1. BLOOD PRESSURE AND CHOLESTEROL THE BEGINNING OF YOUR END! Billy S. Arant, Jr., M.D., FASH Professor Emeritus, UTCOM-Chattanooga ASH Specialist in Clinical Hypertension Diplomate, American Board of Clinical Lipidology

2. VASCULAR DISEASEJUST THE FACTS 70 % of US deaths due to heart attack, stroke, heart failure and aneurysm--all vascular problems! ALL diabetics develop vascular disease and most are fat! Vascular disease causes serious long-term disability! Annual expenditures for vascular diseases of all causes exceed total costs of war in Iraq

3. RUN FROM THE CURE!

4. ARE YOU AT RISK?

5. BEYOND YOUR CONTROL Age Gender Race Heredity Prior cardiovascular event [Vascular abnormality] [Congenital heart defect]

6. STROKEBELT WD Hall, AHA 1999

7. WITHIN YOUR CONTROL Blood pressure Lipids Weight [waist] Blood sugar Tobacco Drugs Hormones

8. ELEVATED BLOOD PRESSURE earliest indication of trouble Normal is below 120/80 mmHg at any age BP >115/75 is earliest indicator of vascular risk Systolic (top #) most reliable indicator of risk Every drug that lowers BP may not reduce but actually increase risk Drugs that raise BP increase risk Lowering BP to normal with proven drugs reduces risk

9. Hi-Normal (n = 1794) 130 – 139/ 85 – 89 Normal* (n = 2185) 120 – 129/ 80 – 84 Optimal (n = 2880) < 120/80 Hazar d Ratio *P < 0.001 for trend across categories. 2. 5 1. 5 1. 0 Impact of High- Normal Blood Pressure on the Risk of Cardiovascular Disease Cumulative CVD Incidence, % Time, years Normal Optimal Hi-Normal Women Vasan RS, et al. N Engl J Med. 2001;345:1291–1297.

10. NORMAL BP <120/80 mmHg Robinson & Brucer: Arch Int Med 1939

11. NEXT, THE FAT IN YOUR ARTERIES or Atherosclerosis Cholesterol buildup Hardening of the arteries

12. THE GENESIS OF ATHEROSCLEROSIS unrelated to age

13. LIPID PROFILE Total cholesterol (good + bad) – HDL (good) retrieves LDL (bad) – LDL (bad) sticks to lining of artery – Non-HDL (LDL, VLDL, IDL) Total – HDL – Key to most vascular diseases (MI, stroke, PVD, ED) Triglycerides (animal and plant fat, glucose) – Insulin makes TG from excess glucose in blood – Used to make LDL and HDL in liver – Risks death from pancreatitis or NASH (fatty liver)

14. CHOLESTEROL normal values Triglycerides<150 mg/dl Total cholesterol<200 mg/dl HDL-C [good}>50 F; >40 M LDL-C [bad]<100 mg/dl [no risk] < 80 mg/dl [DM] < 70 mg/dl [CAD] Non-HDL-C [TC – HDL]<130 mg/dl Particle sizelarge fluffy Pattern A or BA

15. WHAT ARE THE SOURCES? All human cells make cholesterol – Cell membrane functions – Used to make bile – Steroid hormones Dietary sources – Eggs – Animal fat (meat, skin, milk, organs, lard) – Plant fat (saturated: palm, coconut, oleo) Bile salts – recycled Sugar changed to triglycerides for storage

22. CORONARY ARTERY KOREA Enos et al: JAMA 158:912, 1955 LAD 22yo White LAD 22yo Japanese

23. CORONARY ARTERIES VIETNAM McNamara et al: JAMA 216:1185, 1971 22 yo 50% RCA 3+ gross disease

24. CORONARY ARTERY DISEASE IN CHILDREN 10-14 yr olds Traumatic death >85 pct body weight 70% significant CAD w/ calcifications Bogalusa 2002

25. STORMIE JONES Homozygous FH

26. 1985 NOBEL LAUREATES LDL Receptor Michael Brown, M.D. Joseph Goldstein, M.D.

