1. Carlos M. Nieves La Cruz, M.D., F.A.C.C. Interventional Cardiologist
Prevención, Diagnóstico y Manejo de Enfermedades Cardiovasculares e Hipertensión
Carlos M. Nieves La Cruz, M.D., F.A.C.C.
Interventional Cardiologist

2. Disclosure
I, Carlos M. Nieves La Cruz or my spouse, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation

3. Outline and Objectives
Review recent AHA statistics of CV disease
Define Primary and Secondary prevention and the risk factors for CV disease
Diabetes Mellitus and Cardiovascular Disease
Smoking and CV disease
Compare the 2014 JNC-8 and AHA Guidelines and evidence for the treatment of Hypertension
Review the 2013 AHA/ACC Guidelines and evidence for the Treatment of Blood Cholesterol in Adults

4. Overview of Cardiovascular Disease
Prevalence (in millions)
Total
85.6
High Blood Pressure
77.9
Coronary Heart Disease
15.5
Heart Failure
5.7
Stroke
6.6
AHA 2016 Statistics Update

5. Other Cardiovascular Diseases Valvular Heart Disease 2.5%
Prevalence or Incidence
Valvular Heart Disease
2.5%
Congenital CV Defects
(8/1000 births)
Rheumatic Fever/RHD
20,000
Cardiomyopathy
HCM 500,000
Disorders of Heart Rhythm (AF)
5.1 millions
Sudden Cardiac Arrest
356,000/ year
Subclinical atherosclerosis (CAC)
32.0 to 52.9%
Diseases of the Aorta (AAA)
1.2% to 12.5%
Peripheral Arterial Disease
8.5 millions
Venous Thromboembolic Disease
300, ,000/yr
Pulmonary Heart Disease/PAH
15-50/million

6. Prevalence of cardiovascular disease in adults ≥20 years of age by age and sex (National Health and Nutrition Examination Survey: 2009–2012).
Prevalence of cardiovascular disease in adults ≥20 years of age by age and sex (National Health and Nutrition Examination Survey: 2009–2012). These data include coronary heart disease, heart failure, stroke, and hypertension. Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

7. Incidence of cardiovascular disease (coronary heart disease, heart failure, stroke, or intermittent claudication; does not include hypertension alone) by age and sex (Framingham Heart Study, 1980–2003).
Incidence of cardiovascular disease (coronary heart disease, heart failure, stroke, or intermittent claudication; does not include hypertension alone) by age and sex (Framingham Heart Study, 1980–2003). Source: National Heart, Lung, and Blood Institute.3
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

8. Deaths attributable to cardiovascular disease (United States: 1900–2011).
Deaths attributable to cardiovascular disease (United States: 1900–2011). Cardiovascular disease (International Classification of Diseases, 10th Revision codes I00–I99) does not include congenital heart disease. Before 1933, data are for a death registration area and not the entire United States. Source: National Center for Health Statistics.
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

9. Projected total costs of cardiovascular disease (CVD), 2015 to 2030 (2012 $ in billions) in the United States.
Projected total costs of cardiovascular disease (CVD), 2015 to 2030 (2012 $ in billions) in the United States. CHD indicates coronary heart disease; CHF, congestive heart failure; and HBP, high blood pressure. Unpublished data tabulated by the American Heart Association using methods described in Heidenreich et al.8
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

10. Projected direct costs of total cardiovascular disease by type of cost
(2010 $ in billions).
Projected direct costs of total cardiovascular disease by type of cost (2010 $ in billions). Unpublished data tabulated by the American Heart Association using methods described in Heidenreich et al.8
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

11. Cardiovascular disease (CVD) deaths versus cancer deaths by age (United States:2011)
Cardiovascular disease (CVD) deaths versus cancer deaths by age (United States: 2011). CVD includes International Classification of Diseases, 10th Revision codes I00 to I99 and Q20 to Q28; cancer, C00 to C97. Source: National Center for Health Statistics.
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

12. Cardiovascular disease and other major causes of death for Hispanic or Latino males and females (United States: 2011).
Cardiovascular disease and other major causes of death for Hispanic or Latino males and females (United States: 2011). A indicates cardiovascular disease plus congenital cardiovascular disease (International Classification of Diseases, 10th Revision codes I00–I99, Q20–Q28); B, cancer (C00–C97); C, accidents (V01–X59 and Y85–Y86); D, diabetes mellitus (E10–E14); E, chronic lower respiratory disease (J40–J47); and F, Alzheimer disease (G30). Number of deaths shown may be lower than actual because of underreporting in this population. Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

13. 289,747
8.7 % de la poblacion

17. Percentage breakdown of deaths attributable to cardiovascular disease (United States: 2011).
Percentage breakdown of deaths attributable to cardiovascular disease (United States: 2011). Total may not add to 100 because of rounding. Coronary heart disease includes International Classification of Diseases, 10th Revision (ICD-10) codes I20 to I25; stroke, I60 to I69; heart failure, I50; high blood pressure, I10 to I15; diseases of the arteries, I70 to I78; and other, all remaining ICD-I0 I categories and Q20 to Q28. *Not a true underlying cause. With any-mention deaths, heart failure accounts for 36% of cardiovascular disease deaths. Source: National Heart, Lung, and Blood Institute from National Center for Health Statistics reports and data sets.
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

18. PR Heart Attack Study

19. Estimated average 10-year cardiovascular disease risk in adults 50 to 54 years of age according to levels of various risk factors (Framingham Heart Study).
Estimated average 10-year cardiovascular disease risk in adults 50 to 54 years of age according to levels of various risk factors (Framingham Heart Study). BP indicates blood pressure; and HDL, high-density lipoprotein. Data derived from D’Agostino et al43 with permission of the publisher. Copyright © 2008, American Heart Association.
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

20. Prevalence (%) of coronary calcium: US adults 45 to 84 years of age.
Prevalence (%) of coronary calcium: US adults 45 to 84 years of age. P< across ethnic groups in both men and women. Data derived from Bild et al.8
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

21. Prevalence (%) of coronary calcium: US adults 33 to 45 years of age.
Prevalence (%) of coronary calcium: US adults 33 to 45 years of age. P< across race-sex groups. Data derived from Loria et al.7
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

22. Levels of Prevention
Primordial Prevention is defined as prevention of risk factors themselves, It addresses broad health determinants in the population level or selected groups Primary Prevention is defined as modification or reduction of risk factors in order to prevent or delay the onset of disease. Generally it targets specific causes and risk factors for specific diseases. Examples are smoking cessation and vaccination. Secondary Prevention includes therapy to reduce recurrent events and decrease mortality in patients with established disease Tertiary Prevention seeks to soften the impact caused by the disease on the patient’s function, longevity and quality of life.

