Risk factors for aortic stenosis

Vol. 18, N° 11 - 19 Feb 2020

Prof. Magnus Bäck , FESC

Assoc. Prof Susanna C. Larsson

Although aortic valve stenosis (AVS) shares several risk factors with atherosclerosis, lipid-lowering therapy does not reduce AVS progression. Elevated lipoprotein(a), hypertension, chronic kidney disease, and diabetes all increase the risk of AVS. In addition, recent studies have emphasised increased body mass index (BMI) as a particularly strong AVS risk factor. Modifying risk factors for AVS may reduce morbidity and potentially avoid valve interventions with health economic benefits.

Topic(s):

Valvular Heart Disease

Introduction

Aortic valve disease includes aortic valve stenosis (AVS), aortic regurgitation (AR) and a combination of the two. The increased prevalence of non-rheumatic aortic valve disease parallels an increasingly ageing population. Degenerative AVS is the most common valvular heart disease and develops from fibrocalcific changes of the aortic valve cusps, resulting in reduced valve opening and eventually haemodynamic obstruction of the left ventricular outflow. Although a reported slight decline in AVS incidence suggested that improved cardiovascular risk factor control may limit the development of AVS in the Western world, cardiovascular prevention by means of lipid-lowering therapy has been shown to be inefficacious in reducing AVS progression. In addition to dyslipidaemia, other traditional cardiometabolic risk factors such as obesity [1-4], hypertension [3-6], and diabetes [3, 4, 6, 7], have also been shown to increase the risk of AVS in retrospective studies. Despite this shared risk factor profile and the common co-existence of atherosclerosis and valvular calcification, a substantial proportion of patients with AVS do not have concomitant coronary artery disease. Assessing the association of traditional cardiovascular risk factors with incident aortic valve disease is therefore important in order to identify potential preventive strategies in valvular heart disease. Identifying key risk factors for AVS may, in addition, provide clues for risk stratification and future interventional trials to slow down AVS progression and to avoid, or at least postpone, aortic valve interventions.

Aortic Stenosis Interventions

Over time, the number of aortic valve interventions has increased both in Europe (Figure 1A) and the USA (Figure 1B), with a decreasing proportion of surgical aortic valve replacement (SAVR) in favour of transcatheter aortic valve implantation/replacement (TAVI/TAVR) (Figure 1C, Figure 1D). Although TAVI increased earlier in European than in American populations, the proportion of surgical to transcatheter aortic valve interventions now approaches 60:40 on both sides of the Atlantic (Figure 1C, Figure 1D) [8]. The striking sex differences in Figure 1A and Figure 1B in terms of the interventional management of AVS (at least in part) also illustrates the higher AVS incidence in males compared with females [1-4]. The inflation-adjusted annual expenditure of AVS interventions in the USA doubled between 2003 and 2016 [8]. In addition to avoiding periprocedural and postprocedural risks for AVS patients, the prevention of AVS incidence would hence also be anticipated to have substantial health economic benefits.

Figure 1.  Aortic Valve Interventions Over Time in Sweden (left panels) and the USA (right panels). The upper panels show the number of aortic valve interventions in males (blue) and females (orange) per 100,000 individuals between 2003 and 2016/18. The lower panel show the proportion of surgical aortic valve replacement (SAVR; orange) and transcatheter aortic valve implantation/replacement (TAVI/TAVR; blue), respectively.

Panels A and B represent data from the Swedish National Board of Health and Welfare (Socialstyrelsen), accessed on 23/11/2019 at http://www.socialstyrelsen.se. Panels B and D from Alkhouli M, et al. Eur Heart J. 2019 [8] are reprinted by permission of Oxford University Press on behalf of the European Society of Cardiology.

