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Scientific Highlights: 2015 Latin American conference on cardiometabolic diseases management

Scientific Highlights: 2015 Latin American conference on cardiometabolic diseases management
  • Cardiometabolic
    Endocrinology and metabolism
  • Diabetes
    Hypertension
    Thyroid disorder

Resource type

Publication

Tags

Cardiometabolic diseases
Diabetes
Thyroid disorders
Hypertension
endocrine disorders
cardiovascular diseases
heart failure
heart rate control
cardiovascular autonomic neuropathy
resistant hypertension
Pre-diabetes
Type 2 diabetes
diabetic osteopathy
statins and diabetes
Diabetes in pregnancy
antidiabetic drugs
Thyroid dysfunction
treatment of thyroid nodules
subclinical hypothyroidism
hypothyroidism and pregnancy
hyperthyroidism and pregnancy
treatment adherence

Clinical management of cardiovascular diseases, diabetes and thyroid disorders

General practitioners, cardiologists, endocrinologists, internists and all other healthcare professionals managing cardiometabolic diseases attended this live educational conference to discuss the most recent research advancements and the best approaches for clinical management in daily practice.

Cardiovascular diseases (CVDs), diabetes mellitus (DM) and thyroid disorders often coexist in the same patient and are the most common pathologies in daily clinical practice. In Central and South America 8.1% of the 25 million population have diabetes (especially type 2). [1] Management of DM is a considerable challenge due the complexity of its pathophysiology and the high healthcare costs associated with managing the disorder and complications. Thyroid disorders are prevalent in Latin America primarily a result of iodine deficiency combined with genetic factors and impact cardiometabolic health. The prevalence of patients with concomitant heart failure and metabolic disorders particularly DM and thyroid diseases is increasing. Patients with heart failure and concomitant endocrine disorders represent a unique pathophysiological population as distinct metabolic and neurohormonal abnormalities coexist in patients with endocrine diseases. Furthermore, patients with heart failure and concomitant DM have a worse prognosis with increased rates of CV mortality and post-discharge hospitalisation. Hypertension, heart failure, DM and thyroid disorders all share common pathophysiological mechanisms and clinical issues that are problematical in clinical practice

This report highlights important topics discussed at a recent two-day meeting on cardiometabolic diseases, the learning objectives of which were to:

  • Understand the pathophysiology linking heart failure, hypertension, DM and thyroid disorders
  • Use the correct diagnostic and therapeutic strategies to face difficult cases in clinical practice
  • Consciously apply the most recent guidelines to the management of DM and thyroid diseases
  • Manage the complexity of cardiometabolic patients

 

References

1. International Diabetes Federation Diabetes Atlas sixth edition, 2013. www.idf.org/diabetesatlas

Heart rate control and CV risk

Prof Enrico Agabiti Rosei (University of Brescia, Brescia, Italy) explained that higher heart rate is associated with increased all-cause mortality [1], CV mortality, insulin resistance, obesity and DM. The prognostic validity of resting heart rate is associated with total and/or CV mortality independent of other CV risk factors and clinical outcome benefit is associated with heart rate reduction.

Sudden death risk also increases progressively with resting heart rate in the general population (Figure 1). [2] In addition a review of 11 studies involving 184,157 patients showed that elevated heart rate has a role in the development of CV disease in hypertension. [3]

In a French cohort study of 19,386 men and women with an 18-year follow-up both total and CV mortality were independently predicted by resting heart rate in both men and women. [4]

Resting heart rate also is a strong predictor of mortality in patients with hypertension and coronary artery disease in both western and Asian populations. [5]

Heart rate is a strong predictor of coronary vascular events and mortality and therapy that reduce it such as beta blockers or ivabradine are associated with reduced cardiac deaths in post myocardial infarction and chronic heart failure patients. However, beta-1 selectivity is important in patients with COPD and asthma, peripheral arterial disease, DM, dyslipidaemia and erectile dysfunction.

Prof Rosei stated that heart rate reduction is an effective tool to improve prognosis in patients with coronary arterial disease and chronic heart failure but this positive effect needs to be confirmed by appropriate randomised clinical trials for hypertension and other diseases.

[fig 1]

chart 1

References

  1. Kannel WB, et al. Am Heart J 1987;113:1489-94.
  2. Jouven X, et al. N Engl J Med 2005;352:1951-8.
  3. Palatini P. Hypertension 2011;58:745-50.
  4. Benetos A, et al. Hypertension 1999;33:44-52.
  5. Kolloch, et al. Eur Heart J 2008;29:1327-34.