24. Risk Factors for Atherosclerosis
Genetic, family history (premature ASCVD)
Age men > 45, women > 55
Male gender or post menopausal women
Race: African American, South Asian
Obesity
Sedentary lifestyle
Diabetes Mellitus, Metabolic syndrome
Hypertension
Hypercholesterolemia
Smoking
Mental Stress, Depression

25. Other Risk Factors for Atherosclerosis
CRP
Lp(a)
Homocysteine
Small dense LDL-C
Fibrinogen
Proteinuria
PAI-1/t-PA
Lp-PLA2
ABI
CKD
ESRD
CTD (RA, SLE)
Corticosteroids
HIV
Antiretrovirals
Low testosterone
Lack of sleep/OSA
PAD

26. Modifiable Risk Factors for Atherosclerosis
Obesity
Sedentary lifestyle
Diabetes Mellitus, Metabolic syndrome
Hypertension
Hypercholesterolemia
Smoking
Stress, Depression

27. AHA Strategic Impact Goals
“By 2020, to improve the cardiovascular health of all Americans by 20%, while reducing deaths from CVDs and stroke by 20%.”
Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Associations’s strategic Impact Goal through 2020 and beyond. Circulation. 2010;121:

28. AHA 7 Metrics of Cardiovascular Health
Diet quality
Physical activity
Smoking
BMI
Blood Cholesterol
Blood Pressure
Blood Glucose

30. Prevalence (unadjusted) estimates for poor, intermediate, and ideal cardiovascular health for each of the 7 metrics of cardiovascular health in the American Heart Association 2020 goals, US children aged 12 to 19 years, National Health and Nutrition Examination Survey (NHANES) 2011 to *Healthy diet score data reflects 2009 to 2010 NHANES data.
Prevalence (unadjusted) estimates for poor, intermediate, and ideal cardiovascular health for each of the 7 metrics of cardiovascular health in the American Heart Association 2020 goals, US children aged 12 to 19 years, National Health and Nutrition Examination Survey (NHANES) 2011 to *Healthy diet score data reflects 2009 to 2010 NHANES data.
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

31. Prevalence (unadjusted) estimates of poor, intermediate, and ideal cardiovascular health for each of the 7 metrics of cardiovascular health in the American Heart Association 2020 goals among US adults aged 20 to 49 years and ≥50 years, National Health and Nutrition Examination Survey (NHANES) 2011 to *Healthy diet score data reflects 2009 to 2010 NHANES data.
Prevalence (unadjusted) estimates of poor, intermediate, and ideal cardiovascular health for each of the 7 metrics of cardiovascular health in the American Heart Association 2020 goals among US adults aged 20 to 49 years and ≥50 years, National Health and Nutrition Examination Survey (NHANES) 2011 to *Healthy diet score data reflects 2009 to 2010 NHANES data.
Dariush Mozaffarian et al. Circulation. 2015;131:e29-e322
Copyright © American Heart Association, Inc. All rights reserved.

32. JNC 7: New BP Classifications
Slide ID: 7788
JNC 7 is a detailed document produced by a committee that applied broad expertise in developing a valuable guideline for all clinicians who treat patients with high BP.
In contrast to the classic concept that normal BP is < 140/90 mm Hg, normal BP in adults is defined as < 120/80 mm Hg, above which the risk of CV events increases.
Pre-hypertension, or high-normal BP, is 120/80 mm Hg to 139/89 mm Hg, and risk in patients in this group can be lowered by lifestyle modification comprising weight reduction, reduced sodium intake, regular physical activity, and avoidance of excessive alcohol consumption.
This new guideline presents a number of updated concepts that improve our understanding of hypertension as a CV risk factor and current approaches to treatment. Thus, clinical trials have demonstrated that antihypertensive therapy can reduce the incidence of stroke by 35%-40%, MI by 20%-25%, and heart failure by more than 50%.
JNC 7 emphasizes that a clinician's judgment is foremost in managing hypertensive patients. The guidelines present the scientific basis of antihypertensive therapy and the physician's application of this evidence to individual patients represents the art of medicine. Adherence to these principles can diminish the continuing "knowledge-practice gap" in the management of CV risk factors and contribute to the ultimate goal of stemming the tide of CVD.
Reference
Chobanian AV et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:

33. Cardiovascular Mortality Risk Doubles With Each 20/10 mm Hg BP Increment*
Slide ID: 7799
Throughout middle and old age, a person’s usual BP is strongly and directly related to CVD mortality, with no evidence of a threshold, down to at least 115/75 mm Hg.
In this meta-analysis, information was obtained regarding the usual BP and causes of death for 1 million adults without known CVD at the time of enrollment in 61 prospective, observational BP studies.
The analysis involved a correction for potential regression dilution bias by relating mortality during each decade of age at death to the estimated usual BP at the start of that decade.
Throughout the BP range > 115/75 mm Hg to 175/105 mm Hg, usual BP was found to be more strongly related to CVD than previously estimated.
At ages years, each increase of 20 mm Hg usual systolic BP (or 10 mm Hg usual diastolic BP) was associated with more than double the rate of stroke death and double the rate of death from CHD and other vascular causes.
The age-specific associations were similar for men and women.
Extrapolating from these data, a 10 mm Hg lower usual systolic BP or a 5 mm Hg lower usual diastolic BP throughout middle age would be associated with an approximate 40% lower risk of stroke death and an approximate 30% lower risk of death from CHD.
References
Chobanian AV et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:
Lewington S et al. Lancet. 2002;360:

34. Hypertension: A Risk Factor for Cardiovascular Disease
Slide ID: 7796
A prospective analysis of the 36-year follow-up data from the Framingham Heart Study demonstrated that hypertension (BP ≥ 140/90 mm Hg) is an important risk factor contributing to all major atherosclerotic CVD outcomes, including CHD, stroke, peripheral artery disease, and heart failure.
Hypertension is one of the most prevalent and powerful contributors to CVD and is an independent risk factor for heart attack, heart failure, stroke, and kidney disease.
Because of the high prevalence of hypertension in the general population, approximately 35% of atherosclerotic CVD events may be attributable to hypertension.
As shown in this figure, hypertension imparts a 2-fold to 3-fold increase in the risk for major CVD events. This increased risk occurs among both men and women.
Reference
Kannel WB. JAMA. 1996;275:

35. MRFIT: Elevation of SBP Exerts Greater Effects on Coronary Artery Disease Mortality
Slide ID: 7800
Data from the Multiple Risk Factor Intervention Trial (MRFIT) of 316,099 men were analyzed to assess the influence of BP and other risk factors on death from coronary artery disease (CAD).
Differences in death rates due to CAD among diastolic BP categories for each systolic BP category were small, particularly for subjects with diastolic BP < 90 mm Hg. However, a strong risk gradient was evident for systolic BP for each diastolic BP category.
A strong graded relationship between systolic BP > 110 mm Hg and diastolic BP > 70 mm Hg and CAD mortality was discerned. Systolic BP was a stronger predictor of death due to CAD than was diastolic BP in all age groups. The investigators emphasized that their findings, together with the results of clinical trials, offered strong support for intensified preventive efforts.
Reference
Neaton JD, Wentworth D, for the Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992;152:56-64.

