR and family history concerning these diseases, as well as data for adjustable risk factors, such as BP or weight and height. Statistical analysis was performed by IBM SPSS Statistics, Version: 29.0.0.0 (241). We completed an ANOVA Analysis to compare the three participating outpatient practices in terms of the availability of data. A p-value less than 0.05 was considered significant.

Patients with TAI or with an unknown cause were excluded. Following inclusion criteria were applied: patients over 18 years of age, PAI or SAI, written informed consent for the questionnaire.

Blood parameters (lipids [total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and Lp(a)], uric acid, HbA1c) were analyzed using standardized measuring techniques. Lipid values were taken in a fasting state.

Blood pressure was either a self-measurement at home or measured in the doctor’s office. Values for weight and height were obtained in the same way.

Questionnaire see appendix.

In total, 363 AI patients were found, and 327 of these fulfilled the inclusion criteria. Two-hundred-ninety-eight of these patients were found to have one or more CVR factors. However, in 28 patients the risk factors were not sufficiently assessed, meaning they did not have any data for one or more risk factors. We found the following CVR factors: arterial hypertension, arteriosclerosis, coronary heart disease, peripheral artery disease, stroke, diabetes mellitus, hyperlipoproteinemia, hyperuricemia, obesity, sleep apnea syndrome, coagulation disorder, aneurysm, smoking, positive family history for the conditions mentioned above, as well as elevated values of lipids, uric acid, HbA1c, BMI or blood pressure. In total we identified 27 risk factors.

Risk factors

Only one patient did not have any risk factors. Most AI patients (n = 298) were found to have at least one risk factor (91%).

Between the three participating locations, there were significant differences regarding the evaluation of CVR factors.

On average, the patients in Hamburg were found to have about ten missing risk factors, whereas in Bremen about two factors were missing, and in Leer approximately three. There was a significant difference between Hamburg and Leer (p < 0.001) and Hamburg and Bremen (p < 0.001).

Arterial Hypertension

Elevated blood pressure (BP) was the leading global contributor to premature death in 2015 and is above all related to cardiovascular events such as stroke, myocardial infarction, heart failure, peripheral artery disease, and end-stage renal disease [16, 17]. Hypertension is defined as office systolic BP values > 140 mmHg and/or diastolic BP values > 90 mmHg [18].

In 91 patients (27.8%) arterial hypertension was documented with 44% (n = 40) of them still having a higher BP in one measurement. Almost half of the AI patients with known hypertension showed normal or low BP (n = 46) and five patients had no documented BP (5.5%) at all.

In patients, classified as not having arterial hypertension (n = 236), interestingly 21.6% showed elevated BP (n = 51). For 168 patients normal or low BP was documented (71.2%). Similar to patients with known arterial hypertension, a relevant proportion of this patient group (7.2%) did not provide any BP value (n = 17).

Concerning medication, three-quarters of the AI patients with known hypertension did not take any antihypertensive drugs according to the medical records. Furthermore, in patients who currently demonstrated high BP measurements, there were 65.9% who did not take any antihypertensive medication. Antihypertensive dose adjusting was performed by the treating family physicians in almost all cases.

Obesity

Overweight and obesity are defined as abnormal or excessive fat accumulation that may impair health. Obesity is a body mass index (BMI) greater than or equal to 30 [19]. Typical complications comprise type 2 diabetes, hypertension, fatty liver disease, and obstructive sleep apnea [20].

In total, 163 patients were overweight or obese. The threshold for obesity was reached by 78 of the AI patients with 13 having a BMI of 40 or higher.

About 80% of all AI patients with a documented diagnosis of obesity had an elevated BMI (n = 91), but only 60.3% were in fact obese. However, 17 of these cases (15.3%) had no documented BMI at all. Three of the patients with documented diagnosis of obesity had BMI values in the normal range (almost 3%).

Surprisingly, 5% of all AI patients who were not classified as suffering from obesity, were in fact obese (n = 11). Only 36.1% of this patient group had BMI values in the normal range (n = 78). The threshold for overweight was reached by 72 patients (33.3%). In 66 cases weight measurements were missing (30.6%). No weight measurements were documented for 66 patients (30.6%).

Patients with elevated BMI were often found to have more than one CVR factor. Merely five of these patients had elevated BMI as the only risk factor. Fifty-three of these patients were also known to have arterial hypertension (33%). Ninety-one patients with elevated BMI showed increased lipid levels (56%) as well.