Lipids and Lipoproteins in Relation to AVS Risk

Observational studies have established an association of increased levels of low-density lipoprotein (LDL) cholesterol with AVS. Likewise, a recent Mendelian randomisation study showed a positive association between genetically predicted LDL cholesterol levels and AVS [9]. However, large clinical trials revealed a lack of effect of statin treatment to decrease the haemodynamic progression of AVS. Whether these conflicting results represent pleiotropic effects of statins of which some may be detrimental for AVS or the lack of a causal effect of LDL cholesterol on AVS remains unclear. Other lipoproteins have attracted an increasing interest for their possible causal involvement in AVS. Lp(a) is an atherogenic lipoprotein that was identified as being genome-wide significantly associated with aortic valve calcification and AVS [10]. Mechanistic studies have also generated support to the importance of Lp(a) and Lp(a)-associated oxidised phospholipids in AVS pathophysiology [11]. Furthermore, increased Lp(a) levels in patients with AVS is an indicator of faster haemodynamic progression [12] as well as increased valve calcification activity as determined using the radiotracer [13] F-NaF for PET imaging [14]. Mendelian randomisation studies have associated elevated Lp(a) levels and corresponding genotypes with increased risk of AVS in the general population, with a 10% to 30% increase in the risk of AVS per 10 mg/dL increment of genetically predicted Lp(a) levels [15]. Compared with other cardiovascular outcomes, Lp(a) lowering could potentially prevent 1 in 7 cases of AVS compared with 1 in 14 cases of myocardial infarction [16]. Importantly, statins may not alter Lp(a) levels, which should be taken into account when considering the lack of beneficial effects obtained by LDL-lowering in AVS. Although it remains to be established whether these observations translate into a therapeutic value of Lp(a) lowering for slowing down AVS progression, Lp(a) could potentially also be considered as a biomarker to guide clinical follow-up, timing of intervention, and risk stratification in AVS patients.

Obesity

We recently reported that that body mass index (BMI) is associated with the risk of developing AVS (Figure 2). In brief, our analysis involved 71,817 men and women who were free of cardiovascular disease and followed for a mean of 15.3 years. AVS cases were ascertained through linkage with nationwide registers on hospitalisation and causes of death. Overweight and obese subjects had a hazard ratio (HR) of 1.24 (1.05–1.48) and 1.81 (1.47–2.23), respectively, for incident AVS. The highest risk of AVS was present in obese individuals with substantially increased waist circumference (WC), suggesting that the increased risk of AVS associated with overall obesity may be enhanced by an abdominal body fat distribution (Figure 2). Furthermore, the associations of BMI and WC with AVS persisted when the analysis was restricted to participants without a history of diabetes, hypertension, and hypercholesterolaemia, suggesting that isolated obesity is also a risk factor, even in the absence of a metabolic syndrome. A Mendelian randomisation study subsequently established the causal relation of BMI with incident AVS [2]. In 367,703 UK Biobank participants [2], each 1 kg/m2 increase in genetically predicted BMI increased the risk of AVS by 13% (1.05–1.21), with an even stronger association for fat mass index (OR=1.46; 1.13–1.88) [2]. Interestingly, AVS exhibited the strongest association with BMI and fat mass index among the 14 examined cardiovascular disease outcomes, further reinforcing the strong connection between obesity and the risk of developing AVS, as depicted in Figure 2. We have estimated that up to 10% of AVS cases could be prevented if the entire population maintained a BMI of 25 kg/m2 or less [1].

Figure 2. Obesity Increases the Risk of Incident Aortic Stenosis. The association of body mass index (BMI), abdominal adiposity (waist circumference), and fat mass index with an increased risk of incident aortic valve stenosis. Modified from Larsson SC, et al. Eur Heart J. 2017 [1] and Larsson SC, et al. Eur Heart J. 2019 [2] by permission of Oxford University Press on behalf of the European Society of Cardiology.

 

Hypertension: Putting Pressure on the Aortic Valve

Hypertension is present in 21% of those with AVS, and 1.1% of hypertensive subjects have AVS [17]. However, only a few longitudinal studies have evaluated the association of hypertension with incident AVS [3, 5]. A recent cohort study of 5.4 million subjects followed for a median of 9.2 years through UK electronic healthcare records showed that elevated systolic blood pressure increased the risk of both AVS and AR with approximately 40% for each incremental 20 mmHg [5]. Diastolic and pulse pressures were also associated with an increased incidence of aortic valve disease [5]. It should also be considered that hypertension may affect the clinical presentation of AVS. Early detection and treatment of hypertension for the prevention of aortic valve disease therefore warrants further exploration in prospective, observational, and Mendelian randomisation studies.

Lifestyle Risk Factors

Since both obesity and hypertension are risk factors for AVS [1, 5, 6], additional benefit would be expected if physical activity leads to weight loss and reduced blood pressure. However, no significant association has hitherto been established between physical activity (assessed by questionnaire) and AVS risk [3, 18]. This may suggest that the effect of physical activity on the cardiovascular risk factors are too modest to provide a significant reduction in AVS incidence. Along the same line, diet influences cardiometabolic risk factors but no associations of overall healthy dietary patterns or major food groups with the risk of AVS have been reported [13]. Taken together, the effects of physical activity and diet on potential intermediates, including BMI, diabetes, hypertension, and hypercholesterolaemia, may not be sufficient to alter the risk of AVS. This is, however, in contrast to other cardiovascular outcomes, with inverse associations of healthy dietary patterns and physical activity and risk of myocardial infarction, heart failure, and stroke. Hence, the existing data today suggest that, although lifestyle interventions on diet and physical activity may be less likely to directly affect AVS, it appears reasonable to encourage physical activity and a healthy diet for AVS patients given the potential beneficial effects on other cardiovascular outcomes.