36. JNC 8
2014 Evidence-Based Guidelines for the Management of High Blood Pressure in Adults
JAMA. 2014;311(5):
Online December 18, 2013

37. JNC 8: Graded Recommendations
A – Strong evidence B – Moderate evidence C – Weak evidence D – Against E – Expert Opinion N – No recommendation

38. Diabetes: ACCORD – Major CV Events
ACCORD Study Group. NEJM 2010

39. Effect of Blood Pressure Control
Diabetes Mellitus:
Effect of Blood Pressure Control
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial
4,733 diabetic patients randomized to intensive BP control (target SBP <120 mm Hg) or standard BP control (target SBP <140 mm Hg) for 4.7 years
Intensive BP control in DM does not reduce a composite of adverse CV events, but does reduce the rate of stroke
HR=0.88
95% CI ( )
HR=0.59
95% CI ( )
Nonfatal MI, nonfatal stroke, or CV death
Total Stroke
In the ACCORD BP trial, 4,733 diabetic patients were randomized, in a non-blinded fashion, to an intensive BP-lowering regimen with a target systolic BP goal of <120 mm Hg—with patients on average taking three and a half antihypertensives—or standard BP lowering, where the goal was <140 mm Hg. The primary composite outcome was nonfatal MI, nonfatal stroke, or death from cardiovascular causes, and the mean follow-up was 4.7 years.
After one year, the mean systolic pressure was mm Hg in the intensive-BP-lowering group and mm Hg in the standard group. There was no significant difference in the primary end point between the groups. There was also no difference between the groups in terms of pre-specified secondary end points (except stroke), including the primary outcome plus revascularization or nonfatal heart failure; major coronary disease events; and fatal or nonfatal heart failure.
There was a significant difference in stroke (41% relative risk reduction) between the intensive and standard BP-lowering arms.
Those assigned to the intensive-therapy group were more likely to suffer adverse events due to antihypertensive therapy—3.3% compared with 1.3% in the standard-therapy group (p<0.001).
BP=Blood pressure, CV=Cardiovascular, DM=Diabetes mellitus, HR=Hazard ratio, MI=Myocardial infarction, SBP=Systolic blood pressure
Source: ACCORD study group. NEJM 2010;362:

43. JNC 8: Drug Treatment Thresholds and Goals
Age > 60 yo
Systolic:
Threshold > 150 mmHg
Goal < 150 mmHg
LOE: Grade A
Diastolic:
Threshold > 90 mmHg
Goal < 90 mmHg

44. JNC 8: Drug Treatment Thresholds and Goals
Age < 60 yo
Systolic:
Threshold > 140 mmHg
Goal < 140 mmHg
LOE: Grade E
Diastolic:
Threshold > 90 mmHg
Goal < 90 mmHg
LOE: Grade A for ages 40-59; Grade E for ages 18-39

45. JNC 8: Drug Treatment Thresholds and Goals
Age > 18 yo with CKD or DM
JNC 7: < 130/80 (MDRD NEJM 1994)
Systolic:
Threshold > 140 mmHg
Goal < 140 mmHg
LOE: Grade E
Diastolic:
Threshold > 90 mmHg
Goal < 90 mmHg

46. JNC 8: Hypertension Management Evidence Review
RCT’s December 2009 – August 2013
Major study in hypertension
ACCORD, NEJM 2010
> 2,000 participants
Multicentered
Met all other inclusion/exclusion criteria

47. JNC 8: Initial Drug Choice
Nonblack, including DM
Thiazide diuretic, CCB, ACEI, ARB
LOE: Grade B
Black, including DM
Thiazide diuretic, CCB
LOE: Grade B (Grade C for diabetics)

48. JNC 8: Initial Drug Choice
Age > 18 yo with CKD and HTN (regardless of race or diabetes)
Initial (or add-on) therapy should include an ACEI or ARB to improve kidney outcomes
LOE: Grade B
Blacks w/ or w/o proteinuria
ACEI or ARB as initial therapy (LOE: Grade E)
No evidence for RAS-blockers > 75 yo
Diuretic is an option for initial therapy

49. JNC 8: Subsequent Management
Reassess treatment monthly
Avoid ACEI/ARB combination
Consider 2-drug initial therapy for Stage 2 HTN (> 160/100)
Goal BP not reached with 3 drugs, use drugs from other classes
Consider referral to HTN specialist
LOE: Grade E

50. ACEI/ARB alone or in combination with other drug class
JNC 8
CKD
SBP <140 mmHg DBP <90 mmHg
ACEI/ARB alone or in combination with other drug class
James PA et al. JAMA 2014

51. Dissenting Editorial Ann Intern Med. January 14, 2014
5/17 authors (29%)
“Insufficient evidence” to increase target SBP to 150 mmHg.
Expertise vs. Scientific Evidence

52. Recent HTN Guideline Statements
2013 ESH/ESC Guidelines for the management of arterial hypertension.
J Hypertnsion 2013;31:
An Effective Approach to High Blood Pressure Control: A Science Advisory From the AHA, ACC, and CDC.
Hypertension online November 15, 2013.
Clinical Practice Guidelines for the Management of HTN in the Community A Statements by the ASH/ISH.
J Hypertension 2014;32:3-15

53. Comparison of Recent Guideline Statements
JNC 8
ESH/ESC
AHA/ACC
ASH/ISH
>140/90
Threshold
>140/90 < 60 yr
Eldery SBP >160
>140/90 <80 yr
for Drug Rx
>150/90 >60 yr
Consider SBP
>150/90 > 80 yr
>150/90 >80 yr
if <80 yr
B-blocker No
Yes
First line Rx
Initiate Therapy
>160/100
"Markedly
w/ 2 drugs
elevated BP"

54. Goal BP Group BP Goal (mm Hg) General DM* CKD** JNC 8:
<60 yr: <140/90
< 140/90
>60 yr: <150/90
ESH/ESC:
< 140/85
Elderly
/90
(SBP < 130 if proteinuria)
(<80 yr: SBP<140)
ASH/ISH
>80 yr: <150/90
(Consider < 130/80 if proteinuria)
AHA/ACC
**KDIGO: <140/90 w/o albuminuria
<130/80 if >30 mg/24hr
*ADA: < 140/80 or lower

55. AHA/ACC/CDC Scientific Advisory
Summary/Goals
ESH/ESC 2013
Guidelines
AHA/ACC/CDC Scientific Advisory
JNC 8
ASH/ISH Statement
in general
<140/90
≥ 60 years:
<150/90
< 60 years:
< 140/90
> 80 years
< 150/90
Exception
or special comment
Elderly > 80 years
Elderly < 80 years
Fit elderly
Diabetes
< 140/85
CKD+Proteinuria
< 130/90
Lower targets
African American
LVH
systolic or diastolic LV dysfunction
diabetes
kidney disease
CKD
CKD + Proteinuria
< 130/80