 

Cardiovascular autonomic neuropathy in diabetes

Dr Maddaloni (University Campus Bio-Medico, Rome, Italy; Joslin Diabetes Center - Harvard Medical School- Boston, MA) emphasised that diabetic autonomic neuropathy is a widespread disorder of cholinergic, adrenergic and peptidergic autonomic fibres in diabetes being a deadly and often undiagnosed complication. [1]

Cardiovascular autonomic neuropathy (CAN) is an impairment of autonomic control of the CV system in diabetes. [2] Prevalence increases with age (up to 38% in type 1 DM [T1D] and up to 44% in type 2 DM [T2D]) and DM duration. [3-5]

CAN is life-threatening and clinical symptoms are non-specific and may not appear until long after diabetes onset.

CAN is associated with:

  • A high risk of CV arrhythmias and sudden cardiac death [6-7]
  • Presence of silent myocardial ischaemia and ischaemic stroke [8-9]
  • Intra- and perioperative CV instability [10]

Diagnosis of CAN relies on a number of CV autonomic tests including heart rate CV tests, heart rate variable time and frequency domain indices, orthostatic hypotension tests, QT interval and ambulatory blood pressure monitoring for dipping status. [5]

Cardiovascular autonomic reflex tests (CARTS) are considered the gold standard in autonomic testing. [5, 11] CARTs should be performed at T2D onset and 5 years after T1D (Figure 2).

[fig 2]

chart 2

In Vivo Corneal Confocal Microscopy (IVCCM) is an innovative test that allows rapid scanning of the cornea and is becoming a key tool in the early diagnosis of diabetic peripheral neuropathy. Recent evidence also suggests that it can have a role in the screening for autonomic neuropathies. [12]

Dr Maddaloni advised that in the management of CAN, drugs that reduce heart rate variability (HRV) should be avoided but long-term therapy with β-adrenergic blockers without ISA and ACEi that increase HRV are beneficial while SSRIs are preferred for the treatment of painful diabetic neuropathy. [13]

However α-lipoic acid is the only drug specifically tested for the treatment of CAN to show any benefits. [14]

References

  1. Deli G, et al. Neuroendocrinology 2013;98:267-80.
  2. Tesfaye S, et al. Diabetes Care 2010;33:2285-93.
  3. Low PA, et al. Diabetes Care 2004;27:2942-7.
  4. Pop-Busui R, et al. Circulation 2009;119:2886-93
  5. Spallone V, et al. Diabetes Metab Res Rev 2011;27:639-53.
  6. Gerritsen J, et al. Diabetes Care 2001;24:1793-8.
  7. Maser RE, et al. Diabetes Care 2003;26:1895-901.
  8. Young LH, et al. JAMA 2009;301:1547-55.
  9. Ko SH, et al. Diabet Med 2008;25:1171-7.
  10. Vinik AI, et al. Circulation 2007;115:387-97.
  11. Boulton AJ, et al. Diabetes Care 2005;28:956-62.
  12. Maddaloni E, et al. Diabetic Medicine 2015; 32:262-266.
  13. Aronson D. Diabetologia 1997;40:476-81.
  14. Ziegler D, et al. Diabetes Care 1997;20:369-73.

 

Pre-diabetes: relevance and treatment

Dr Napoli (University Campus Bio-Medico, Rome, Italy) reminded the delegates that DM prevalence is increasing in all regions of the world in both men and women [1] and in all age groups even in children and adolescents. [2]

Obesity prevalence has also increased [3] as well as consumption of total calories. Both have been shown to increase the risk of impaired glucose metabolism. [4]

Dietary intake is increasing while the cost of food has dropped (adjusted for inflation).

Patients at highest risk (prediabetes) must be identified. Prediabetes increases the risk for CV events and death. [5]

Prevention or delaying T2D

Studies conducted from a number of countries involving different ethnicities have shown that lifestyle intervention can prevent the development of T2D (Figure 3) and it is to date the most effective strategy for the prevention and treatment of T2D. [6]

[fig 3]

chart 3

Many pharmacological interventions have also been shown to be effective for the prevention of T2D (RR ranging from 0.28 to 0.80).

However, while lifestyle intervention has been demonstrated to be effective even after a follow-up of up to 20 years [7], in stark contrast, such a sustained effect has not been shown for drug therapy.