27. ATP III 2001, 2004 Scott Grundy, M.D., Ph.D.

28. TREATMENT OUTCOMES EVIDENCED-BASED adults

31. JUPITER TRIAL 2008 Low risk subjects – LDL-C 100-130 mg/dl – Elevated CRP [C-reactive protein] Rosouvastatin 20 mg daily v. placebo Reduced heart attack and strokes by 47% Drug company excluded from study Confirmed HPS 2003 with simvistatin

32. LDL-C: HOW LOW?

33. NOW FOR THE FAT AROUND YOUR WAIST!

34. VISCERAL OBESITY CT scans from men matched for BMI and total body fat Després J-P. Eur Heart J Suppl. 2006;8(suppl B):B4-12. Subcutaneous obesity Fat mass: 19.8 kg VFA: 96 cm 2 Visceral obesity Fat mass: 19.8 kg VFA: 155 cm 2 Visceral obesity drives CV risk progression independent of BMI

35. HEALTH CONSEQUENCES OF OBESITY not just a variation of normal anymore Hypertension Cholesterol Insulin resistance Diabetes mellitus Sleep apnea Coronary artery disease Stroke Erectile Dysfunction Gallbladder disease Osteoarthritis [joint replacement] Some cancers (uterine, breast, colon, prostate)

36. WHO HAS A WEIGHT PROBLEM ? Body mass index (BMI) for adults – > 25 kg/m ² overweight – > 30 kg/m² obese – > 35 kg/m² morbidly obese > 30 lbs over ideal body weight for height Waist measurement – women >33 overweight; >35 obese – men 40 obese

37. Obesity Trends* Among U.S. Adults BRFSS, 1985 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14%

38. Obesity Trends* Among U.S. Adults BRFSS, 1986 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14%

39. Obesity Trends* Among U.S. Adults BRFSS, 1987 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14%

40. Obesity Trends* Among U.S. Adults BRFSS, 1988 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14%

41. Obesity Trends* Among U.S. Adults BRFSS, 1989 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14%

42. Obesity Trends* Among U.S. Adults BRFSS, 1990 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14%

43. Obesity Trends* Among U.S. Adults BRFSS, 1991 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19%

44. Obesity Trends* Among U.S. Adults BRFSS, 1992 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19%

45. Obesity Trends* Among U.S. Adults BRFSS, 1993 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19%

46. Obesity Trends* Among U.S. Adults BRFSS, 1994 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19%

47. Obesity Trends* Among U.S. Adults BRFSS, 1995 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19%

48. Obesity Trends* Among U.S. Adults BRFSS, 1996 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19%

49. Obesity Trends* Among U.S. Adults BRFSS, 1997 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%

50. Obesity Trends* Among U.S. Adults BRFSS, 1998 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%

51. Obesity Trends* Among U.S. Adults BRFSS, 1999 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%

52. Obesity Trends* Among U.S. Adults BRFSS, 2000 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%

53. Obesity Trends* Among U.S. Adults BRFSS, 2001 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%–24% 25%

54. (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) Obesity Trends* Among U.S. Adults BRFSS, 2002 No Data <10% 10%–14% 15%–19% 20%–24% 25%

55. Obesity Trends* Among U.S. Adults BRFSS, 2003 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%–24% 25%

56. Obesity Trends* Among U.S. Adults BRFSS, 2004 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%–24% 25%

57. Obesity Trends* Among U.S. Adults BRFSS, 2005 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% 30%

58. Obesity Trends* Among U.S. Adults BRFSS, 2006 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% 30%

59. Obesity Trends* Among U.S. Adults BRFSS, 2007 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% 30%

60. Obesity Trends* Among U.S. Adults BRFSS, 2008 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% 30%

61. Obesity Trends* Among U.S. Adults BRFSS, 2009 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% 30%

62. Obesity Trends* Among U.S. Adults BRFSS, 2010 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% 30%

63. YOUR WEIGHT greatest morbid factor for health >60% of children and adults are overweight 1:3 children and adults are obese Costs >$100 billion in healthcare and lost productivity (50% paid by MCD + MC) Obese employee costs ~$8,000 extra/yr in missed days of work and healthcare Life expectancy of obese 5 year old is 47 yrs

64. LOVE IS BLINDNOT ! Survey of parents whose 6-11 yo child was obese – 43%about the right weight – 37%slightly overweight – 13%very overweight – 7%slightly underweight

66. HOW DID WE GET SO FAT SO FAST?

67. ENERGY BALANCE NRG in = expended = no body wt 3600 unanswered calories = +1 lb fat New fat comes mostly from sugar not fat!