Diabetes mellitus

The 48 mmol/mol (6.5%) HbA1c threshold was used to monitor blood glucose. Target HbA1c levels for patients with type 1 diabetes mellitus (T1DM) were between 6.5 and 7.5% [21]. The target levels for type 2 diabetes mellitus (T2DM) were recently defined individually between 6.5 and 8.5% [22]. For this study, we used the 7.5% threshold for both types. Typical complications of diabetes mellitus (DM) include cardiovascular, renal, peripheral vascular, ophthalmic, hepatic, or neurological diseases [23].

Although 46 patients suffered from DM, more than 1/4 (n = 12) still had increased HbA1c values.

No DM was documented for 281 patients. However, in 17.5% of these cases, an elevated HbA1c was found (n = 49). The majority had prediabetes, only in one case the threshold for DM was reached.

Only four of the diabetic patients took antidiabetics. There were eleven patients with known DM still having HbA1c over 7.5% who did not take any antidiabetic medication. Interestingly, there were also four patients without known DM and no data for HbA1c who did take antidiabetic drugs.

Hyperlipidemia

Hyperlipidemia is known to be an important CVR factor [24]. The most important subgroup is LDL cholesterol as it is the major risk factor in the formation of atherosclerotic plaques [24]. Triglycerides act as a predictive marker for cardiovascular events [25]. The role of Lp(a) has become more important over the last few years; it is considered to be an independent risk factor for CVD [26, 27].

Concerning hyperlipidemia, about 50% of all AI patients had at least one elevated lipid level (n = 165). Only three patients demonstrated lipids in the normal range in each subgroup (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and Lp(a)). Hundred-fifty of all AI patients were not adequately assessed, meaning that at least one value was unavailable. However, the existing lipid levels were normal. Out of the 165 patients with at least one elevated lipid, only 55 had documented hyperlipidemia. Eighteen patients with known hyperlipidemia had not been screened for elevated lipids (23.7%).

Only 17% of AI patients had data for Lipoprotein a (Lp(a)). Surprisingly no AI patient in Leer and only nine AI patients in Bremen had data for Lp(a).

In total, 126 patients had elevated total cholesterol levels (38.5%). There were six patients with data for total cholesterol but no further evaluation of the subgroups. In addition to elevated cholesterol levels, 53 AI patients also exhibited high values for LDL cholesterol.

Surprisingly, only 18 patients with known hyperlipidemia took lipid-lowering agents (23.7%). Moreover, in patients with at least one elevated lipid level, only 18.2% were taking lipid-lowering agents (n = 30).

Hyperuricemia

Hyperuricemia is closely related to CVD with higher levels of uric acid (UA) being a risk for CVD [28]. It is defined as an elevation of serum UA (> 6 mg/dL in women and > 7 mg/dL in men) [29]. We used the 5.7 mg/dL threshold as this was the laboratory reference. The underlying mechanisms of the increase in CVR are still not completely understood and are discussed controversially [30].

Only 21 of the AI patients were known to suffer from hyperuricemia (6%). Of these patients, five did not have data for uric acid (24%).

In 306 AI patients, no hyperuricemia was known. Though, 37 of these patients demonstrated elevated UA (12.1%). A big proportion (53.6%) did not have any measurements for UA (n = 164).

Unexpectedly, no patient with known hyperuricemia took uricostatic drugs but seven of the patients who, according to the documentation, did not know about their hyperuricemia.

Present data confirm the high prevalence of CVR factors in AI patients. Currently used GRT regimens fail to mimic the physiological rhythm of endogenous cortisol secretion leading to temporary hyper- and hypocortisolism [5]. The induction of classical metabolic risk factors for vascular disease by glucocorticoids (e.g. dyslipidemia, obesity) as well as the still unphysiological exposure under conventional glucocorticoid replacement therapy with subsequently increased IL-6 and the epinephrine deficiency itself may promote the increased CVR in AI [7].

Dual-release hydrocortisone preparations such as Plenadren® or Chronocort® have been introduced in recent years to mimic the circadian rhythm of cortisol more closely to prevent serious side effects [31].

Our study shows that there were patients with known adjustable CVR factors for whom the current status was not examined. In particular, endocrinologists need to have these CVR factors in mind or at least make sure the general practitioners focus on the correct adjustment of lipids, BP, blood glucose, and UA and try to reduce obesity in these patients.