A number of strategies have been introduced to slow DM epidemic, such as taxing unhealthy food and drinks. This has been studied with respect to taxing junk food to reduce energy intake, weight and insulin levels. [8]

A study comparing peer mentoring, financial incentives and usual care for blood glucose control showed that peer mentoring improved glucose control in a cohort of African American veterans with diabetes more than the comparators. [9]

Dr Napoli emphasised that delaying or preventing T2D is cost-effective and may help to turn the tide of the diabetes epidemic.

References

  1. Danaei G, et al. Lancet 2011;378:31-40.
  2. Hsia ?, et al. Brit J Clin Pharmacol 2008;xx:xx. [cannot verify]
  3. WHO 2012
  4. Napoli N, et al. Diabetes Metab Res Rev 2010;26:10-12.
  5. DECODE study group. Lancet 1999;354:617-21.
  6. The DPP Research Group. NEJM 2002;346:393-403.
  7. Li G, et al. Lancet 2008;371:1783-9.
  8. Duffey KJ, et al. Arch Intern Med 2010;170:420-6.
  9. Long JA, et al. Annals Int Med 2012;156:416-24.

 

Diabetes and cardiovascular mortality

DM due to its associated hyperglycemia and hyperinsulinemia is a significant risk factor for CVD mortality, [1] with different patterns between T1D and T2D. [2] Dr Hillary Keenan (Joslin Diabetes Center - Harvard Medical School - Boston, MA, USA) said that rates of CVD have declined despite growth of other risk factors. [3]

In DM hyperglycemic toxicity affects the vasculature leading to potentially fatal pathology with oxidative stress and insulin resistance being potential mechanisms. Furthermore, inflammatory cytokines are increased.

In T2D, men experience the largest risk of CVD but women have the highest increase in death rates compared with the general population although the presence of renal disease overwhelms the gender effect. [4, 5]

In T1D gender differences for CVD risk occur as it is disproportionally increased in women compared with men. However, for both women and men with T1D there is an equally increased risk of CVD mortality. [2, 6-8]

A study demonstrated that early differences in CVD risk factors between male and females with T1D may contribute to the gender differences in terms of CV risk (Figure 4). [9]

[fig 4]

chart 4

Dyslipidemia is a key risk factor that is recognised in T2D but can be overlooked in T1D. The importance of specifically lowering low density lipids has been demonstrated in clinical trials with statins. [10]

A number of studies have shown that delivering insulin via a pump versus multiple daily injections gives a lower risk for both all-cause and CVD mortality which is improved further with continuous glucose monitoring or more frequent testing. [11-14]

Dr Keenan described potential strategies to predict or prevent CVD, including risk estimators for the general population and for T2D (Framingham Risk Score, United Kingdom Prospective Diabetes Score, respectively) and the various guidelines (American College of Cardiology, National Lipid Association). However, the application of such guidelines should probably be modified according to the type of DM.

References

  1. http://www.who.int/mediacentre/factsheets/fs310/en/;2.
  2. Livingstone SJ, et al. PLoS Medicine 2012;9:e1001321.
  3. O’Flaherty M, et al. Heart 2013;99:159-62.
  4. Madssen E, et al. J Scan Cardiovasc 2012;46:219-25.
  5. Nakhjavanu M, et al. Diab Vasc Dis Res 2015;12:150-1.
  6. Laing SP, et al. Diabetologia 2003;46:760-5.
  7. Maric C, et al. Am J Physiol Renal Physiology 2009;296:F680-8.
  8. Colhoun H, et al. J Am Coll Cardiol 2000;36:2160-7.
  9. Snell-Bergeon XX, et al. J Cardiovasc Trans Res 2012;5:446-62.
  10. De Ferranti SD, et al. Circulation 2014;130:1532-58.
  11. Steineck I, et al. BMJ 2015;350:h3234.
  12. Prober ?, et al. ADA abstract 2015. [cannot verify]
  13. Boulet ?, et al. ADA abstract 2015. [cannot verify]
  14. Cochrane Database Syst Review 2010.

Diabetic osteopathy

Bone fragility is an increasingly recognised complication of DM and is associated with decreased quality of life, increased costs, morbidity and mortality.

Dr Nicola Napoli (University Campus Bio-Medico, Rome, Italy) pointed out that many studies have demonstrated an association between both T1D and T2D and the risk of hip fracture. Bone mineral density is significantly reduced in subjects with T1D, while this is not true for people with T2D, despite the increase in the incidence of fragility fractures. This suggests a different pathophysiology leading to the increased bone fragility, with an impairment of bone quality more than a reduced mineralization in T2D [1]

Further insights have been gained from long-term studies with over 8 years follow-up. A higher risk of all non-vertebral fractures in men using insulin was seen [2], but DM was not associated with the risk of prevalent and incident vertebral fractures.