69. UNANSWERED CALORIES 12 oz soda = run 1.25 miles 12 oz soda daily for 10 years – 36 g corn syrup = 144 kcal – 144 kcal x 365 days = 52,560 kcal – 3600 unanswered kcal = + 1 lb fat – 14.6 lb fat/yr or 146 lb/10 years!

72. BURNING EXTRA CALORIES BigMac, large fries, 32 oz drink Sedentary 12 yo must jog 3 hours to avoid weight gain if already/will ingest daily requirement for growth of 2200 kcal

73. UNANSWERED CALORIES 10 yo sedentary Requirements ~ 2270 kcal/day Pop Tart + OJ 8 oz 320 Pizza 2 sl + 24 oz DP + 2 Oreos1042 Chips 5 oz + 24 oz DP1050 Big Mac, Fries, 32 oz Coke1410 Popcorn + 32 oz Coke 540 Total kcal in 4362 required -2270 kcal net [1400 kcal from soda] +2192 Dilemma: Jog 4 hr 42 min or gain 9 oz fat

76. FAT KIDS become FAT ADULTS ! Fat Adults Spend Lots Of Money [theirs and ours] on food, health care, disability and death $1 Trillion annually

77. CAN YOU DO THIS?

78. RISKS OF OBESITY compounding risk Obesity BPDMCVDLipid OSA VASCULAR EVENT tobacco 2x O BP 2x

79. HT v. BMI in Blacks RS Cooper, AHA 1999

80. PREVALENCE OF HYPERTENSION IN ADOLESCENTS Sorof et al Am J Hypertension 16:217A, 2003

81. SUGAR Carbohydrates – Fruits – Vegetables – Grains Food additives – Cane or beet – High fructose corn syrup

82. GLUCOSE METABOLISM/DISPOSAL Dietary intake Insulin effect – Immediate use – Storage – Triglycerides

83. BLOOD SUGAR pre-diabetes and diabetes after 12 hr fast [water only] – normal <100 mg/dl – pre-diabetes100-125 mg/dl – diabetes>125 mg/dl 2 hr post-prandial or GTT – normal<140 mg/dl – pre-diabetes140-199 mg/dl – diabetes>200 mg/dl Hemoglobin A1C >6.5

84. Who has insulin resistance? DM2 1 HTN 3 Stroke 4 CHD 5 Refer to cardiol. 6 Age 40 to 74 7 1 Haffner et al. Diabetes. 1997. 2 McLaughlin et al. Am J Cardiol. 2005. 3 Reaven et al. N Engl J Med. 1996. 4 NIH. www.clinicaltrials.gov. 5 Lankisch et al. Clin Res Cardiol. 2006. 6 Savage et al. Am Heart J. 2005. 7 www.diabetes.niddk.nih.gov/. % Patients HDL + TG 2

85. Ticking clock hypothesis: Glucose abnormalities increase CV risk Nurses Health Study, N = 117,629 women, aged 30–55 years; follow-up 20 years (1976–1996) Hu FB et al. Diabetes Care. 2002;25:1129-34. Relative risk of MI or stroke* No diabetes Before diabetes diagnosis After diabetes diagnosis Diabetes at baseline *Adjusted n = 1508 diabetes at baseline n = 5894 new-onset diabetes

86. 1994 US Diabetes Trends - CDC

87. 1995 US Diabetes Trends - CDC

88. 1996

89. 1997

90. 1998

91. 1999

92. 2000

93. 2001

94. 2002

95. 2003

96. 2004

97. 2005

98. 2006

99. 2007

100. 2008

101. 2009 US Diabetes Trends - CDC

102. Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes Obesity (BMI 30 kg/m 2 ) Diabetes 1994 2000 No Data 26.0% No Data 9.0% CDCs Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 2009 Diabetes Obesity

