The unholy trinity of stroke risk: Sleep Apnea, Obesity, and Hypertension

Transcription

1 The unholy trinity of stroke risk: Sleep Apnea, Obesity, and Hypertension P. Timothy Pollak, MD, PhD Professor of Medicine, Cardiac Sciences & Pharmacology

2 A Case of Atrial Fibrillation 62 y man referred with palpitations, fatigue for the last 6 months EKG showed atrial fibrillation rate 145 Given diltiazem and metopropol, but continues to feel restricted in daily abilities Had been taking amlodipine 5 mg/d for 10 y BP is 140/95

3 A Case of Atrial Fibrillation - 2 Diagnosed with glucose intolerance & high cholesterol in last year BMI is 30 Admits to snoring and is tired every day Wants to have an ablation so he will feel better How do you council and treat this patient

4 Objectives At the end of the presentation the listener should understand: The common risks for developing A. fib The issues involved in choosing therapy The potential roles for non-pharmacological, antihypertensive, and rhythm control therapy in A. Fib

5 A. fib - a problem of aging Prevalence grows to 9% by the 8th decade of life 5.6 million patients in the USA by mid-century May impact quality of life comparable to malignancy Increased embolic events (10-15% of strokes) Reduced cardiac function Clinical burden in a 2-y period: 14 office visits; 12 outpatient visits; 2 admissions to hospital; 1 ER visit; 1.9-fold increase in risk of mortality

6 The unholy trinity of aging Aging Obesity Inflammatory Cytokines Hypertension Metabolic Syndrome Atrial Fib Catacholamines Angiotensin Sleep Apnea Diseases of valves & atrial anatomy

7 Obesity - A problem of Aging Currently, > 64% of US adults overweight or obese Prevalence of obesity in persons > 60 y in: 1990 was 24% 2000 was 32% 2010 will be 40% projected by birth cohort Arterburn DE, et al. The coming epidemic of obesity in elderly Americans. J Am Geriatr Soc 2004;52: % of pop will be > 65 y in 2030 (2x that in 2000)

8 Hypertension - a problem of Aging National Health and Nutrition Examination Survey Age Hypertension (NHANES ) % % % % % % At age 55, remaining normotensives have 90 % chance of developing hypertension. Sever, P. New Hypertension Guidelines from the National Institute for Health & Clinical Excellence and the British Hypertension Society. Journal of the Renin Angiotensin Aldosterone System 7(2):61-3, June 2006

9 Sleep Apnea - a problem of Aging 40% of adults are habitual snorers by age 50 by middle age, 9% of women + 24% of men meet the minimum criteria for obstructive sleep apnea Bixler EO et al. Effects of age on sleep apnea in men: Am J Respir Crit Care Med 1998;157: Veldi M et al. Ageing, soft-palate tone and sleeprelated breathing disorders. Clinical Physiology 2001;21:

10 Sleep and diabetes Yaggi HK et al. Sleep Duration as a Risk Factor for the Development of Type 2 Diabetes. Diabetes Care 2006;29: Suppression of slow-wave sleep in healthy young adults significantly decreases their ability to regulate bloodsugar levels and increases the risk of type 2 diabetes. University of Chicago Medical Center. "Lack Of Deep Sleep May Increase Risk Of Type 2 Diabetes." ScienceDaily 2 January < Basta M et al. Metabolic abnormalities in obesity and sleep apnea are in a continuum. Sleep Med 2007;8: 5-7.

11 Relationship Between BMI and Risk of Type 2 Diabetes 93.2 Age-Adjusted Relative Risk Men Women <22 < Chan J et al. Diabetes Care 1994;17:961. Colditz G et al. Ann Intern Med 1995;122: Body Mass index (kg/m 2 ) Slide Source:

12 Obesity - Sleep - Hypertension Half of patients with essential hypertension have obstructive sleep apnea -- half of patients with OSA have essential hypertension. Silverberg DS et al. Treating Obstructive Sleep Apnea Improves Essential Hypertension and Quality of Life. Am Fam Physician 2002;65: Obesity causes sympathetic and renin-angiotensin activation. Davy KP, Hall JE. Obesity and hypertension: two epidemics or one? Am J Physiol Regul Integr Comp Physiol 2004; 286: R803-R813.

13 Obesity - Sleep - Hypertension Dose response association between sleep-disordered breathing at base line and the presence of hypertension 4 years later independent of known confounding factors. Findings suggest sleep-disordered breathing is a risk factor for hypertension and consequent cardiovascular morbidity in the general population. Peppard PE et al. Prospective study of the association between sleepdisordered breathing and hypertension. N Engl J Med. 2000;342:

14 Obesity - Sleep - Hypertension Apnea and the Risk of Coexisting Hypertension Nieto FJ et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. JAMA.2000:283:

15 Obesity - sleep TV - In last 40 y, average sleep time cut 2 hours. 73% more obesity in persons who sleep < 4 h/night 71% increased ghrelin : leptin ratio in persons who sleep < 4 h/night compared to 10 h in bed study - significant sleep debt triggers metabolic and endocrine changes mimicking aging study - inadequate sleep fosters insulinresistance, a risk factor for Type 2 diabetes. "Sleep Loss Boosts Appetite, May Encourage Weight Gain." ScienceDaily 7 Dec

16 Obesity - sleep Prevalences of overweight and obesity at age 21 years increased with increasing frequency of sleeping problems at ages 2-4 years in a cohort of 2494 individuals born between 1981 and Abdullah Al Mamun. Am J Epidemiol. 2007;166: University of Queensland, Brisbane, Australia Federal Motor Carrier Safety Administration estimates 30% of commercial truck drivers suffer from some form of OSA - the two major factors that put drivers at risk for sleep apnea are age and degree of obesity.