Three different endocrine practices were included in this study. Although specialized in endocrinology a remarkable gap was found among them when analyzing the assessment of CVR factors. In contrast to Hamburg, the practices in Bremen and Leer additionally treated the patients in a general approach. This could explain the higher occurrence of not adequately assessed risk factors of patients in Hamburg.

Although we did not always have more than one BP measurement, it is obvious that even though patients had a high-risk profile they were not adequately monitored for BP (22 patients did not have any measurements). This also applies to weight measurements, where more than 25% (n = 83) did not have data for BMI as well as to blood glucose levels, where 76 patients did not have a value for HbA1c (23%).

In comparison to the normal population in Germany, AI patients in this study were more likely to be obese. We found a prevalence of about 1/3, whereas data from 2017 showed a prevalence of 16% obesity in Germany [32]. Obesity is closely related to DM and hyperlipidemia which further increases the CVR [33, 34]. For ¼ of the patients, no BMI was available which is a lot considering the importance of this factor according to the CVR [35, 36].

A lot of the diabetic patients were not taking any medication even though they still had elevated HbA1c levels. Almost ¼ (23.2%) did not have any data for HbA1c demonstrating that the treating physicians did not sufficiently check the adjustable risk factors.

There were differences in the availability of the subgroups of the lipids. Nevertheless, even the total cholesterol, which was the lipid that was measured in most of the patients, was not available for almost 100 patients (30%). As total cholesterol and LDL cholesterol are the most important lipids for CVR [24], it is obvious, that AI patients were treated inadequately. Only 55 of 165 patients with elevated lipids had documented hyperlipidemia, even though our data proved the diagnosis for the other 110 patients. Furthermore, it is well-known today that Lp(a) is an important CVR factor [37]. Only 54 patients (16.5%) were tested for this risk factor, showing insufficient assessment. This problem may partly be explained by the current unavailability of adequate medication to lower Lp(a) levels because statins do not lower them [26].

Serum UA levels were only evaluated in about 50% of the patients. Even in many patients with known hyperuricemia, no UA level was documented. It is interesting, that even though no hyperuricemia was documented, some patients still took uricostatic drugs. In our study, we found a prevalence of 15.3% with hyperuricemia (according to the serum UA) but in the general population, a prevalence of 21% was found [29]. This suggests that even more patients had hyperuricemia in the group without UA measurements (51.7%). Hypertension may be caused by mechanisms including the activation of the renin-angiotensin system, oxidative stress, endothelial inflammation, endothelin-1 activation, and nitrous oxide reduction [29]. Furthermore, it is linked to obesity mainly in a decreased excretion of UA by dysregulation of adipocytes [29].

Limitations of our study include the fact that we only had data from the endocrinological doctors’ offices. Although most affected patients were not adequately treated concerning CVR factors, it may be possible that the general practitioner controlled the CVR factors without drawing any consequences. Nevertheless, endocrinologists need to be aware of the increased CVR and should keep in mind to check whether existing CVR factors have been treated sufficiently.

In addition, checking blood pressure should comprise repeated measurements in a doctor’s office that yield values of 140/90 mmHg or higher [38]. In some cases, we did not have more than one measurement. Furthermore, it was not differentiated if the measurement was done in the doctor’s office or if it was a self-measurement at home.

Finally, as only 40 patients had all data for CVR factors (12.2%), it is conceivable that the endocrinologists did not adequately address the CVR for AI patients. Our data points out a missing awareness of their CVR profile.

We recommend developing a standardized procedure for patients with AI to minimize cardiovascular events and ensure the best possible treatment for these patients. A standardized questionnaire could be used to assess most of the important risk factors, including family history. Nevertheless, treating physicians should be advised to supervise the cardiovascular status regularly and help to reduce the modifiable risk factors. Firstly, regular monitoring of BP, lipid profile, glucose metabolism, and body composition should be integral components of patient care. Early detection of abnormalities allows for timely interventions to mitigate CVR [39]. Secondly, individualized glucocorticoid replacement regimens tailored to physiological requirements and circadian rhythms should be prioritized to minimize metabolic disturbances and optimize cardiovascular health [40, 41]. Thirdly, lifestyle modifications, including dietary adjustments, regular physical activity, smoking cessation, and stress management, should be emphasized to promote cardiovascular well-being [42–44]. Furthermore, judicious use of pharmacological agents, such as statins, antihypertensives, antidiabetic medications, and uricostatic drugs may be warranted to manage specific risk factors [45]. Importantly, interdisciplinary collaboration between endocrinologists, cardiologists, and primary care providers is essential to ensure holistic care delivery and optimal cardiovascular outcomes in this vulnerable population.