Similar to observations for other cardiovascular diseases, light-to-moderate alcohol consumption appears to be protective for valve calcification [19] and incident AVS [20]. Likewise, observational studies have found that current smoking is associated with a 30% to almost twofold increased risk of AVS [3, 4, 20], and a higher risk with increasing smoking intensity. Importantly, smoking being a modifiable risk factor for AVS is underlined by the time-dependent decrease in AVS risk in former smokers depending on the time passed since smoking cessation. This approaches the risk observed for never smokers after 10 non-smoking years [20].

Renal Function

A database study of serum creatinine measures from 1.1 million subjects revealed that decreased glomerular filtration rate (GFR) was associated with an increased risk of incident AVS [21]. Compared with reference (GFR >90 ml/min/1.73 m2), even a slight decrease in kidney function (GFR 60-90) was associated with a 14% higher risk of developing AVS. This risk increased with decreasing kidney function reaching a 56% increased risk of incident AVS in subjects with a GFR <30. These results indicate that even relatively mild degrees of renal impairment increase the risk of developing AVS. Although the exact mechanistic link between chronic kidney disease and AVS remains unknown, changes in pro- and anti-calcifying factors and also effects on calcium/phosphate balance could be of importance and warrant further examination to establish possible measures for preventing AVS in chronic kidney disease.

Diabetes

Type 2 diabetes mellitus (T2DM) was associated with an increased incident AVS in retrospective studies [3, 4, 6, 7]. Given the close connection between cardiometabolic risk factors, it is also important that obesity is taken into consideration as a possible confounder for the relationship between T2DM and AVS [7]. In mechanistic terms, it is also important to note that type 1 diabetes mellitus (T1DM) and T2DM exhibit similar patterns for increasing AVS risk, although the number of AVS cases was too low to establish any significant associations with T1DM in the only available study addressing that question [7]. Recent clinical trials have put the spotlight on the beneficial effects of anti-diabetic treatments on cardiovascular outcomes also in non-diabetic subjects, which would warrant further examination in AVS.

Conclusions

Today, the increasing burden of AVS and the resulting increased AVS interventions represent a burning clinical and health economic issue. Importantly, although the risk factor profile for AVS resembles that of coronary heart disease, there is also evidence of differential effects measures for the individual risk factors addressed. For example, whereas LDL-lowering by statin treatment did not slow down AVS progression in clinical trials, Lp(a) appears to be more strongly associated with the risk of AVS than with the risk of myocardial infraction [16]. Likewise, AVS ranked first in the increased cardiovascular risk associated with obesity [2]. There is an urgent need for prospectively evaluating the effects of risk modifications as well as treatments targeting the potential AVS risk factors. Examples of such therapeutic strategies could potentially include weight loss, Lp(a) lowering, smoking cessation, as well as antihypertensive and antidiabetic treatments. Deciphering the risk factors contributing to AVS incidence and progression will be key in designing preventive measures for slowing down AVS progression, and eventually preventing, or at least postponing, AVS interventions.