In T2D advanced glycation endproducts (AGEs) are increased as a result of non-enzymatic reactions between glucose and protein. The effects of AGEs include the formation of cross-links that increase the stiffness of bone collagen and the reduced resistance of bone. [3] Bone turnover is low in DM, as revealed by several serum markers such as serum type 1 procollagen N terminal, serum collagen type 1 cross-linked C-telopeptide, osteocalcin, bone-specific alkaline phosphatise, tartrate-resistant acid phosphatise 5b.. [4]

Latent autoimmune diabetes of adults (LADA) is a form of T1D with a similar phenotype to T2D (i.e. obesity and insulin resistance).

Dr Napoli emphasised that chronic hyperglycaemia as a result of either T1D or T2D gives rise to bone fragility (Figure 5).

chart 5

References

  1. Petit MA, et al. J Bone Miner Res 2010;25:285-9.
  2. Napoli N, et al. Diabetologia 2014;57:2057-65.
  3. Vashishth D, et al. J Mech Behav Biomed Mater 2011;4:1021-32.
  4. Rubin MR, et al J Bone Miner Res 2012;27:2231-7.

 

Thyroid nodules in clinical practice: from medical therapy to ultrasonically-guided intervention

Minimally invasive percutaneous interventions could be an option for treatment of benign thyroid nodules.

Prof Enrico Papini (Regina Apostolorum Hospital, Albano Laziale, Italy) described the natural history of benign thyroid nodules emphasising that approximately 15% increased by >50% after 5 years in an early study. [1] A more recent investigation showed that 11% of nodules exhibited 200% mean increase, constant growth and nodule growth was associated with a main nodule volume larger than 0.2mL after 5 years. [2]

Symptomatic benign thyroid nodules are problematic since a minority grow steadily and medical treatment is controversial while the standard therapy is surgery

However, although surgery is safe in high-volume centers, it is expensive, has a risk of complications and neck scarring and in most cases life-long substitution therapy is required. [3, 4]

Levothyroxine and iodine alone and in combination have been evaluated to treat thyroid nodules and overall the combination gave the best reduction. [5]

Currently thyroid stimulating hormone (TSH) suppression therapy is not routinely used as it is effective in only a minority of patients but can be considered in young patients with small goiters (no functional autonomy) from iodine-deficient areas. Non surgical techniques for thyroid tissue ablation are summarised in figure 6.

chart 6

Benign symptomatic solid nodules can be treated with laser ablation therapy (LAT) resulting in a mean volumetric decrease over 36 months. [6] Sonographically-guided radiofrequency ablation has also been used.

Prof Papini emphasised that treatment with percutaneous ethanol injection therapy (PEIT) or LAT effectively shrinks nodules, with minimal pain, performed at outpatient clinics and general anaesthesia is unnecessary with negligible cost. Both procedures have certain limits, in particular multiple procedures in large multiocular cysts are needed with PEIT and with LAT repeat treatment is required for large nodules and although complications are rare, they are potentially severe

References

  1. Papini E, et al. J Clin Endocrinol Metab 1998;83:780-3.
  2. Durante C, et al. JAMA 2015;313:926-35.
  3. Kandil E, et al. Surgery 2013;154:1346-52.
  4. Duclos A, et al. BMJ 2012;344:d8041.
  5. Grussendorf M, et al. J Clin Endocrinol Metab 2011;96:2786-95.
  6. Papini E, et al. J Clin Endocrinol Metab 2014;99:3653-9.

 

Debates on hot topics

Statins and diabetes: Pros

DM alone puts individuals in the high risk category for raised lipids, while those with DM plus ≥2 major atherosclerotic cardiovascular disease (ASCVD) event or evidence of end-organ damage are at very high risk (Figures 7, 8]. [1]

chart 8

Dr Hilary Keenan (Joslin Diabetes Center, - Harvard Medical School - Boston, MA, USA) reminded delegates that statins are the most effective drug therapy for reducing CVD risk in primary and secondary prevention having high efficacy and limited side effects (muscle pain/damage, insulin resistance, cognition, liver pathology).