In conclusion, our study confirms the high prevalence of CVR factors in AI patients and reveals the serious lack of awareness regarding not only their disease [46, 47] but also their increased CVR profile and the urgent need for medical interventions in order to improve patients’ outcome.

Conflict of interest The authors have no relevant financial or non-financial interests to disclose.

Author contributions All authors contributed to the study's conception and design. Material preparation, data collection, and analysis were performed by Anja Wasmuth. The first draft of the manuscript was written by Anja Wasmuth and Birgit Harbeck; all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Ethical approval The study protocol was approved by the Ethics Committee of the University of Hamburg, Germany (WF-074/21).

Acknowledgment:

None

Meyer G, Badenhoop K, Linder R: Addison's disease with polyglandular autoimmunity carries a more than 2·5-fold risk for adrenal crises: German Health insurance data 2010–2013. Clin Endocrinol (Oxf).85(3):347 – 53.https://doi.org/10.1111/cen.13043. (2016)
Quinkler M, Beuschlein F, Hahner S, Meyer G, Schöfl C, Stalla GK: Nebennierenrinden-Insuffizienz – lebensbedrohliche Erkrankung mit vielfältigen Ursachen. Dtsch Arztebl International.110(51–52):882–8.https://doi.org/10.3238/arztebl.2013.0882. (2013)
Johannsson G, Lennernäs H, Marelli C, Rockich K, Skrtic S: Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study. Eur J Endocrinol.175(1):85–93.https://doi.org/10.1530/eje-15-1212. (2016)
Johannsson G, Nilsson AG, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, et al.: Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metab.97(2):473 – 81.https://doi.org/10.1210/jc.2011-1926. (2012)
Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al.: Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab.101(2):364 – 89.https://doi.org/10.1210/jc.2015-1710. (2016)
Filipsson H, Monson JP, Koltowska-Häggström M, Mattsson A, Johannsson G: The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients. J Clin Endocrinol Metab.91(10):3954–61.https://doi.org/10.1210/jc.2006-0524. (2006)
Rahvar A-H, Haas CS, Danneberg S, Harbeck B: Increased Cardiovascular Risk in Patients with Adrenal Insufficiency: A Short Review. BioMed Research International.2017:3691913.https://doi.org/10.1155/2017/3691913. (2017)
Vicenová B, Vopálenský V, Burýšek L, Pospíšek M: Emerging role of interleukin-1 in cardiovascular diseases. Physiol Res.58(4):481 – 98.https://doi.org/10.33549/physiolres.931673. (2009)
Debono M, Ross RJ, Newell-Price J: Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy. European Journal of Endocrinology.160(5):719 – 29.https://doi.org/10.1530/eje-08-0874. (2009)
Krzyzanowska K, Schnack C, Mittermayer F, Kopp HP, Hofer M, Kann T, et al.: High prevalence of abnormal circadian blood pressure regulation and impaired glucose tolerance in adults with hypopituitarism. Exp Clin Endocrinol Diabetes.113(8):430–4.https://doi.org/10.1055/s-2005-865772. (2005)
Erfurth EM, Hagmar L: Cerebrovascular disease in patients with pituitary tumors. Trends Endocrinol Metab.16(7):334–42.https://doi.org/10.1016/j.tem.2005.07.004. (2005)
Terzolo M, Pia A, Alì A, Osella G, Reimondo G, Bovio S, et al.: Adrenal incidentaloma: a new cause of the metabolic syndrome? J Clin Endocrinol Metab.87(3):998–1003.https://doi.org/10.1210/jcem.87.3.8277. (2002)
Chifu I, Quinkler M, Altieri B, Hannemann A, Völzke H, Lang K, et al.: Morbidity in Patients with Chronic Adrenal Insufficiency - Cardiovascular Risk Factors and Hospitalization Rate Compared to Population Based Controls. Horm Metab Res.56(1):20 – 9.https://doi.org/10.1055/a-2190-3735. (2024)