56. Often Combination Therapy will be Required
2013 ESH/ESC Guidelines. J Hypertens 2013

58. SBP ≥ 150 initiate treatment to Target < 150
Pharmacologic Treatment of Hypertension in Adults Aged 60 Years and Older to Higher Versus Lower Blood Pressure Targets: A Clinical Practice Guideline From the ACP and the AAFP 2017
SBP ≥ 150 initiate treatment to Target < 150
Consider Target SBP < 140 if h/o Stroke/TIA
Consider Target SBP < 140 in those with high Cardiovascular Risk

59. Postural Hypotension
Butt DA et al. Arch Intern Med 2013

60. Prevalence of Glycemic Abnormalities
U.S. Population: 309 Million in 2010
Type 1 DM
0.9 Million
Type 2 DM
17.8 Million
Prediabetes
79 Million
It is estimated that more than 80 million people in the United States have diabetes or prediabetes.
Undiagnosed DM
7 Million
104.7 Million
Sources:

61. Prevalence in U.S. Adults
Diabetes Mellitus:
Prevalence in U.S. Adults
Percentage and absolute numbers of diabetics in the United States
Since 1958, the non-institutionalized U.S. population has been sampled annually through interviews of 36,000 to 49,000 randomly selected households. Data from the National Health Interview Survey reveal a steady increase in both the prevalence rate and number of people with a diagnosis of diabetes mellitus. Explanations for this include: an aging U.S. population with higher rates of diabetes at older ages; a reduction in mortality among people with diabetes; and modifications of the criteria used to diagnose diabetes. These explanations may account for some of the increase in the prevalence rate; however, the growing number of overweight and physically inactive individuals likely plays a significant role as well.
Source: Centers for Disease Control and Prevention, Division of Diabetes Translation National Diabetes Surveillance System. Available at

62. 444,649
12.7%

63. Mechanisms by which Diabetes Mellitus Leads to Coronary Heart Disease
Hyperglycemia
Insulin Resistance
HTN Endothelial dysfunction
 AGE
 Oxidative stress
Inflammation
Dyslipidemia
 LDL
 TG
 HDL
 IL-6
 CRP
 SAA
Infection
Thrombosis
 PAI-1
 TF
 tPA
 Defense mechanisms
 Pathogen burden
Subclinical Atherosclerosis
Disease Progression
Infection, inflammation, hyperglycemia, insulin resistance, dyslipidemia, and thrombosis have all been implicated in the development of atherosclerosis and subsequent adverse CV events in patients with diabetes mellitus.
Atherosclerotic Clinical Events
AGE=Advanced glycation end products, CRP=C-reactive protein, CHD=Coronary heart disease HDL=High-density lipoprotein, HTN=Hypertension, IL-6=Interleukin-6, LDL=Low-density lipoprotein, PAI-1=Plasminogen activator inhibitor-1, SAA=Serum amyloid A protein, TF=Tissue factor, TG=Triglycerides, tPA=Tissue plasminogen activator
Source: Biondi-Zoccai GGL et al. JACC 2003;41: 63

64. Adult Treatment Panel III Definition of Metabolic Syndrome
Defined by the presence of >3 risk factors
Risk Factor
Defining Level
Waist circumference (abdominal obesity)
>40 in (>102 cm) in men
>35 in (>88 cm) in women
Triglyceride level
>150 mg/dl
HDL-C level
<40 mg/dl in men
<50 mg/dl in women
Blood pressure
>130/>85 mmHg
Fasting glucose
>110 mg/dl
This slide lists the most recent ATP III criteria for defining metabolic syndrome.
HDL-C=High-density lipoprotein cholesterol
Source: Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:

65. Prevalence in the United States
Metabolic Syndrome:
Prevalence in the United States
National Health and Nutrition Examination Survey (NHANES)
Men
Women
Prevalence, %
This slide shows the prevalence of metabolic syndrome by age as defined by ATP III criteria in NHANES III. While the overall prevalence of metabolic syndrome in the U.S. is about 24%, there is marked variation depending on one’s age. The prevalence of metabolic syndrome is <10% in individuals aged 20–29 years, 20% in individuals aged 40–49 years, and 45% in individuals aged 60–69 years.
20–70+
20–29
30–39
40–49
50–59
60–69
70
Age (Years)
Source: Ford ES et al. JAMA 2002;287:

66. Pre-Diabetic Conditions: Risk of Cardiovascular Disease
Meta-analysis of 18 clinical trials evaluating the risk of CV disease among patients with impaired fasting glucose and/or impaired glucose tolerance
Both types of pre-diabetic conditions increase the risk of CV disease
This meta-analysis of 18 clinical trials sought to evaluate the risk of cardiovascular disease among patients with impaired fasting glucose and/or impaired glucose tolerance. Patients with both types of pre-diabetic conditions were noted to be at increased risk of cardiovascular disease. The RR of CV disease for impaired fasting glucose was 1.20 (95% CI, ) when using a fasting glucose level of mg/dl and 1.18 (95% CI, ) when using a fasting glucose level of mg/dl. The RR of CV disease for impaired glucose tolerance was 1.20 (95% CI, ).
Impaired fasting glucose
Impaired glucose tolerance
CV=Cardiovascular
Source: Ford ES et al. JACC 2010;55:

67. Risk of Cardiovascular Events and Death
Diabetes Mellitus:
Risk of Cardiovascular Events and Death
U.S. adults aged years
***
***
***
***
***
***
***
***
*** * **
This study evaluated the impact of metabolic syndrome on CHD, CVD, and overall mortality among US adults. A total of 6255 subjects 30 to 75 years of age (54% female) from the 2nd National Health and Nutrition Examination Survey were followed for a mean of 13.3 years. Metabolic syndrome was defined by the ATP III criteria. Compared to those with neither metabolic syndrome nor prior CVD, age-, gender-, and risk factor-adjusted hazard ratios (HRs) for CHD mortality were (95% CI, 1.42 to 2.89) for those with metabolic syndrome and 4.19 (95% CI, 3.04 to ) for those with pre-existing CVD. For CVD mortality, HRs were 1.82 (95% CI, to 2.37) and 3.14 (95% CI, 2.49 to 3.96), respectively; for overall mortality, HRs were (95% CI, 1.19 to 1.66) and 1.87 (95% CI, 1.60 to 2.17), respectively.
Overall: In persons with metabolic syndrome but without diabetes, risks of CHD and CVD mortality remained elevated. The presence of diabetes, however, predicted all mortality end points.
*p<.05 compared to none, **p<.01 compared to none, ***p<.0001 compared to none
CHD=Coronary heart disease, CVD=Cardiovascular disease, MetS=Metabolic syndrome
Source: Malik S et al. Circulation 2004;110:

68. National Health and Nutrition Examination Survey (NHANES)
Metabolic Syndrome:
Risk of Coronary Heart Disease*
National Health and Nutrition Examination Survey (NHANES)
19.2%
13.9%
CHD Prevalence
8.7%
7.5%
Metabolic syndrome is associated with an increased prevalence of coronary heart disease. Among individuals with metabolic syndrome and diabetes mellitus, the prevalence of coronary heart disease is even greater.
No MS/No DM
MS/No DM
DM/No MS
DM/MS
54%
29% 2%
15%
% of Population
*Among individual >50 years
CHD=Coronary heart disease, DM=Diabetes mellitus, MS=Metabolic syndrome
Source: Alexander CM et al. Diabetes 2003;52:

69. Risk of Cardiovascular Events and Death
Diabetes Mellitus:
Risk of Cardiovascular Events and Death
Meta-analysis of 102 clinical trials evaluating the risk of cardiovascular events due to diabetes mellitus
Diabetes mellitus significantly increases the risk of adverse CV events
CV=Cardiovascular
Source: Emerging Risk Factors Collaboration. Lancet 2010;375:

70. Impact of Glycemic Control on CV Risk
Diabetes Mellitus:
Impact of Glycemic Control on CV Risk
United Kingdom Prospective Diabetes Study (UKPDS) 35 10 20 30 40 50 60
Myocardial Infarction
Microvascular Disease
5.5%
6.5%
7.5%
8.5%
9.5%
10.5%
HbA1C%
There is an increase in the risk of both macrovascular and microvascular complications as hemoglobin A1C levels rise.
The risk of CV disease increases with increasing HbA1C
CV=Cardiovascular, HbA1C=Glycosylated hemoglobin
Stratton IM et al. BMJ 2000;321:

71. Diabetes Mellitus (Type II): Effect of Intensive Glycemic Control
United Kingdom Prospective Diabetes Study (UKPDS)
3,867 patients with DM randomized to intensive therapy with a sulphonylurea or insulin (mean HbA1C 7.0%) or conventional therapy (mean HbA1C 7.9%)
P=0.03
P=0.05
% relative risk reduction
P=0.02
P<0.01
P<0.01
The UK Prospective Diabetes Study (UKPDS) Group randomized 3,867 newly diagnosed patients with type 2 diabetes to intensive treatment with a sulphonylurea or insulin vs. conventional treatment with dietary modification. Over 10 years of follow-up, the hemoglobin A1c was 7.0% ( %) in the intensive group compared with 7.9% ( %) in the conventional group. In the intensive treatment group, the relative risk was 6% lower (non-significant) for all-cause mortality (p=0.44), 12% lower for any diabetes-related endpoint (p=0.029), and 25% lower for microvascular endpoints (p=0.0099).
Intensive glycemic control in DM reduces the risk of
microvascular complications
DM=Diabetes mellitus, HbA1C=Glycosylated hemoglobin
Source: UKPDS Group. Lancet 1998;352: 71

72. Effect of Blood Pressure Control
Diabetes Mellitus:
Effect of Blood Pressure Control
United Kingdom Prospective Diabetes Study (UKPDS)
In the United Kingdom Prospective Diabetes Study (UKPDS), tight blood pressure control was associated with greater CV risk reduction compared to tight glycemic control.
BP control yields greater CV risk reduction than glycemic control
*P=0.04, †P=0.029, ‡P=0.04 vs less tight BP control (<180/105 mm Hg)
BP=Blood pressure, CV=Cardiovascular, MI=Myocardial infarction
Sources:
UKPDS 38. BMJ 1998;317:
UKPDS 33. Lancet 1998;352:

73. Diabetes Mellitus (Type II): Effect of Intensive Glycemic Control
United Kingdom Prospective Diabetes Study (UKPDS)
10-Year Follow-Up
Sulphonylurea vs. Conventional Therapy
Insulin vs. Conventional Therapy
In a 10-year follow-up of the United Kingdom Prospective Diabetes Study (UKPDS), long-term risk of a myocardial infarction was reduced with intensive glycemic control in diabetic patients.
Intensive glycemic control in DM reduces the long-term risk of MI
DM=Diabetes mellitus, MI=Myocardial infarction
Source: Holman RR et al. NEJM 2008;359:

74. Diabetes Mellitus (Type II): Effect of Intensive Glycemic Control
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial
10,251 diabetic patients randomized to intensive glucose lowering (HbA1C <6%) or standard glucose lowering (HbA1C %) for 3.5 years
Intensive glucose lowering does not reduce adverse CV events and
increases all-cause mortality
P=0.16 9 9
P=0.04
7.2
6.9 6 6
5.0
CV death, MI, or stroke (%)
All-cause mortality (%)
4.0 3 3
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial sought to evaluate whether intensive glucose lowering with a target HbA1C <6.0% would reduce the rate of cardiovascular events as compared to standard glucose lowering with a target HbA1C of % in 10,251 diabetic patients. The trial was stopped early after a mean of 3.5 years due to increased mortality in the intensive glucose lowering group (p=0.04). Cardiovascular event rates were similar in the intensive glucose lowering and standard therapy groups (p=0.16).
Standard Therapy
Intensive Glucose Lowering
Standard Therapy
Intensive Glucose Lowering
CV=Cardiovascular, HbA1C=Glycosylated hemoglobin, MI=Myocardial infarction
Source: ACCORD Study Group. NEJM 2008;358;

75. Effect of Intensive Risk Factor Modification
Diabetes Mellitus:
Effect of Intensive Risk Factor Modification
STENO-2 Study
160 patients with type 2 DM randomized to targeted intensive multifactorial intervention† or conventional treatment of CV risk factors for 8 years
Intensive risk factor modification reduces CV events in DM 60
Intensive Therapy†
Conventional Therapy 40
Primary Endpoint* (%) 20
HR=0.47, P=0.008 12 24 36 48 60 72 84 96
Months of Follow-Up
The STENO-2 Study randomized 160 patients (mean age of 55 years) with type 2 diabetes and microalbuminuria to targeted intensive multifactorial intervention or conventional treatment of cardiovascular risk factors for 8 years. The targeted intervention involved pharmacologic therapy and behavior modification targeting dyslipidemia, hyperglycemia, hypertension, microalbuminuria, and secondary prevention of cardiovascular disease with aspirin. The primary end point was a composite of nonfatal MI, cardiovascular death, revascularization, nonfatal stroke, and amputation. The hazard ratio for the primary end point in the intensive group was 0.47 (95% CI, 0.22 to 0.74; P=0.01).
*Death from CV causes, nonfatal MI, Coronary artery bypass graft surgery, percutaneous coronary intervention, nonfatal stroke, amputation, or surgery for PAD
†Aggressive treatment of dyslipidemia, hyperglycemia, hypertension, microalbuminuria, and secondary prevention of CV disease
CV=Cardiovascular, DM=Diabetes mellitus MI=Myocardial infarction, PAD=Peripheral artery disease
Gaede P et al. NEJM 2003;348: 75

76. EMPA-REG OUTCOME: Primary Endpoint -- 3-Point MACE*
All patients had established CV disease 75 % CAD, 15% Latinos, recent MI 46%, CHF 10% A1-C 8%
SGLT-2 inhibitor: Selective sodium-glucose transporter-2 inhibitor
Proximal renal tubule
Increase urinary glucose excretion
Jardiance 10 or 25 mg
Indicated to reduce the risk of cardiovascular death in adults with type 2 DM and CV disease
GFR >30