Statins reduce the risk of CVD events in patients at high and low risk and have a cumulative risk reduction across all groups (odds ratio 0.86; 95% CI 0.79 to 0.94). [2-4]

Dr Keenan commented that their cost benefit analysis is favourable with 134 deaths avoided for 54 new DM cases and 86 vascular events/deaths avoided before an incidence DM case. [4]

References

  1. Bays HE, et al. J Clin Lipidology 2014;8:S1-36.
  2. Cholesterol Treatment Trialists’ Collaborators. Lancet 2012;380:581-90.
  3. Ridker PM, et al. J Am Col Card 2015;65:942-8.
  4. The Cochrane Collaboration 2014.

 

Statins and diabetes: Cons

Statin therapy reduces CV events and is used by a large proportion of people, so that even minor adverse effects and small risks can become substantial problems.

Results from clinical trials suggest a correlation between statin use and increased risk of developing DM, which is dose dependent, said Dr Ernesto Maddaloni. Statin therapy has been shown to be associated with decreased insulin sensitivity and secretion. [1]

In the JUPITER trial evaluating rosuvastatin in adults with no clinical or biochemical diagnosis of DM, both HbA1c (%) at 24 months and incident diabetes were increased versus placebo. [2] This finding was confirmed in a further meta-analysis of 13 major CV trials. [3]

Studies of people with familial hypercholesterolemia suggest that increased cellular uptake of cholesterol could be implicated in the increased risk of DM associated with statin therapy. [4]

When patients receiving intensive- or moderate-dose statin therapy were compared in 5 large clinical trials, an additional 2 cases of DM per 1000 patient years occurred in the intensive-dose groups. [5]

Dr Maddaloni reviewed other effective drugs such as ezetimibe, alirocumab or evolocumab that could be used instead of high-dose statins.

Preclinical data suggest that ezetimibe may improve glucose tolerance, possibly via an incretin-mediated mechanism.

A study evaluating ezetimibe plus simvastatin, versus atorvastatin or rosuvastatin monotherapy in UK general practice showed that more patients achieved LDL-C <2 mmol/L (77 mg/dl) in the combination group (Figure 10). [6]

[fig 10]

chart 10

This finding has been confirmed in other studies including the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) in which the combination of ezetimibe and simvastatin (versus simvastatin alone) was evaluated in 18,144 high-risk patients presenting with acute coronary syndrome. [7] The rate of CV death, MI, documented unstable angina requiring rehospitalisation, coronary revascularisation or stroke was reduced in patients treated with the combination.

References

  1. Cederberg H, et al. Diabetologia 2015;58:1109-17.
  2. Ridker PM, et al. NEJM 2008;359:2195-207.
  3. Sattar N, et al. Lancet 2010;375:735-42.
  4. Besseling J, et al. JAMA 2015;313:1029-36.
  5. Preiss D, et al. JAMA 2011;305:2556-64.
  6. McCormack T, et al. Int J Clin Pract 2010;64:1052-61.
  7. Cannon CP, et al. NEJM 2015;372:2387-97.

 

Poly-pharmacotherapy: Compliance and adherence

Dr Natalia De la Garza (Universidad Autónoma de Nuevo León, Hospital San José, Monterrey, Nuevo León, Mexico) explained that in order to improve adherence it is important to listen to the patient and customise the treatment regimen according to the patient’s wishes. Also help from family members, friends and community services should be obtained.

Adherence to medication decreases and the frequency of dosing increases (Figure 9). [1]

[fig 9]

chart 9

However, there is no consensus on what constitutes adequate adherence (80-95% in clinical trials) and physicians generally do not recognise poor adherence. 33-69% of all medication-related hospital admissions are due to poor adherence and the estimated cost is $1000 billion a year.

When a patient’s disease does not respond to treatment, poor adherence should be considered. It has been demonstrated that adherence trajectories predict future clinical endpoints in patients treated with statins. [2]

Numerous methods are available to measure adherence including direct (e.g. observing therapy, measurement of drug, metabolite or marker in blood) and indirect (including pill counts, assessment of clinical response, measurement of physiologic markers). [1] Each has advantages and disadvantages. [1]

In addition, indicators of poor adherence have been identified such as psychological problems, side effects, complexity of treatment, poor physician/patient relationship. [1, 3, 4]

Barriers to adherence occur with respect to the patient, therapy provider and the healthcare system and often result from poor knowledge or understanding and cost. [1]

The INTERACT trial evaluate the use of text messaging on adherence to CV preventative treatment and showed an improvement in adherence and 13% of patients who stopped their medication, resumed treatment. [5]

Strategies have been developed to improve adherence: [1]