Souverein PC, Berard A, Van Staa TP, Cooper C, Egberts AC, Leufkens HG, et al.: Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case-control study. Heart.90(8):859 – 65.https://doi.org/10.1136/hrt.2003.020180. (2004)
Ngaosuwan K, Johnston DG, Godsland IF, Cox J, Majeed A, Quint JK, et al.: Cardiovascular Disease in Patients With Primary and Secondary Adrenal Insufficiency and the Role of Comorbidities. J Clin Endocrinol Metab.106(5):1284–93.https://doi.org/10.1210/clinem/dgab063. (2021)
Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, et al.: Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990–2015. Jama.317(2):165 – 82.https://doi.org/10.1001/jama.2016.19043. (2017)
Lewington S, Clarke R, Qizilbash N, Peto R, Collins R: Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet.360(9349):1903–13.https://doi.org/10.1016/s0140-6736(02)11911-8. (2002)
Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al.: 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J.39(33):3021 – 104.https://doi.org/10.1093/eurheartj/ehy339. (2018)
Zhang N, Wang G: From Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Populations: Decreased Bone Turnover Bioactivity. Diabetes Metab Syndr Obes.16:3657–67.https://doi.org/10.2147/dmso.S431194. (2023)
Perdomo CM, Cohen RV, Sumithran P, Clément K, Frühbeck G: Contemporary medical, device, and surgical therapies for obesity in adults. Lancet.401(10382):1116–30.https://doi.org/10.1016/s0140-6736(22)02403-5. (2023)
(DDG) DDGeV: S3-Leitlinie Therapie des Typ-1-Diabetes(2023); 5.1. (2023)
NVL-Programm von BÄK K, AWMF: S3-Leitlinie Nationale VersorgungsLeitlinie (NVL) Typ-2-Diabetes(2023). (2023)
Ali MK, Pearson-Stuttard J, Selvin E, Gregg EW: Interpreting global trends in type 2 diabetes complications and mortality. Diabetologia.65(1):3–13.https://doi.org/10.1007/s00125-021-05585-2. (2022)
Alloubani A, Nimer R, Samara R: Relationship between Hyperlipidemia, Cardiovascular Disease and Stroke: A Systematic Review. Curr Cardiol Rev.17(6):e051121189015.https://doi.org/10.2174/1573403x16999201210200342. (2021)
Stauffer ME, Weisenfluh L, Morrison A: Association between triglycerides and cardiovascular events in primary populations: a meta-regression analysis and synthesis of evidence. Vasc Health Risk Manag.9:671 – 80.https://doi.org/10.2147/vhrm.S52713. (2013)
Vinci P, Di Girolamo FG, Panizon E, Tosoni LM, Cerrato C, Pellicori F, et al.: Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives. Int J Environ Res Public Health.20(18).https://doi.org/10.3390/ijerph20186721. (2023)
Nurmohamed NS, Moriarty PM, Stroes ESG: Considerations for routinely testing for high Lp(a). Curr Opin Lipidol.33(3):213–8.https://doi.org/10.1097/mol.0000000000000828. (2022)
Zhang S, Wang Y, Cheng J, Huangfu N, Zhao R, Xu Z, et al.: Hyperuricemia and Cardiovascular Disease. Curr Pharm Des.25(6):700–9.https://doi.org/10.2174/1381612825666190408122557. (2019)
Saito Y, Tanaka A, Node K, Kobayashi Y: Uric acid and cardiovascular disease: A clinical review. J Cardiol.78(1):51 – 7.https://doi.org/10.1016/j.jjcc.2020.12.013. (2021)
Ekman B, Bachrach-Lindström M, Lindström T, Wahlberg J, Blomgren J, Arnqvist HJ: A randomized, double-blind, crossover study comparing two- and four-dose hydrocortisone regimen with regard to quality of life, cortisol and ACTH profiles in patients with primary adrenal insufficiency. Clin Endocrinol (Oxf).77(1):18–25.https://doi.org/10.1111/j.1365-2265.2012.04352.x. (2012)
Fink J, Seifert G, Blüher M, Fichtner-Feigl S, Marjanovic G: Obesity Surgery. Dtsch Arztebl Int.119(5):70–80.https://doi.org/10.3238/arztebl.m2021.0359. (2022)
Boutari C, DeMarsilis A, Mantzoros CS: Obesity and diabetes. Diabetes Res Clin Pract.202:110773.https://doi.org/10.1016/j.diabres.2023.110773. (2023)