103. 90% of patients with newly diagnosed diabetes are overweight or obese Geiss LS et al. Am J Prev Med. 2006;30:371-7. Obese (BMI 30) Overweight (BMI 25 to <30) Diabetes patients with BMI 25 kg/m 2 (%) National Health Interview Survey, 2003; N 31,000 aged 18 to 79 years 90%

104. Narayan et al, JAMA, 2003 Estimated lifetime risk of developing diabetes for individuals born in the United States in 2000

105. DIABETES MELLITUS risk equivalent to previous heart attack Two types – DM1 insulin deficient, normal weight [10%] – DM2 insulin resistant, overweight [90%] Juvenile v. adult type 2:3 people with CAD have DM, half undiagnosed DM is risk equivalent to previous heart attack May take 5-10 yrs of pre-diabetes before diabetes recognized Diabetes costs $132 billion in medical expenses and lost productivity (twice that of non-diabetics)

106. COMPLICATIONS OF DIABETES diabetics die from vascular disease Macrovascular disease – coronary artery disease [heart] – cerebrovascular disease [stroke] – peripheral vascular disease [legs] amputations Microvascular disease – blindness [eyes] – renal failure [kidneys] – neuropathy [sensation] – erectile dysfunction

107. DIABETES MELLITUS 2 Complication of obesity almost always [90%] Preventable if normal waist maintained Possible to cure by losing weight/waist Leading cause of – kidney failure >50% on dialysis – Blindness – Associated with 2/3 of heart attacks Economic disaster [$1 trillion annually]

108. OBSTRUCTIVE SLEEP APNEA Suspect when – Snoring – Stops breathing – Tired when awake despite 8 hours of sleep – Yawns while awake – Restless sleep – bedding disaray – Obese – Hypertension – systemic and pulmonary

109. TOBACCO nicotine toxic to vascular lining

110. INTERHEART: Any smoking increases CV risk Teo KK et al. Lancet. 2006;368:647-58. Odds ratio for first MI* *vs never smoked N = 27,098 from 52 countries Cigarettes smoked (n/day) Never1–23–45–67–89–1011–1213–1415–1617–1819–2021 -0.75 1 2 4 8

112. DRUGS

113. DRUGS CAN INCREASE RISK Recreational drug use – Amphetamines, cocaine Decongestants increase BP – Pseudophedrine Hormones: estrogen, testosterone NSAIDs [ibuprofen,naproxen,celebrex] – 15,000 deaths/yr to GI bleeding – Raise BP – Reduces kidney function – Reverses aspirin benefit to prevent blood clots

114. PROSTAGLANDINS [inhibition] Mediators of inflammation [reduces pain/retards healing] Vasodilators to regulate organ blood flow [VC] – HTN, AMI/angina, CVA, CHF, ARF [intravascular volume] Alters renal functions – RBF, GFR, loop NaCl, AVP/water in CD GI mucus production to protect mucosa [bleed] READ PI/LABEL! REGARD TORT POTENTIAL!

115. IBUPROFEN PRECAUTIONS OTC – no longer than 3 days for fever Allergy to NSAID including ASA DO NOT take aspirin or acetaminophen w/ ibuprofen unless MD tells you to DO NOT take if fluid intake is unreliable Hx heart liver GI or renal disease, HBP, stroke Pregnant, plans or breast feeding Surgery planned If taking warfarin, ß-blockers, CYA, digoxin, diuretics, lithium, metotrexate, phenytoin DO NOT drive or operate machinery until… NO alcohol w/ ibuprofen

116. OTHER FACTORS your doctor may not be measuring Uric acid [gout, stones]< 6 mg/dl – Stroke risk increased when values higher – Seems to facilitate cholesterol build up – Risk equivalent to heart attack – Rx- production or excretion Homocysteine [dementia]< 9 mg/dl – Stroke risk increased when values higher – Treatment with folic acid and B high dose C-reactive protein [CRP]< 1 mg/dl – indicates vascular inflammation and risk of a cardiovascular event Kidney function [eGFR] >60 ml/min/1.73m² – Reduced kidney function increases CV risk – Hypertension destroys kidneys [20% dialysis patients]