References

1. Larsson SC, Wolk A, Hakansson N, Bäck M. Overall and abdominal obesity and incident aortic valve stenosis: two prospective cohort studies. Eur Heart J. 2017;38:2192-7. 
2. Larsson SC, Bäck M, Rees JMB, Mason AM, Burgess S. Body mass index and body composition in relation to 14 cardiovascular conditions in UK Biobank: a Mendelian randomization study. Eur Heart J. 2019 Jun 13. [Epub ahead of print]. 
3. Eveborn GW, Schirmer H, Lunde P, Heggelund G, Hansen JB, Rasmussen K. Assessment of risk factors for developing incident aortic stenosis: the Tromso Study. Eur J Epidemiol. 2014;29:567-75. 
4. Martinsson A, Ostling G, Persson M, Sundquist K, Andersson C, Melander O, Engstrom G, Hedblad B, Smith JG. Carotid plaque, intima-media thickness, and incident aortic stenosis: a prospective cohort study. Arterioscler Thromb Vasc Biol. 2014;34:2343-8. 
5. Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, Kitzman DW, Otto CM. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol. 1997;29:630-4. 
6. Yan AT, Koh M, Chan KK, Guo H, Alter DA, Austin PC, Tu JV, Wijeysundera HC, Ko DT. Association Between Cardiovascular Risk Factors and Aortic Stenosis: The CANHEART Aortic Stenosis Study. J Am Coll Cardiol. 2017;69:1523-32. 
7. Larsson SC, Wallin A, Hakansson N, Stackelberg O, Bäck M, Wolk A. Type 1 and type 2 diabetes mellitus and incidence of seven cardiovascular diseases. Int J Cardiol. 2018;262:66-70. 
8. Alkhouli M, Alqahtani F, Ziada KM, Aljohani S, Holmes DR, Mathew V. Contemporary trends in the management of aortic stenosis in the USA. Eur Heart J. 2019 Aug 13. [Epub ahead of print]. 
9. Allara E, Morani G, Carter P, Gkatzionis A, Zuber V, Foley CN, Rees JM, Mason AM, Bell S, Gill D, Lindstroem S, Butterworth AS, Di Angelantonio E, Peters J, Burgess S. Genetic Determinants of Lipids and Cardiovascular Disease Outcomes: A Wide-angled Mendelian Randomization Investigation. Circ Genom Precis Med. 2019 Nov 22. [Epub ahead of print]. 
10. Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso GM, Kerr KF, Pechlivanis S, Budoff MJ, Harris TB, Malhotra R, O'Brien KD, Kamstrup PR, Nordestgaard BG, Tybjaerg-Hansen A, Allison MA, Aspelund T, Criqui MH, Heckbert SR, Hwang SJ, Liu Y, Sjogren M, van der Pals J, Kalsch H, Muhleisen TW, Nothen MM, Cupples LA, Caslake M, Di Angelantonio E, Danesh J, Rotter JI, Sigurdsson S, Wong Q, Erbel R, Kathiresan S, Melander O, Gudnason V, O'Donnell CJ, Post WS ; CHARGE Extracoronary Calcium Working Group. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368:503-12. 
11. Mathieu P, Arsenault BJ, Boulanger MC, Bosse Y, Koschinsky ML. Pathobiology of Lp(a) in calcific aortic valve disease. Expert Rev Cardiovasc Ther. 2017;15:797-807. 
12. Capoulade R, Chan KL, Mathieu P, Bosse Y, Dumesnil JG, Tam JW, Teo KK, Yang X, Witztum JL, Arsenault BJ, Despres JP, Pibarot P, Tsimikas S. Autoantibodies and immune complexes to oxidation-specific epitopes and progression of aortic stenosis: Results from the ASTRONOMER trial. Atherosclerosis. 2017;260:1-7. 
13. Larsson SC, Wolk A, Bäck M. Dietary patterns, food groups, and incidence of aortic valve stenosis: A prospective cohort study. Int J Cardiol. 2019;283:184-8. 
14. Zheng KH, Tsimikas S, Pawade T, Kroon J, Jenkins WSA, Doris MK, White AC, Timmers N, Hjortnaes J, Rogers MA, Aikawa E, Arsenault BJ, Witztum JL, Newby DE, Koschinsky ML, Fayad ZA, Stroes ESG, Boekholdt SM, Dweck MR. Lipoprotein(a) and Oxidized Phospholipids Promote Valve Calcification in Patients With Aortic Stenosis. J Am Coll Cardiol. 2019;73:2150-62. 
15. Cairns BJ, Coffey S, Travis RC, Prendergast B, Green J, Engert JC, Lathrop M, Thanassoulis G, Clarke R. A Replicated, Genome-Wide Significant Association of Aortic Stenosis With a Genetic Variant for Lipoprotein(a): Meta-Analysis of Published and Novel Data. Circulation. 2017;135:1181-3. 
16. Afshar M, Kamstrup PR, Williams K, Sniderman AD, Nordestgaard BG, Thanassoulis G. Estimating the Population Impact of Lp(a) Lowering on the Incidence of Myocardial Infarction and Aortic Stenosis-Brief Report. Arterioscler Thromb Vasc Biol. 2016;36:2421-3. 
17. Pate GE. Association between aortic stenosis and hypertension. J Heart Valve Dis. 2002;11:612-4. 
18. Sarajlic P, Wolk A, Bäck M, Larsson SC. Physical Activity Does Not Reduce Aortic Valve Stenosis Incidence. Circ J.  2018;82:2372-4. 
19. Markus MR, Lieb W, Stritzke J, Siewert U, Troitzsch P, Koch M, Dorr M, Felix SB, Volzke H, Schunkert H, Baumeister SE. Light to Moderate Alcohol Consumption Is Associated With Lower Risk of Aortic Valve Sclerosis: The Study of Health in Pomerania (SHIP). Arterioscler Thromb Vasc Biol. 2015;35:1265-70. 
20. Larsson SC, Wolk A, Bäck M. Alcohol consumption, cigarette smoking and incidence of aortic valve stenosis. J Intern Med. 2017;282:332-9.
21. Vavilis G, Bäck M, Occhino G, Trevisan M, Bellocco R, Evans M, Lindholm B, Szummer K, Carrero JJ. Kidney Dysfunction and the Risk of Developing Aortic Stenosis. J Am Coll Cardiol. 2019;73:305-14. 