Rössner S, Björvell H: Early and late effects of weight loss on lipoprotein metabolism in severe obesity. Atherosclerosis.64(2–3):125 – 30.https://doi.org/10.1016/0021-9150(87)90237-1. (1987)
Seravalle G, Grassi G: Obesity and hypertension. Pharmacol Res.122:1–7.https://doi.org/10.1016/j.phrs.2017.05.013. (2017)
Kim MS, Kim WJ, Khera AV, Kim JY, Yon DK, Lee SW, et al.: Association between adiposity and cardiovascular outcomes: an umbrella review and meta-analysis of observational and Mendelian randomization studies. Eur Heart J.42(34):3388 – 403.https://doi.org/10.1093/eurheartj/ehab454. (2021)
Fujino M, Nicholls SJ: Lipoprotein(a): cardiovascular risk and emerging therapies. Expert Rev Cardiovasc Ther.21(4):259 – 68.https://doi.org/10.1080/14779072.2023.2197593. (2023)
Jordan J, Kurschat C, Reuter H: Arterial Hypertension. Dtsch Arztebl Int.115(33–34):557–68.https://doi.org/10.3238/arztebl.2018.0557. (2018)
Teo KK, Rafiq T: Cardiovascular Risk Factors and Prevention: A Perspective From Developing Countries. Can J Cardiol.37(5):733 – 43.https://doi.org/10.1016/j.cjca.2021.02.009. (2021)
Kumar R, Wassif WS: Adrenal insufficiency. J Clin Pathol.75(7):435 – 42.https://doi.org/10.1136/jclinpath-2021-207895. (2022)
Guarnotta V, Amodei R, Giordano C: Metabolic comorbidities of adrenal insufficiency: Focus on steroid replacement therapy and chronopharmacology. Curr Opin Pharmacol.60:123 – 32.https://doi.org/10.1016/j.coph.2021.07.003. (2021)
van Oort S, Beulens JWJ, van Ballegooijen AJ, Burgess S, Larsson SC: Cardiovascular risk factors and lifestyle behaviours in relation to longevity: a Mendelian randomization study. J Intern Med.289(2):232 – 43.https://doi.org/10.1111/joim.13196. (2021)
Trautwein EA, McKay S: The Role of Specific Components of a Plant-Based Diet in Management of Dyslipidemia and the Impact on Cardiovascular Risk. Nutrients.12(9).https://doi.org/10.3390/nu12092671. (2020)
Marques-Vidal P: Comparison of lifestyle changes and pharmacological treatment on cardiovascular risk factors. Heart.106(11):852–62.https://doi.org/10.1136/heartjnl-2019-316252. (2020)
Saha SP, Banks MA, Whayne TF: Managing Cardiovascular Risk Factors without Medications: What is the Evidence? Cardiovasc Hematol Agents Med Chem.19(1):8–16.https://doi.org/10.2174/1871525718666200518093418. (2021)
Kampmeyer D, Lehnert H, Moenig H, Haas CS, Harbeck B: Experience pays off! Endocrine centres are essential in the care of patients with adrenal insufficiency. Eur J Intern Med.35:e27-e8.https://doi.org/10.1016/j.ejim.2016.07.008. (2016)
Kampmeyer D, Lehnert H, Moenig H, Haas CS, Harbeck B: A strong need for improving the education of physicians on glucocorticoid replacement treatment in adrenal insufficiency: An interdisciplinary and multicentre evaluation. Eur J Intern Med.33:e13-5.https://doi.org/10.1016/j.ejim.2016.04.006. (2016)

No competing interests reported.

Appendix.docx

Download PDF

Reviews received at journal
29 Sep, 2024
Reviewers agreed at journal
10 Sep, 2024
Reviewers invited by journal
27 Aug, 2024
Editor assigned by journal
06 Aug, 2024
Submission checks completed at journal
06 Aug, 2024
First submitted to journal
04 Aug, 2024

You are reading this latest preprint version

Ignored or underestimated - Evaluation and treatment of cardiovascular risk factors in patients with adrenal insufficiency Undertreatment of cardiovascular risk factors in patients with adrenal insufficiency

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction

Materials and Methods

Results

Discussion

Declarations

Acknowledgment:

References

Additional Declarations

Supplementary Files

Status:

Version 1