77. Effect of Empagliflozin on HF Outcomes in Subgroups by Age: Results From EMPA-REG OUTCOME

78. LEADER: Study Design GLP-1 Agonist
Glucagon-like Peptide-1 Agonist (Victoza, Saxenda)

79. LEADER: Primary Outcome*
9,340 patients median f/u 3.8 yrs
Primary Endpoint 13.0% in Liraglutide vs % placebo
Fewer CV deaths and all deaths, non-significantly lower MI, or Stroke
Daily sc inj

80. Effect of Blood Pressure Control
Diabetes Mellitus:
Effect of Blood Pressure Control
Hypertension Optimal Treatment (HOT) Study
18,790 patients with a baseline diastolic BP of mm Hg randomized to a target diastolic BP of <90 mm Hg, <85 mm Hg, or <80 mm Hg
There is greater benefit with more intensive BP control in diabetics
Major CV events per
1000 patient-years
Patients with
Diabetes
Patients without
Diabetes
The importance of reducing diastolic BP in patients with diabetes mellitus was demonstrated in the Hypertension Optimal Treatment (HOT) trial. In the HOT trial, 18,790 patients with hypertension and a diastolic BP between 100 and 115 mm Hg were randomized to 1 of 3 target diastolic BP groups: 90 mm Hg, 85 mm Hg, or 80 mm Hg. A subgroup of 1501 patients had DM at baseline. A 5-step treatment regimen that started with felodipine was used to lower BP. At the study end, 78% of patients were still taking felodipine, usually with an angiotensin converting enzyme inhibitor (41%) or a -blocker (28%).
The incidence of major CV events (MI, stroke, CV mortality) did not differ significantly among the 3 target BP groups in patients who did not have diabetes. Events per 1000 patient-years were 9.9, 10.0, and 9.3 for the 90 mm Hg, 85 mm Hg, or 80 mm Hg groups, respectively. In patients with diabetes mellitus, however, there was a 51% reduction in major CV events in the target group 80 mm compared with target group 90 mm (P for trend = .005). Events per 1000 patient-years were 24.4, 18.6, and 11.9 (P=0.005 for trend) for those with diabetes in the 90 mm Hg, 85 mm Hg, or 80 mm Hg groups, respectively.
Diastolic BP goal
Diastolic BP goal
BP=Blood pressure, CV=Cardiovascular
Source: Hansson L et al. Lancet 1998;351:

81. ADA Smoking Cessation Recommendations
for Patients with Diabetes Mellitus
Primary Prevention
All patients should be advised not to smoke.
Smoking cessation counseling and other forms of treatment should be included as a routine component of diabetes care.
ADA=American Diabetes Association
Source: American Diabetes Association. Diabetes Care 2010;33:S11-61

82. Most Preventable Cause of Death
Tobacco Use:
Most Preventable Cause of Death
Most preventable causes of death in the U.S. in 1990 and 2000
Causes
# (%) in 1990
# (%) in 2000
Tobacco
400,000 (19)
435,000 (18)
Poor diet and physical activity (obesity)
300,000 (14)
400,000 (17)
Alcohol consumption
100,000 (5)
85,000 (4)
Microbial agents
90,000 (4)
75,000 (3)
Toxic agents
60,000 (3)
55,000 (2)
Motor vehicle accidents
25,000 (1)
43,000 (2)
Firearms
35,000 (2)
29,000 (1)
Sexual behavior
30,000 (1)
20,000 (<1)
Illicit drug use
17,000 (<1)
Total
1,060,000 (50*)
1,159,000 (48%*)
Tobacco abuse remains the most common preventable cause of death in the United States.
*Reflects percent total of 9 most preventable causes of death
Source: Mokdad AH et al. JAMA 2004;291: 82

83. Cigarette Smoking Cessation Evidence:
Risk of Non-fatal Myocardial Infarction*
Study
RR (95% Cl)
Aberg, et al. 1983
0.67 ( )
Herlitz, et al. 1995
0.99 ( )
Johansson, et al. 1985
( )
Perkins, et al. 1985
3.87 ( )
Sato, et al. 1992
0.10 ( )
Sparrow, et al. 1978
0.76 ( )
Vlietstra, et al. 1986
0.63 ( )
A meta-analysis of 20 prospective cohort studies demonstrated a 36% crude relative risk reduction in mortality for CHD patients among individuals that quit smoking as compared to those that continued to smoke (RR 0.64; 95% confidence interval [CI], ). Among the 8 studies that included data on nonfatal reinfarction, the pooled relative risk for nonfatal MI was 0.68 (95% CI, ).
Voors, et al. 1996
0.54 ( )
0.1
1.0 10
Ceased smoking
Continued smoking
*Includes those with known coronary heart disease
Source: Critchley JA et al. JAMA 2003;290:86-97 83

84. AHA Primary Prevention of CV Disease in DM Tobacco Recommendations
All patients should be asked about tobacco use status at every visit.
Every tobacco user should be advised to quit.
The tobacco user’s willingness to quit should be assessed.
The patient can be assisted by counseling and by developing a plan to quit.
Follow-up, referral to special programs, or pharmacotherapy (e.g., NRT and buproprion) should be incorporated as needed.
AHA=American Heart Association, CV=Cardiovascular,
DM=Diabetes mellitus, NRT=Nicotine replacement therapy
Source: Buse JB et al. Circulation 2007;115:

85. Smoking Cessation
Cessation of cigarette smoking constitutes the single most important preventive measure for CAD.

86. Adverse Effects of Physical Inactivity
Inflammation
Dyslipidemia
Age
Hypertension
Diabetes Mellitus
Smoking
Physical inactivity directly and indirectly increases the risk of coronary heart disease by multiple distinct and interrelated mechanisms.
Obesity
Hypercoagulability
Atherosclerosis
Genetics
Novel Risk Factors 86

87. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults
Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, American Pharmacists Association, American Society for Preventive Cardiology, Association of Black Cardiologists, Preventive Cardiovascular Nurses Association, and WomenHeart: The National Coalition for Women with Heart Disease
© American College of Cardiology Foundation and American Heart Association, Inc.

