Interview with: Peter Sheehan, MD, President, Sheehan Health Management Consulting, LLC, New York, NY

Definition of risk Although many clinicians have

become familiar with the term “metabolic syndrome,” the definition does not adequately encapsulate the various factors that contribute to risk for cardiovascular disease (CVD).

Therefore, the American Diabetes Association (ADA) promotes using the term “cardiometabolic risk.”

Metabolic syndrome - A person is considered to have the metabolic syndrome if he or she has ³3 of the following risk factors:  Weight Abnormally high

Elevated Blood Pressure Insulin Resistance   Glucose Intolerance     HDL Elevation Triglyceride Elevation

WEIGHT

Additional cardio-metabolic risk factors Nonmodifiable Modifiable

AgeRaceSex  Family history

   Inflammation   Hypercoagulation

   Smoking status

Physical inactivity

Gestational diabetes (GDM)

Women with histories of GDM Have increased risk of developing overt

type 2 diabetes, ALSO are at increased risk of

developing CVD. Children of these women also have

elevated risk of developing metabolic abnormalities e.g, central obesity; high levels of triglycerides, at a young age.

Risk factor management - Focus

smoking cessation lipid controlblood pressure (BP) control

glycemic controlantiplatelet therapy

Smoking cessation:

A variety of pharmacologic agents are available (eg, varenicline; nicotine replacement therapy) and help improve quit rates.

LDL-cholesterol: Therapy — primarily statin therapy.

Targets — low-density lipoprotein (LDL) cholesterol <100 mg/dL for individuals with ³2 cardio-metabolic risk factors;

LDL cholesterol <70 mg/dL for those with diabetes and established CVD.

Apolipoprotein B (Apo B):

Measurement provides an indication of the number of atherogenic lipid particles, because it occurs in a one-to-one ratio with LDL and very-low density lipoprotein (VLDL) choles terol.

Targets — <80 mg/dL for patients with high cardiometabolic risk; <90 mg/dL for those at moderate risk. Implications — LDL particles are not uniform in size or density.

For a given level of LDL cholesterol, a high density of particles (ie, small, dense particles) is associated with a high degree of atherogenicity,

whereas a low density of particles (ie, large, “fluffy” particles) is associated with a low degree of atherogenicity.

Non–HDL-cholesterol: Total cholesterol minus HDL-cholesterol seems to be more closely correlated with risk for CVD than is LDL-cholesterol.

Prioritizing management approaches to reduce cardiometabolic risk •   Primary: Physical activity (eg, 30 min/day of walking) and dietary interventions are critical components in the management of cardio-metabolic risk — especially in patients who are overweight or obese and have multiple risk factors.

In patients with type 2 diabetes, weight loss may have a greater impact on car diometabolic risk than does glycemic control.

Prioritizing management approaches to reduce cardiometabolic risk Secondary: BP control; lipid control;

smoking cessation. Tertiary: Glycemic control (Although

glycemic control is strongly correlated with microvascular complications, its impact on cardiometabolic risk is relatively small, compared to the risk conferred by hyper tension, dyslipidemia, and smoking.)

Interview with:

Robert Eckel, MD, Professor of Medicine and Charles A. Boettcher II Chair in Atherosclerosis, University of Colorado Health Sciences Center, Denver, CO

Women HDL-cholesterol:

In premenopausal women, levels are generally higher than in men, contributing to lower risk for CVD.

Hypertension: Somewhat lower prevalence, compared to men.

Diabetes: Women with diabetes have the same risk for CVD as do men with diabetes (ie, the “gender benefit” seems to disappear).

Women

Women-Role of estrogen

The lower risk for CVD in premenopausal women has been attributed to estrogen, but the relationship may be more complex.

Before puberty, girls and boys have similar levels of HDL-cho lesterol, but those levels decrease after puberty (with the onset of increased androgen production) in boys.

After menopause, not only do estrogen levels decrease, but the relative concentration of androgens increases.

Race/ethnicity - Hypertension: Higher prevalence among blacks.

HDL-cholesterol: Latinos tend to have lower levels than whites, who tend to have somewhat lower levels than blacks.

Management: In general, targets (eg, BP, lipids, blood glucose) are the same, regardless of race/ethnicity.

Interview with:Jeffrey Curtis, MD, Coinvestigator, Action for Health in Diabetes (Look AHEAD) Trial;

National Institute of Dia betes and Digestive and Kidney Diseases (NIDDK), Phoenix, AZResults from baseline

stress testing Patients reported no symptoms of CVD 22.5% of tests showed abnormal results.• 12% of participants were unable to achieve ³5

METs    ST segment depression was seen in 7.6%. 0.5% of participants demonstrated abnormal

recovery of heart rate  Angina occurred in 1.1%. Detectable arrhythmia occurred in 0.71%. The variable that best predicted abnormal

results was age.

Conclusions from the Study

Diabetes Interview with:Trevor Orchard, MBBCh, MMedSci, FAHA, Professor of Epidemiology, Pediatrics, and Medicine, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA

Predictors of Future Development of Arterial Stiffness :

Measurements

Cardiac autonomic nerve function: Heart rate variability (R-R interval)

during deep breathing, expressed as the expiration-to-inspiration (E/I) ratio.

Arterial stiffness: Pulse wave analysis was measured using

a SphygmoCor Px system. Pulse pressure is another useful measure,

but data by Prince and colleagues show that augmentation pressure and sub-endocardial viability ratio (SEVR) are somewhat better predictors.

Reducing cardio-metabolic risk Pharmacogenetics:

Risk for CVD is reduced with vitamin E therapy in individuals with type 2 diabetes who have the haptoglobin 2-2 genotype.

Emerging data also suggest a relationship between haptoglobin genotype and risk for CVD in patients with type 1 diabetes.

Management of standard risk factorsVery important to control BP and lipids.

For example, statin therapy should be considered for all patients with type 1 diabetes who are 30 yr of age.

Risk assessment — Individuals with type 1 diabetes should be evaluated for cardio-metabolic risk on a regular basis, beginning at puberty.

Targets — smoking cessation; LDL cholesterol 100 mg/dL; BP 120/80 mm Hg **.*