Notes to editor

Authors:

Magnus Bäck1,2, MD, PhD, FESC; Professor of Cardiology

Susanna C. Larsson3,4, PhD; Associate Professor of Epidemiology

1. Karolinska University Hospital, Division of Valvular and Coronary Diseases, Stockholm, Sweden;
2. Karolinska Institutet, Translational Cardiology, Department of Medicine, Stockholm, Sweden;
3. Karolinska Institutet, Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Stockholm, Sweden;
4. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

Categories: iatrika

Valvular heart disease

Valvular heart disease: improved procedural success and prediction of outcomes 

Thomas F Lüscher, MD, FESC

European Heart Journal, Volume 41, Issue 8, 21 February 2020, Pages 899–902, https://doi.org/10.1093/eurheartj/ehaa111

Published:

 

21 February 2020

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts.

Aortic valve disease increases in prevalence and incidence with age, particularly after age 60. As the biology of this disease is still poorly understood,1 the only current treatment is valve replacement. Until recently, this was the field for surgeons; however, with the development of transarterial valve implantation or TAVI, interventional cardiologists expanded their therapeutic spectrum substantially, initially in high-risk2 and more recently even in low-risk patients.3 This Focus Issue on valvular heart disease starts with the ‘The year in cardiology: valvular heart disease’ by Bernard Prendergast from the John Radcliffe Hospital in Oxford, UK, and colleagues.4 They remind us that after decades as a Cinderella discipline, valvular heart disease now occupies the centre stage of cardiovascular medicine. Changing societal demographics and an ageing population (with increasing prevalence of degenerative disease), advances in imaging, and the explosion of interest in TAVI (supported by a series of landmark clinical trials) have attracted clinicians, researchers, engineers, device manufacturers, and investors, and transformed the landscape of clinical management. Indeed, a recent meta-analysis concluded that compared with surgical valve replacement, TAVI is associated with a reduction in all-cause mortality and stroke up to 2 years irrespective of baseline surgical risk and type of system used.5 However, the incidence of stroke and pacemaker implantation was lower in those undergoing TAVI with balloon-expandable compared with self-expandable valves. In contrast, patients treated with new-generation balloon-expandable valves more often suffered from major or life-threatening bleedings than those with new-generation self-expandable valves, while mortality at 30 days was not different. Thus, 2019 has been a ‘leap’ year for valvular heart disease, and TAVI procedures will further increase.6

Based on these recent developments, TAVI has become the preferred procedure in patients with aortic stenosis in many countries. This is further analysed in the article entitled ‘Contemporary trends in the management of aortic stenosis in the USA’ by Mohamad Alkhouli and colleagues from the Mayo Clinic College of Medicine and Science in Rochester, Minnesota, USA (Figure 1).7 They utilized the National-Inpatient-Sample to assess temporal trends in the incidence, cost, and outcomes of aortic stenosis interventions between 2003 and 2016. During that period, aortic stenosis interventions increased from 96 to 137 per 100 000 individuals over 60 years of age. In-hospital expenditure almost doubled from US$2.28 billion in 2003 to US$4.33 in 2016. Among patients who underwent aortic valve replacement, the proportion of TAVI increased from 11.9% in 2012 to 43.2% in 2016. Males and Hispanics had lower proportions of TAVI compared with females and White patients. Adjusted in-hospital mortality of isolated surgery decreased from 5.4% in 2003 to 3.3% in 2016, while it decreased from 4.7% in 2012 to 2.2% in 2016 for TAVI. The incidence of new dialysis, permanent pacemaker implantation, and blood transfusion decreased after both TAVI and surgery between 2012 and 2016. However, the rate of post-operative stroke did not decrease significantly. Length of stay and cost of hospitalization decreased after both surgery and TAVI, although the latter remained higher with TAVI. Rates of non-home discharge decreased over time after TAVI but remained stable after isolated surgery. Thus, this nationwide survey documents the increasing incidence of interventions for aortic stenosis, the rising cost of care, and the paradigm shift in aortic valve replacement practice in the USA. The manuscript is accompanied by a balanced Editorial by Catherine M. Otto from the University of Washington in Seattle, Washington, USA.8