17 Treatment of Atrial Fibrillation

18 Key therapeutic decisions Therapy must address: Thromboembolic risk Cardiac function Patient symptoms The days of quinidine plus digoxin are over Mortality with quinidine is 3 x placebo Coplen SE, et al. Circulation 1990;82:

19 CHADS 2 Score and Risk of Stroke JAMA 2001;285:2864

20 Balance in decisions Primum Non Nocere BUT all therapy carries risk! Anticoagulation - risky business = big return Rhythm control - risky business =? return benefit to cardiac function? symptoms? superiority to rate control? Decisions are swayed by knowledge

21 Risk - Benefit Therapy cannot help if there is no benefit to gain Therapy cannot help if adverse effects are severe and frequent Clearly, the more the potential benefit and the less the potential adversity, the more likely the scale will tip in favor of using that therapy.

22 Therapeutic strategies Rate Control: Avoid proarrhythmia Avoid other toxic drug effects Avoid intermittent A. fib due to inefficacy Increase compliance & lower cost of Rx Rhythm Maintenance: Better cardiac output Better rate control Fewer symptoms?reduced tendency for coagulation

23 AFFIRM Trial Atrial Fibrillation Follow-up Investigation of Rhythm Management Randomized evaluation of A fib treatment by rate control vs. rhythm control and anticoagulation 4,160 patients followed for an average of 2.6 years Primary Endpoint = total mortality in 2 groups

24 AFFIRM Population Inclusion criteria: > 1 AF episode > 6 h on ECG in last 6 weeks > 65 yo + > 1 clinical risk factor for stroke including: HTN, DM, CHF, TIA, CVA, EF<40% Eligible for RATE or RHYTHM control not too symptomatic for rate control not too long in A fib or antiarrhtymic adverse

25 AFFIRM therapies All patients anticoagulated Rate control beta blockers, verapamil, diltiazem, digoxin or combinations dosage adjusted to achieve target heart rates innovative therapies after failure > two drugs Sinus Rhythm amiodarone, sotalol, propafenone, flecainide, quinidine, moricizine, disopyramide, procainamide or combinations. AV nodal blocking drugs and anticoagulation as indicated multiple cardioversions

26 AFFIRM Results After average of 3.5 y follow-up 306 deaths in rate-control vs. 356 in the rhythm-control rhythm-control - more hospitalization, more adverse drug effects Conclude: Rate control at least as good as rhythm control and should be considered as a primary strategy. Note: majority of strokes occurred after warfarin had been stopped or INR became subtherapeutic Wyse DG, N Engl J Med 2002;347:

27 Treating the underlying causes of Atrial Fib

28 Atrial fibrillation and hypertension Atrial fibrillation is the most prevalent clinically significant cardiac arrhythmia and a major risk factor for stroke Hypertension is responsible for more cases of AF than any other risk factor Experimental and clinical studies suggest that inhibition of the renin-angiotensin system may have a role in preventing AF

29 Time to occurrence of Afib in SOLVD Trial 1.00 Freedom from atrial fibrillation Enalapril Placebo p < Time (years) Circulation 2003; 107:

30 Valsartan reduces new-onset AF in VAL-HeFT 0.15 Estimated probability of AF Placebo Valsartan Months of follow-up Maggioni et al Am Heart J 2005;149:548-57

31 Hypertension in AF Better hypertension therapy = better AF therapy Weight loss = better hypertension therapy Weight loss = better airway control at night Identify and treat OSA = better hypertension therapy Modify RAAS especially in the face of CHF EP and remodeling effects benefit AF therapy BP in elderly may not reach goal without addition of CCB + thiazide Non-DHP CCB and beta-blockers tend to cause fatigue Other classes, Alpha-blocker, central agents - little evidence

32 AF - amiodarone works better A fib modifies atrial electrical properties Promotes occurrence and maintenance of A fib!l-type Ca2+ current reduces action potential duration Nattel S. Cardiovasc Res 1999;42: Amiodarone effective against A Fib promotion Prevents EP and biochemical consequences of remodeling Reverses remodeling 4 days of atrial tachy pacing. Shinagawa K, et al. Circulation 2003;107: Superior efficacy of amiodarone proven in CTAF & AFFIRM.

33 AF - dronedarone easier to use Properties similar, but DIFFERENT to amiodarone No iodoine Pharmacokinetic properties - 1/60 the half-life More GI effects - taken BID Sensitive to CYP450 interactions Half as effective as amiodarone in Euridosys Trial Cost $4-5 per day

34 AF - adjuvants to amiodarone RAAS is a mediator of atrial remodeling in atrial fibrillation. Group I - 75 on amiodarone vs. II 79 on amio + irbesartan Patients remaining free of A fib (55.91% vs %, P=0.007) Madrid AH, et al. Circulation 2002;106:331-6 Amiodarone plus beta-blocker treatment after acute MI pooled database EMIAT and CAMIAT amiodarone plus beta-blockers not hazardous beta-blocker therapy should be continued if possible in patients in whom amiodarone is indicated. Boutitie F, et al. Circulation 1999;99:

35 Back to the case 62 y man referred with palpitations, fatigue for the last 6 months EKG showed atrial fibrillation rate 145 Given diltiazem and metopropol, but continues to feel restricted in daily abilities Had been taking amlodipine 5 mg/d for 10 y BP is 140/95

36 Considerations Anticoagulation? Duration of a fib? Urgent conversion? Optimization of underlying risk factors Therapy for hypertension - CCB in Elderly? RAAS and sympathetic intervention? Would you use amiodarone if it had no AE?