117. ISCHEMIC STROKE V. PLASMA HOMOCYSTEINE Sacco et al NOMAS Stroke 35:2663, 2004

118. CAD SURVIVAL V. HOMOCYSTEINE Nygard et al; NEJM 337:230, 1997

119. CV EVENTS v. eGFR Go et al; NEJM 351:1296, 2004

120. SO, WHATCHA GONNADO ABOUT IT?

121. KNOW YOUR NUMBERS dont leave it to your doctor BP <120/80 + treatment – drugs that affect angiotensin [ACEi or ARB] Cholesterol to goal for your specific risk – high HDL reduces risk >50 F; >40 M – low LDL reduces risk <100 no risk; <80 DM, <70 prior CVE – non-HDL (TC – HDL) is total bad cholesterol <130 no risk, <100 w/ risk – triglycerides <150 but lower is better – dont wait for diet and exercise alone to work – statins proven to reduce risk independent of LDL Fasting blood sugar <100 (A1C <6.0) + DM Waist <33 F; <37 M CRP < 1.0 Uric acid < 6.0 Homocysteine < 9.0 Kidney function [eGFR] > 60

122. Treat the problems you have with outcome-proven drugs Blood pressure – include ACEi or ARB Statin Niacin Omega 3 s Anticoagulant – aspirin, coumadin Antiarrhythmic- beta blocker

123. HOW TO LOSE WEIGHT works every time! Know what youre eatingread the label! Eat less – Maintain normal weight m-1800 kcal, f-1500 kcal – Lose weight reduce calories by > 300 kcal/day – portion control Eat healthy – Protein: fish, eggs, less meat, low fat dairy, beans – Fat: no trans, less saturated, more olive or canola oil – Carbs: fresh fruits, no juices, colored vegetables + cauliflower, whole grain bread or cereal, no high fructose corn sugar ever, use sugar substitutes – Adkins, South Beach, Sugar Busters are healthy Exercise more – 30 minutes 3 times a day to start, then daily (walking will burn 1.25 lb fat/month Sleep 8 hours every night

124. HOW TO FAIL LONG-TERM WEIGHT LOSS! Choose anything other than whats on the previous slide Try advertised products for diet or exercise Buy something sold in doctors office or with some doctors name on it Get your advice from Dr. Feelgood Believe everything the nutritionist tells you

125. ANTIDOTE TO VASCULAR EVENT reducing your risk Can you afford to survive? Family history of vascular disease? Have you had vascular screening? What about your weight/waist? Do you have erectile dysfunction? Do you abuse tobacco? Do you exercise regularly? Do you take an aspirin daily? Do you take any drug that raises BP? Still taking hormones? Do you know your numbers?

126. WHAT TO DO? if you think youre having a heart attack or stroke Chew and swallow 325 mg aspirin Call 911 Ask to be taken to a certified Heart or Stroke Center Plan ahead – Determine the heart or stroke center closest to you – Ask if a neurologist who is a stroke specialist will be available to you – Clot busters and Merci retriever to remove blood clots – Confirm that door to cath lab time is <60 minutes

127. HOW TO IMPROVE YOUR CHANCES OF ACTUALLY HAVING A VASCULAR EVENT? Ignore symptoms or signs Have a previous TIA, stroke or heart attack Ignore your blood pressure or skip your medicine to save money Have a sibling or parent with cerebral aneurysm at young age Dont take blood thinners for atrial fibrillation Treat your diabetes by diet and exercise Smoke, chew or dip liberally Weight no problem as long as you dont look fat Lower your cholesterol by diet and exercise only Dont take daily aspirin >40 yrs of age Dont have vascular screening >50 years of age Take NSAID for pain and decongestants for cold/sinus problem Get off the hormonesembrace menapause Be blood kin to someone who has vascular disease Active sex life with uncontrolled high blood pressure Be black Live in the Southeastern USA Avoid certified heart or stroke centers

128. MOST VASCULAR EVENTS ARE PREVENTABLE !

129. THANK YOU !