Figure 1

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Temporal changes in the proportion of transcatheter aortic valve implantation for aortic stenosis. (A) Annual change in the proportions of TAVI among all aortic stenosis patients >60 undergoing aortic valve replacement. (B) Proportion of TAVI to all aortic valve replacement in different age groups. (C) Proportion of TAVI to all aortic valve replacement in males and females. (D) Proportion of TAVI to all aortic valve replacement in different racial groups. AS, aortic stenosis; TAVI, transcatheter aortic valve replacement. *P-values were <0.001 for all trend lines (from Alkhouli M, Alqahtani F, Ziada KM, Aljohani S, Holmes DR, Mathew V. Contemporary trends in the management of aortic stenosis in the USA. See pages 921–928).

Patients with aortic stenosis are typically of older age. Clonal haematopoiesis of indeterminate potential (CHIP9), defined as the presence of an expanded somatic blood cell clone without other haematological abnormalities, was recently shown to increase with age and is associated with coronary disease and calcification. In their Fast Track manuscript ‘Clonal haematopoiesis in patients with degenerative aortic valve stenosis undergoing transcatheter aortic valve implantation’ Andreas Michael Zeiher and colleagues from the Goethe University in Frankfurt, Germany note that the most commonly mutated CHIP genes, DNMT3A and TET2, regulate inflammatory pathways of circulating leucocytes.10 The incidence of calcified aortic valve stenosis increases with age and correlates with chronic inflammation. They therefore assessed the incidence of CHIP and its association with inflammatory blood cell phenotypes in patients with aortic stenosis undergoing TAVI. Targeted amplicon sequencing for DNMT3A and TET2 was performed in 279 patients with severe aortic stenosis undergoing TAVI. Somatic DNMT3A- or TET2-CHIP-driver mutations with a variant allele frequency ≥2% were detected in one-third of the patients, with an age-dependent increase in the incidence from 25% in 55 to 69 year olds to 52.9% in 90 to 100 year olds. Patients with DNMT3A- or TET2-CHIP-driver mutations did not differ from patients without it in clinical parameters, concomitant atherosclerotic disease, blood cell counts, inflammatory markers, or procedural characteristics. However, those with DNMT3A- or TET2-CHIP-driver mutations had an increased medium-term all-cause mortality following TAVI. Differential myeloid and T-cell distributions revealed pro-inflammatory T-cell polarization in DNMT3A mutation carriers and increased pro-inflammatory non-classical monocytes in TET2 mutation carriers. Thus, acquired somatic mutations in the most commonly mutated CHIP-driver genes occur frequently in aortic stenosis and are associated with increased pro-inflammatory leucocyte subsets, and confer increased mortality following TAVI. These novel and intriguing findings are further discussed in an Editorial by Benjamin Ebert from the Harvard Cancer Center in Boston, Massachusetts, USA.11

Left ventricular pressure overload is associated with activation of the cardiac renin–angiotensin system, which may contribute to myocardial fibrosis and worse clinical outcomes. Thus, drugs interfering with this neurohumoral system are widely used in hypertension,12 after myocardial infarction,13 and in heart failure.14 In their manuscript entitled ‘Impact of renin–angiotensin system inhibitors on clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: an analysis of from the PARTNER 2 trial and registries’, Shmuel Chen from the Cardiovascular Research Foundation in New York, USA and colleagues sought to assess the association between treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) at baseline and clinical outcomes in patients with symptomatic, severe aortic stenosis undergoing TAVI in the PARTNER 2 trial and registries.15 A total of 3979 intermediate-, high-, or prohibitive-risk patients who underwent TAVI in the PARTNER 2 trial and registries were included in the study. At baseline, 43.6% were treated and 56.4% were not treated with an ACEI or ARB. Treatment with an ACEI or ARB was associated with lower 2-year all-cause mortality (18.6% vs. 27.5%), cardiovascular mortality (12.3% vs. 17.9%), and non-cardiovascular mortality (7.2% vs. 11.7%). ACEI or ARB treatment at baseline remained independently associated with a lower hazard of 2-year all-cause and cardiovascular mortality after multivariable adjustment and propensity score matching, Thus, in patients with severe symptomatic aortic stenosis, ACEI or ARB treatment at baseline was independently associated with a lower risk of 2-year all-cause and cardiovascular mortality and thus should be considered in such patients. These intriguing findings are complemented by an Editorial by Marc A. Pfeffer from the Brigham and Women’s Hospital in Boston, Massachusetts, USA.16