88. 4 Statin Benefit Groups Clinical ASCVD*
LDL-C ≥190 mg/dL, Age ≥21 years
Primary prevention – Diabetes: Age years, LDL-C mg/dL
Primary prevention - No Diabetes†: ≥7.5%‡ 10-year ASCVD risk, Age years, LDL-C mg/dL
*Atherosclerotic cardiovascular disease
†Requires risk discussion between clinician and patient before statin initiation
‡Statin therapy may be considered if risk decision is uncertain after use of ASCVD risk calculator

89. Coronary Heart Disease Risk According to LDL-C Level
3.7
2.9
2.2
1.7
1.3
1.0
Relative Risk for Coronary Heart Disease (Log Scale)
This graph demonstrates the relative risk for coronary heart disease relative to the LDL-C level.
LDL-Cholesterol (mg/dL)
CHD=Coronary heart disease, LDL-C=Low-density lipoprotein cholesterol
Source: Grundy S et al. Circulation 2004;110: 89

90. Attributable Risk Factors for a First Myocardial Infarction
INTERHEART Study
100 90 80 60 50
PAR (%) 40 36 33 20 18 20 14 12 10 7
In this study of 15,152 patients, lipids had the highest population attributable risk for a first myocardial infarction among 9 risk factors for cardiovascular disease.
Smoking
Fruits/ Veg
Exercise
Alcohol
Hyper- tension
Diabetes
Abdominal
obesity
Psycho- social
Lipids
All 9 risk factors
Lifestyle factors
n=15,152 patients and 14,820 controls in 52 countries
MI=Myocardial infarction, PAR=Population attributable risk (adjusted for all risk factors)
Source: Yusuf S et al. Lancet. 2004;364:

91. HMG-CoA Reductase Inhibitor Evidence:
Primary Prevention
Relationship between LDL-C levels and event rates in select primary prevention statin trials 10
Statin 8
Placebo
WOSCOPS
WOSCOPS 6
AFCAPS
CHD event rate (%)
AFCAPS 4
ASCOT 2
ASCOT
Data from the main primary prevention trials (prior to publication of the MEGA and JUPITER trials) are displayed here.
P=0.0019 –1 55 75 95
115
135
155
175
195
LDL cholesterol (mg/dL)
AFCAPS= Air Force/Texas Coronary Atherosclerosis Prevention Study, ASCOT= Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm, LDL-C=Low density lipoprotein cholesterol, WOSCOPS= West of Scotland Coronary Prevention Study
Source: O’Keefe JH Jr et al. JACC 2004;43:

92. HMG-CoA Reductase Inhibitor Evidence:
Secondary Prevention
Relationship between LDL-C levels and event rates in secondary prevention statin trials of patients with stable CHD 30 4S
Statin
Placebo 25 4S 20
Event (%)
LIPID
LIPID 15
CARE
CARE
HPS 10
HPS
TNT (atorvastatin 10 mg/d) 5
TNT (atorvastatin 80 mg/d)
Data from the main secondary prevention trials (prior to publication of the IDEAL trial) are displayed here. The lowering of LDL-C levels with statin therapy leads to a reduction in cardiovascular morbidity and mortality, at multiple baseline risk levels. 70 90
110
130
150
170
190
210
LDL-C (mg/dL)
CARE=Cholesterol and Recurrent Events Trial, CHD=Coronary heart disease, HPS=Heart Protection Study, LDL-C=Low density lipoprotein cholesterol, LIPID=Long-term Intervention with Pravastatin in Ischaemic Disease, 4S=Simvastatin Survival Study, TNT=Treating to New Targets
Source: LaRosa JC et al. NEJM 2005;352: 92

93. Primary Prevention Global Risk Assessment
To estimate 10-year ASCVD* risk
New Pooled Cohort Risk Equations
White and black men and women
More accurately identifies higher risk individuals for statin therapy
Focuses statin therapy on those most likely to benefit
You may wish to avoid initiating statin therapy in high-risk groups found not to benefit (higher grades of heart failure and hemodialysis)
*10-year ASVD: Risk of first nonfatal myocardial infarction, coronary heart disease death, nonfatal or fatal stroke

94. Framingham Risk Score On Line Calculator
Risk Stratification:
Framingham Risk Score On Line Calculator
Source: Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Risk Assessment Tool.

95. ASCVD Risk Estimator Gender Age Race Total Cholesterol HDL-Cholesterol
White
African American
Other
Total Cholesterol
HDL-Cholesterol
Systolic BP
Treatment of Hypertension
Diabetes
Smoker

96. Primary Prevention Statin Therapy
Thresholds for initiating statin therapy derived from 3 exclusively primary prevention RCTs
Before initiating statin therapy, clinicians and patients engage in a discussion of the potential for ASCVD risk reduction benefits, potential for adverse effects, drug-drug interactions, and patient preferences

97. Summary of Statin Initiation Recommendations to Reduce ASCVD Risk (Revised Figure)

98. Summary of Statin Initiation Recommendations to Reduce ASCVD Risk (Revised Figure)
*The Pooled Cohort Equations can be used to estimate 10-year ASCVD risk in individuals with and without diabetes. A downloadable spreadsheet enabling estimation of 10-year and lifetime risk for ASCVD and a web-based calculator are available at and The calculator should be used to inform decision making in primary prevention patients not on a statin.
†Consider moderate-intensity statin as more appropriate in low-risk individuals.
‡For those in whom a risk assessment is uncertain, factors such as primary LDL–C >160 mg/dL or other evidence of genetic hyperlipidemias, family history of premature ASCVD with onset <55 years of age in a first degree male relative or <65 years of age in a first degree female relative, lifetime risk of ASCVD, CAC score ≥300 Agatston units, or ≥75 percentile for age, sex, and ethnicity (For additional information, see ABI <0.9, or hs-CRP >2 mg/L. Additional factors that may aid in individual risk assessment may be identified in the future.
§1) Potential ASCVD risk reduction benefits (e.g., absolute risk reduction from moderate- or high-intensity statin therapy can be approximated by using the estimated 10-year ASCVD risk and the relative risk reduction of ~30% for moderate-intensity statin or ~45% for high-intensity statin therapy. 2) Potential adverse effects. The excess risk of diabetes is the main consideration in ~0.1 excess case per 100 individuals treated with a moderate-intensity statin for 1 year and ~0.3 excess cases per 100 individuals treated with a high-intensity statin treated patients for 1 year. Note: a case of diabetes is not considered equivalent to a fatal or nonfatal MI or stroke. Both statin-treated and placebo-treated participants experienced the same rate of muscle symptoms. The actual rate of statin-related muscle symptoms in the clinical population is unclear. Muscle symptoms attributed to statin should be evaluated in as Table 8, Safety Rec 8.

99. Clinical ASCVD: Initiating Statin Therapy
*Fasting lipid panel preferred. In a nonfasting individual, a nonfasting non-HDL–C ≥220 mg/dL may indicate genetic hypercholesterolemia that requires further evaluation or a secondary etiology. If nonfasting triglycerides are ≥500 mg/dL, a fasting lipid panel is required.
†It is reasonable to evaluate the potential for ASCVD benefits and for adverse effects, and to consider patient preferences, in initiating or continuing a moderate- or high-intensity statin, in individuals with ASCVD >75 years of age.

100. Intensity of Statin Therapy
*Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice. There might be a biologic basis for a less-than-average response.
†Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in IDEAL (Pedersen et al).
‡Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA due to the increased risk of myopathy, including rhabdomyolysis.