  • Identify poor adherence
  • Emphasise the value of the treatment regimen and the effect of adherence
  • Determine the patient’s feelings about their ability to follow the regimen and then develop an appropriate strategy to promote adherence and in accordance with their wishes
  • Reinforce desirable behaviour and positive results
  • Provide clear instructions and make the regimen as simple as possible
  • Encourage the use of a medication-taking system
  • When adherence appears to be unlikely, consider treatments that are easier to take such as long half lives, extended release and transdermal patches

 

References

  1. Osterberg L, et al. NEJM 2005;5:487-97.
  2. Franklin JM, et al. Pharmacoepidemiology and Drug Safety 2015; Apr 22;doi:10.1002/pds.3787. Epub ahead of print.
  3. Sandoval X, et al. Rev Med Chile 2014;142:1245-52.
  4. De Vries FM, et al. Curr Med Res Opin 2015;31:595-602.
  5. Wald DS, et al. PLoS ONE 2014;9(12).

 

Subclinical hypothyroidism – to treat or not to treat: Pros

Subclinical hypothyroidism should be treated if thyroid-stimulating hormone (TSH) is >10, there is increased CV risk or pre-existing CVD and autoimmune thyroiditis, said Dr Alejandro Sosa Caballero (Tlacotalpan, Cuauhtémoc Distrito Federal DF, Mexico City, Mexico). The incidence is estimated to be 4-10%

TSH level fluctuates (circadian) with a nadir in the early afternoon and zenith in the evening and also increases with advancing age. [1]

Subclinical hypothyroidism is the most prevalent form of hypothyroidism and has been related to maternal-foetal complications in pregnant women as well as to CV risk. [2]

Evidenced-based clinical guidelines on hypothyroidism have been developed by a Task Force on Hypothyroidism commissioned by the Latin American Thyroid Society. [2] For the general population, the normal range of TSH (0.45-4.5 mIU/L) is recommended but higher levels for the elderly. Routine screening is not recommended. Furthermore, routine thyroid ultrasound should only be considered in patients with negative thyroid antibodies in order to identify those with autoimmune thyroiditis. [2]

Routine treatment with levothyroxine is not recommended in patients with subclinical hypothyroidism (SH) and there is inconsistent evidence for levothyroxine replacement therapy. [2]

Dr Sosa Caballero summarised the issues to consider when deciding if SH should be treated (see Figure 11)

chart 11

References

  1. Boucai L, et al. Thyroid 2011;21:5-11.
  2. Brenta G, et al. Arg Bras Endocrinol Metab 2013;57:265-98.

 

Subclinical hypothyroidism – to treat or not to treat: Cons

It is important that TSH is measured twice within a 2-3 month interval before treating subclinical hypothyroidism.

Prof Gabriela Brenta (Cesar Milstein Hospital, Buenos Aires, Argentina) presented several cases to demonstrate that clinical findings of hypothyroidism are very unspecific. 

Thyroid function is related to the weight of the patient and thyroid values have been shown to normalise when weight disorder is corrected. [1] In addition, cholesterol values differ between morbid obese and lean patients with similar TSH values. [2]

Treatment is not recommended when TSG is below 10 mU/L. Routine treatment for elderly and very elderly (>65 years and >80 years respectively) with subclinical hypothyroidism at TSH levels <10mU/L is not recommended. [3]

Levothyroxine treatment has been shown to reduce fatal and non-fatal ischaemic heart disease over a 7.5 year follow up. [4]

The US Preventative Services Task Force produced an evidence review for screening and treatment of thyroid dysfunction: [5]

  • Treatment of subclinical hypothyroidism was associated with decreased risk of CVD events versus no treatment in one cohort study
  • Treatment was not associated with improved health-related quality of life, cognitive function, blood pressure or body mass index in any studies
  • Treatment gave potential beneficial effects on lipid levels versus no treatment but this was of uncertain clinical significance

Prof Brenta stressed that lack of definitive evidence for a benefit does not equate to evidence for lack of benefit.

References

  1. Reinehr T, et al. Hormone Res 2008;70:51-7.
  2. Rotondi M, et al. Endocrine 2014;45:92-7.
  3. Brenta G, et al. Arg Bras Endocrinol Metabol 2013;57:265-98.
  4. Razvi S, et al. Arch Intern Med 2012;172:811-7.
  5. Rugge B, et al. http://www.ncbi.nlm.nih.gov/pubmed

 

In brief

New perspectives on heart failure

In patients with chronic heart failure and a reduced ejection fraction optimum medical therapy includes angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers and mineralocorticoid receptor antagonists, plus a diuretic, explained Dr Fernando Stuardo Wyss Quintana (International Society of Cardiology, Guatemala City, Guatemala).