B-type natriuretic peptide (BNP) is a cardiac neurohormone that is secreted in response to ventricular volume expansion and pressure overload in patients with coronary artery disease,17 acute coronary syndromes,18 and heart failure.19 Although many patients with aortic stenosis have elevated filling pressures, there are conflicting data regarding BNP levels and outcomes after TAVI. In their article ‘Low and elevated B-type natriuretic peptide levels are associated with increased mortality in patients with preserved ejection fraction undergoing transcatheter aortic valve replacement: an analysis of the PARTNER II trial and registry’ Brian R. Lindman and colleagues from the Vanderbilt School of Medicine in Nashville, Tennessee, USA assessed the association between baseline BNP and adverse outcomes in 1782 patients with symptomatic, severe aortic stenosis and left ventricle ejection fraction or LVEF ≥50%, undergoing TAVI in the PARTNER 2 Trial and Registry (Figure 2).20 After adjustment, spline curves revealed a non-linear association between log-transformed BNP and all-cause and cardiovascular mortality in which both the lowest and highest values were associated with increased mortality. Two-year all-cause mortality rates for those with low, normal, moderately elevated, and markedly elevated baseline BNP were 20, 9.8, 17.7, and 26.1%, respectively. In adjusted models, compared with a normal baseline BNP, low BNP provided an adjusted hazard ratio (aHR) of 2.6, moderately elevated BNP provided an aHR of 1.6, and markedly elevated BNP provided an a HR of 2.1 which were associated with increased all-cause mortality, driven by cardiovascular mortality. Thus, in patients with severe symptomatic aortic stenosis and preserved LVEF undergoing TAVI, all-cause and cardiovascular mortality rates at 2 years were elevated in those with both low and markedly elevated BNP levels. These surprising findings are put into context in an Editorial by Speranza Rubattu from the School of Medicine and Psychology at Sapienza University in Rome Italy.21

Figure 2

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Adjusted association between log-transformed baseline B-type natriuretic peptide and the 2-year clinical outcomes. Multivariable Cox proportional hazards regression using a spline function to model log-transformed baseline B-type natriuretic peptide as a continuous metric for all-cause death (from Chen S, Redfors B, O‘Neill BP, Clavel M-A, Pibarot P, Elmariah S, Nazif T, Crowley A, Ben-Yehuda O, Finn MT, Alu MC, Vahl TP, Kodali S, Leon MB, Lindman BR. Low and elevated B-type natriuretic peptide levels are associated with increased mortality in patients with preserved ejection fraction undergoing transcatheter aortic valve replacement: an analysis of the PARTNER II trial and registry. See pages 958–969).

The editors hope that readers of this issue of the European Heart Journal will find it of interest.

With thanks to Amelia Meier-Batschelet for help with compilation of this article.

Categories: iatrika

πνευμονική αρτηριακή υπέρταση

Αρτηριακή Πνευμονική Υπέρταση: Μπορείς να βε

Υπάρχουν πολλοί τύποι πνευμονικής αρτηριακής υπέρτασης. Συχνά είναι ιδιοπαθής, ενώ μπορεί να συνδέεται με άλλη πάθηση, συνήθως καρδιακή η πνευμονική νόσο. Σε ορισμένες περιπτώσεις είναι κληρονομική.

Δημοσίευση: 26 Φεβρουαρίου 2020

Πηγή: iatronet.gr

Η Πνευμονική Αρτηριακή Υπέρταση (ΠΑΥ) είναι μια προοδευτική και σοβαρή νόσος, που πλήττει τα αιμοφόρα αγγεία τα οποία μεταφέρουν αίμα από την καρδιά στους πνεύμονες.

Οι πνευμονικές αρτηρίες συστέλλονται και στενεύουν, μειώνοντας τη ροή του αίματος προς τους πνεύμονες και αυξάνοντας την πίεση στην πνευμονική αρτηρία. Οποιοσδήποτε μπορεί να εμφανίσει πνευμονική αρτηριακή υπέρταση.

Ως αποτέλεσμα, επιβαρύνεται η καρδιά και ο ασθενής νιώθει δύσπνοια και κόπωση. Τα αρχικά συμπτώματα μπορούν να εμφανιστούν στις καθημερινές φυσικές δραστηριότητες, όπως το ανέβασμα μιας σκάλας, αλλά στη συνέχεια, καθώς η νόσος εξελίσσεται μπορεί να εμφανιστούν συμπτώματα και σε χαλάρωση

Για τους ανθρώπους που ζουν με τη νόσο, οι απλές καθημερινές εργασίες μπορεί να είναι εξίσου δύσκολες με την αναρρίχηση στην κορυφή του Έβερεστ.