101. Individuals Not in a Statin Benefit Group
In those for whom a risk decision is uncertain, these factors may inform clinical decision making:
Family history of premature ASCVD
Elevated lifetime risk of ASCVD
LDL-C ≥160 mg/dL
hs-CRP ≥2.0 mg/L
CAC score ≥300 Agaston units
ABI <0.9
Statin use still requires discussion between clinician and patient

102. Aspirin Evidence: Primary Prevention
Physician’s Health Study (PHS)
22,071 male participants randomized to aspirin (325 mg every other day) followed for an average of 5 years
Aspirin reduces the risk of myocardial Infarction among men
The Physicians' Health Study was a randomized, double-blind, placebo-controlled primary prevention trial designed to determine whether aspirin (325 mg every other day) was associated with a reduction in cardiovascular disease mortality. The trial included 22,071 participants, with an average follow-up of 60 months.
Aspirin use was associated with a 44% reduction in the risk of MI; however, this effect was mainly present in men >50 years of age and no reduction in total cardiovascular mortality (RR 0.96; 95% CI 0.60 to 1.54) was observed. A slightly increased risk of stroke was observed among those taking aspirin (p=NS). This trend was noted primarily in the subgroup with hemorrhagic stroke (RR 2.14; 95% CI [0.96 to 4.77]; p=0.06). There was a non-significant increased risk of gastrointestinal ulcers in the aspirin group (RR 1.22, CI [0.98 to 1.53]; p=0.08).
Overall: In men (especially >50 years of age), aspirin is associated with a reduced risk of a first MI.
CI=Confidence interval, CV=Cardiovascular
Source: Steering Committee of the Physicians’ Health Study Research Group. NEJM 1989;321:
102

103. Aspirin Evidence: Primary Prevention
Womens’ Health Study (WHS)
39,876 women randomized to aspirin (100 mg every other day) or placebo for an average of 10 years
Aspirin does not reduce cardiovascular events among women
The Women's Health Study was a double-blind, placebo-controlled trial that randomized 39,876 healthy women >45 years of age to low dose aspirin (100 mg every other day) versus placebo for a mean follow up of 10 years. There was no reduction in the primary composite endpoint of nonfatal MI, nonfatal stroke, or death from a cardiovascular cause. Aspirin use was associated with a 17% reduction in the risk of stroke (RR 0.83; ; P=0.04), a 24% reduction in the risk of ischemic stroke (RR 0.76; ; P=0.009), and a non-significant increase in the risk of hemorrhagic stroke (RR 1.24; ; P=0.31). Aspirin had no effect on the risk of fatal or nonfatal myocardial infarction (RR 1.02; ; P=0.83).
Among women >65 years of age, aspirin use was associated with a reduction of major cardiovascular events (RR 0.74; ; P=0.008) and risk of ischemic stroke (RR 0.70; ; P=0.05). GI bleeding requiring transfusion was more frequent in the aspirin group (RR 1.40; ; P=0.02).
Overall: The routine use of aspirin in low risk women (<10% 10 year risk of a CHD event) is not recommended. Aspirin use in women >65 can reduce the risk of cardiovascular events.
Source: Ridker P et al. NEJM 2005;352:
103

104. Aspirin reduces the risk of stroke in women and MI in men
Aspirin Evidence:
Primary Prevention
Sex-specific meta-analysis of 51,342 women and 44,114 men randomized to aspirin (doses ranging between 100 mg every other day to 500 mg daily) vs. placebo for years
Aspirin reduces the risk of stroke in women and MI in men *
Odds ratio
* p<0.05
Data from six studies were included in this meta-analysis: The Physicians' Health Study (1989), the Women's Health Study (2005), the Primary Prevention Project (2001), the Thrombosis Prevention Trial (1998), the Hypertension Optimal Treatment (HOT) trial (1998), and the British Doctor's Trial (1988).
Among 51,342 women, there were 1285 major cardiovascular events: 625 strokes, 469 MIs, and 364 cardiovascular deaths. Aspirin therapy was associated with a significant 12% reduction in cardiovascular events (odds ratio [OR], 0.88; 95% confidence interval [CI], ; P = .03) and a 17% reduction in stroke (OR, 0.83; 95% CI, ; P = .02), predominantly resulting from reduced rates of ischemic stroke (OR, 0.76; 95% CI, ; P = .008). There was no significant effect on MI or cardiovascular mortality.
Among 44,114 men, there were 2047 major cardiovascular events: 597 strokes, 1023 MIs, and 776 cardiovascular deaths. Aspirin therapy was associated with a significant 14% reduction in cardiovascular events (OR, 0.86; 95% CI, ; P = .01) and a 32% reduction in MI (OR, 0.68; 95% CI, ; P = .001). There was no significant effect on stroke or cardiovascular mortality.
Aspirin treatment increased the risk of bleeding in women (OR, 1.68; 95% CI, ; P = .01) and men (OR, 1.72; 95% CI, ; P<.001) alike.
AC=All cause, CV=Cardiovascular, MCE=Major cardiovascular events, MI=Myocardial infarction
Source: Berger JS et al. JAMA. 2006;295:
104

105. Aspirin Evidence: Primary Prevention
Antithrombotic Trialists’ (ATT) Collaboration
Rate Ratios for Vascular Events
P-value
Non-fatal MI
P<0.0001
Any stroke
P=0.40
Vascular Mortality
P=0.70
Major extracranial bleed
P<0.0001
Serious Vascular Events
P=0.0001
This data was taken from a meta-analysis of 6 randomized trials of antiplatelet therapy for prevention of death, MI, and stroke in low risk patients. In the primary prevention trials the absolute risk of a serious vascular event was an order of magnitude less than in the secondary prevention trials, and the absolute reduction in occlusive events only about twice as large as the absolute increase in bleeding. Moreover, these trials of aspirin were mainly in people who were not taking statin therapy, which would have reduced both MI and stroke rates with little hazard.
Overall: Aspirin is of uncertain net value for the primary prevention of CVD.
0.5
1.0
1.5
2.0
Antiplatelet Better
Antiplatelet Worse
Aspirin reduces the risk of MI and vascular events at the expense of bleeding
Source: Antithrombotic Trialists’ Collaboration. Lancet 2009;373:

106. Preguntas ?

107. Preguntas Pre y Post Prueba
En relación a las Guías del AHA/ACC 2013 para el Tratamiento de Colesterol en Adultos; cual de las siguientes aseveraciones es Falsa:
Al igual que en las Guías anteriores se recomiendan niveles específicos de LDL como meta de tratamiento dependiendo del riesgo.
Se enfatiza el uso de Estatinas en grupos de pacientes a riesgo para prevención primaria y prevención secundaria.
Se recomienda calcular el riesgo de desarrollar Enfermedad Ateroesclerótica Cardiovascular a 10 años en pacientes que No han tenido eventos cardiovasculares como Infarto al Miocardio o Infarto Cerebral.
El panel de expertos No hace recomendaciones para el uso de Estatinas en pacientes de Fallo Cardiaco Sistólico Isquémico Clase II a IV o pacientes en Hemodiálisis.

108. Preguntas Pre y Post Prueba
2. La Asociación Americana del Corazón, contrario al mas reciente JNC-8 del 2014, recomienda tratamiento para hipertensión:
≥ 140/90 hasta la edad de 80 años y ≥ 150/90 después de los 80.
Cierto
Falso