A study comparing LCZ 696 (dual ARB/NEP inhibitor) with Enalapril in patients with a reduced ejection fraction showed that LCZ696 significantly reduced the rates of death from CV and any causes and the rates of hospitalisation for worsening heart failure. [1]

There is an unmet need for new therapy options – drugs with new mechanism of action. Ularitide and eplerenone are promising novel therapies.

Furthermore, a number of new devices to treat heart failure have been introduced [2]

References

  1. McMurray JJ, et al. NEJM 2014;371:993-1004.
  2. Kuck KH, et al. Europace 2014;16:109-28.

Role of interventional therapy in resistance hypertension

Prof Antonio Coca (University of Barcelona, Barcelona, Spain) stated that most patients with resistance (or refractory) hypertension require more than 3 drugs, with the fourth having a mechanism of action partially or totally different from the existing three.

Management of resistant or difficult to control hypertension involves routine 24-hour ambulatory blood pressure monitoring (which excludes ‘white coat’ hypertension and can evaluate prognosis), evaluation of treatment compliance, exclusion of secondary causes and the treatment approach. [1, 2]

Spironolactone, hemodynamic treatment, baroreflex activation therapy [3] and catheter-based renal sympathetic denervation [4] have been shown to be effective treatments although some need additional clinical trials to confirm promising initial results.

References

  1. 2013 ESH/ESC Guidelines. J Hypertens 2013;31:1281-357.
  2. 2013 ESH/ESC Guidelines. Eur Heart J 2013;34:2159-219.
  3. Scheffers IJ. et al. J Am Coll Cardiol 2010;56:1254-8.
  4. Krum H, et al. Lancet 2009;373:1275-81.

 

The nature of T2D: relationships to arterial and cardiac function and heart failure

Randomised clinical trials of glycaemic treatments show no benefit on macro-vascular endpoints, thus should such expensive treatments be used so intensively argued Dr Kennedy Cruikshank (Kings College London, London, UK). An important issue is lifestyle and weight in DM patients.

One study on the effect of hypoglycaemic agents on vascular complications in patients with DM concluded that although the treatments achieved lower levels of blood glucose, there were only minor differences in the occurrence of fatal or non-fatal events. [1] In addition, the ADVANCE Collaborative Group study comparing intensive and standard treatment showed little difference in macrovascular events, non-fatal stroke or MI and CV death between the two regimens. [2]

These findings suggest that management of T2D is unlikely to benefit from the continuing over focus on glycaemia.

Arterial dysfunction is detectable (by the presence of general and perivascular fat) before T2D is diagnosed or very early in the disease. Dr Kennedy Cruikshank expressed the view that T2D may be a vascular issue arising from inflamed/hypotoxic fat both before and during hyperglycaemia.

A number of non-invasive, calibrated methods (such as pulse-wave velocity signals and magnetic resonance imaging of aortic flow and stiffness) for measuring small and larger vessels are available. [3]

References

  1. Klimt CR, et al. JAMA 1987;240:37-42.
  2. ADVANCE Collaborative Group, et al. NEJM 2008;358:2560-72.
  3. Ben-Shlomo Y, et al. JACC 2014;63:636-46.

Cardiometabolic implications of thyroid dysfunction 

The heart is exquisitely sensitive to the effects of thyroid hormone and the most characteristic clinical symptoms and signs of thyroid dysfunction affect the heart and CV system. CV risk or disease should be assessed when thyroid dysfunction is suspected or known.

In addition, thyroid function should be assessed when CVDs including atrial fibrillation or sinus bradycardia are evident. Furthermore, screening for subclinical thyroid dysfunction may be beneficial as it may be associated with cardiac disorders.

Considerable research has been undertaken to develop selective thyroid hormone analogues as potential therapies for heart failure, metabolic syndrome and hypercholesterolemia added Dr Mogher Khamaisi (Harvard Medical School, Joslin Diabetes Center, Boston, MA, USA).  

 

How to choose the right drug for diabetes management?

With the increasing number of molecules currently available for the treatment of DM, the number of possible combination therapies is exponentially increasing. This could cause difficulties in the choice of the right drug for the right patient stated Dr Héctor Eloy Tamez Pérez (Faculty of Medicine and Universitary Hospital, Monterrey, Nuevo León, Mexico).

Hypoglycaemic efficacy is not the only parameter that should considered when choosing the optimum anti-diabetic drug. Indeed, several other factors impact morbidity and mortality of diabetic patients, such as hypoglycaemia, weight gain, cancer risk, dementia and renal function. Some of these factors could be ameliorated or worsened by such drugs.