Η ΠΑΥ επηρεάζει πολλές πλευρές της ζωής και ο ασθενής χρειάζεται χρόνο για να συνηθίσει τη νέα του ζωή, η οποία αλλάζει εντελώς.

Συμπτώματα

Τα συμπτώματα στα αρχικά στάδια μπορεί να μην είναι εμφανή για μήνες ή ακόμα και για χρόνια. Καθώς όμως η πάθηση εξελίσσεται, επιδεινώνονται.

Στα συμπτώματα περιλαμβάνονται:

• Δύσπνοια, αρχικά κατά την άσκηση και στο τέλος κατά την ανάπαυση
• Κούραση
• Ζαλάδα ή συγκοπικά επεισόδια
• Πίεση στο θώρακα ή πόνος
• Μειωμένη όρεξη
• Οίδημα στους αστραγάλους, στα πόδια και τελικά στην κοιλιά (ασκίτης)
• Κυανό χρώμα στα χείλη και στο δέρμα
• Ταχυπαλμία.

Παράγοντες κινδύνου

Ο κίνδυνος εμφάνισης πνευμονικής αρτηριακής υπέρτασης μπορεί να είναι μεγαλύτερος αν κάποιος

• Είναι νεαρής ηλικίας
• Είναι υπέρβαρος
• Έχει οικογενειακό ιστορικό της νόσου
• Έχει μια από ορισμένες νόσους που μπορούν να αυξήσουν τον κίνδυνο
• Χρησιμοποιεί ουσίες
• Λαμβάνει φάρμακα που καταστέλλουν την όρεξη
• Έχει υπαρκτό κίνδυνο εμφάνισης της πάθησης, όπως οικογενειακό ιστορικό και ζεί σε υψόμετρο.

Στις επιπλοκές περιλαμβάνονται θρόμβοι, αρρυθμία, αιμορραγία, υπερτροφία δεξιάς πλευράς της καρδιάς και καρδιακή ανεπάρκεια.

Η πρόγνωση και το προσδόκιμο επιβίωσης για κάποιον με την πάθηση βελτιώνεται, καθώς νεότερες επιλογές αγωγής γίνονται διαθέσιμες. Ωστόσο, η πρόγνωση μπορεί να εξαρτάται από την υποκείμενη πάθηση που την προκαλεί.

Σχετικά με την εξέλιξη της νόσου, το «λειτουργικό στάδιο» είναι ένας όρος που χρησιμοποιείται συχνά στην ΠΑΥ. Είναι μία από τις παραμέτρους που χρησιμοποιούνται για την αξιολόγηση και τη θεραπευτική προσέγγιση των ασθενών.

Η διάγνωση είναι σημαντική και πρέπει να γίνεται νωρίς. Ωστόσο, είναι δύσκολη και δεν γίνεται με μια μόνο εξέταση.

Μπορεί να γίνει δύσκολα αποδεκτή από τον ασθενή, ο οποίος μπορεί στο άκουσμά της να εμφανίσει, από σοκ και δυσπιστία έως θυμό ή λύπη. Πρέπει να ξέρει πως πολλοί ασθενείς είχαν την ίδια εμπειρία προσπαθώντας να προσαρμοστούν στη νέα κατάσταση.

Όμως, το ότι η διάγνωση έγινε και δόθηκε όνομα στην πάθηση, καθώς και ότι η αβεβαιότητα πέρασε, ενώ ο ασθενής ενημερώνεται και ότι μπορεί να αντιμετωπιστεί η νόσος με τη βέλτιστη θεραπεία, μπορεί να τον καθησυχάσει.

Η αγωγή μπορεί να συμβάλλει στη μείωση των συμπτωμάτων και στη βελτίωση της ποιότητα ζωής του ασθενούς. Περιλαμβάνει αντιμετώπιση της καρδιακής ή πνευμονικής  νόσου, φάρμακα, οξυγόνο και ορισμένες φορές μεταμόσχευση πνευμόνων.

Είναι σημαντικό η θεραπεία να αρχίσει όσο νωρίτερα γίνεται.

Μην ξεχνάτε, ότι αν πάσχετε από ΠΑΥ, εξακολουθείτε να είστε ο αυτός σας και κάνοντας προσαρμογές στην καθημερινή σας ζωή θα μπορέσετε να διατηρήσετε τον έλεγχο της ζωής σας.

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Categories: iatrika