Current recommendations proposed by international societies (ADA/EASD, AACE) suggest tailoring HbA1c targets and identifying the most suitable molecule based on patient’s features. In particular age, body weight, disease duration, life expectancy, comorbidities and established vascular complications should drive the therapeutic choice.

Overall, there is universal agreement that lifestyle modifications and metformin (unless contraindicated) should be the initial choice for the treatment of T2D.

Diabetes in pregnancy

Women with T1D and T2D have increased risk of adverse pregnancy outcomes including miscarriage and perinatal death. [1-3] Furthermore social and lifestyle factors are associated with poor pregnancy outcome. [3]

Recommendation for preconception care of women with DM involves individualised dietary advice (plus exercise), those with a BMI >27 Kg/m2 should have advice on weight loss, folic acid (5 mg/day) to be taken up to 12 weeks gestation. [3] 

Angiotensin-converting enzyme inhibitors, angiotensin-II receptor agonists and statins should be discontinued before conception or as soon as pregnancy is confirmed

Oral blood glucose-lowering agents should be discontinued before pregnancy and insulin substituted however metformin can be used as an adjunct or alternative to insulin. [4]

Dr Alejandro Sosa Caballero emphasised that postnatal care includes lifestyle advice, performing a fasting plasma glucose test 6-13 weeks after birth to exclude DM. [3]

References

  1. Casson IF. BMJ 1997;315:275-8.
  2. Hawthorne G. BMJ 1997;315:279-81.
  3. NICE 2015.
  4. Briggs GG, et al. Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Neonatal Risk. 7th ed. Philadelphia: Lippincott, Williams and Wilkins; 2005.

 

Cardiometabolic implications of antidiabetic drugs

Dr Enrique Gómez (Faculty of Medicine National Autonomous University of Mexico, Mexico City, Mexico) stated that there is an approximately 15% CV relative risk reduction for each 1% decrease in HbA1c.

A glycemic control algorithm provides practical advice for management from lifestyle modification to combination therapy with drugs with different modes of action. (Figure 12)

[fig 12]

chart 12

In patients treated with metformin there was a 39% relative risk reduction in fatal and non-fatal myocardial infarction (in the UK Prospective Diabetes Study). [1]

Gliptins (GLP-1 receptor agonists) may have non-glycaemic benefits such as improvement in blood pressure, lipid profiles and body weight.

Of note, sodium-glucose linked transporter 2 (SGLT2) inhibitors significantly reduce blood pressure in patients with T2D. [4]

References

  1. UK Prospective Diabetes Study (UKPDS 34). Lancet 1998;352:854-65.
  2. Green JB, et al. NEJM 2015;373:323-42.
  3. Scirica BM, et al. NEJM 2013;369:1317-26.
  4. Baker WL, et al J Amer Soc Hyperten 2014;8:262-75.

 

Hypothyroidism and hyperthyroidism in pregnancy

Both hypothyroidism and hyperthyroidism during pregnancy have been clearly associated with adverse effects in the foetus/neonate.

Risk groups for hypothyroidism include women >30 years of age, previous cervical irradiation, use of drugs such as amiodarone and lithium that interfere with thyroid function, use of iodinated contrast media, presence of circulating TPO antibody, personal history of previous thyroidectomy or thyroid disease, family history of thyroid disease and goitre and signs/symptoms of hypothyroidism. [1]

Subclinical hypothyroidism results in a high risk of miscarriage, and premature delivery but no excess complications occur with adequate treatment. [2, 3]

Prof Gabriela Benta (Ceser Milstein Hospital, Buenos Aires, Argentina) advised that treatment (levothyroxine) should be initiated as soon as thyroid disease is diagnosed.

Treated mothers still exhibit twice as many complication but when untreated the risk is 9-fold higher. [4]

Trimester-adjusted TSH reference ranges should be used to define hypothyroidism in pregnancy.

References

  1. Brenta G, et al. Arq Bras Endocrinal Metab 2013;57:265-87.
  2. Abalovich M, et al. Thyroid 2002;12:63-8.
  3. Casey BM, et al. Obstet Gynecol 2005;105:239-45.
  4. Mestman JH, et al. Clin Obstet Gynecol 1997;40:45-64.

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Santa María Huatulco, Mexico
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General practitioners, Cardiologists, internists, Healthcare professionals
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by Excemed
Cardiometabolic, Endocrinology and metabolism