SAN DIEGO—Metabolic syndrome poses a considerable health threat as it nearly doubles the risk of stroke, is significantly associated with carotid artery stiffness, and is a potent stroke risk factor for minorities, researchers reported at the American Stroke Association’s 29th International Stroke Conference.

“Metabolic syndrome is a major health hazard—particularly in women and minorities—but we’ve known very little about its relationship to stroke,” said Edgar J. Kenton, III, MD, Professor of Clinical Neurology at Thomas Jefferson University in Philadelphia. Dr. Kenton served as moderator on a panel discussion of metabolic syndrome and its impact on stroke.

According to the US National Cholesterol Education Program and the World Health Organization, metabolic syndrome is defined as the simultaneous presence of at least three of five metabolic abnormalities:
• abdominal obesity (waist circumference greater than 35 inches in women and greater than 40 inches in men)
• high fasting levels of blood sugar (fasting blood glucose of 110 to 126 mg/dL)
• high triglycerides levels (150 mg/dL or greater)
• low levels of HDL (less than 40 mg/dL in men and less than 50 mg/dL in women)
• high blood pressure (130/85 mm Hg or greater, or current treatment with antihypertensive medication)

METABOLIC SYNDROME COMPARED WITH DIABETES AS A RISK FACTOR FOR STROKE

“Before it becomes necessary to begin aggressive treatment of diabetes and other predisposing factors for stroke, it might be possible to take steps that can prevent these serious conditions from developing,” said Robert M. Najarian, lead author of one study and third-year medical student at Boston University School of Medicine.

His team found that compared with controls, men with metabolic syndrome have a 78% greater risk of stroke, and women with the syndrome have more than double the stroke risk than those who do not have the syndrome. But the overall stroke risk associated with metabolic syndrome remained below the stroke risk associated with diabetes.

Metabolic syndrome greatly increases a person’s chances of developing type 2 diabetes mellitus; because of its strong association with diabetes, it is often considered a prediabetic condition. Both conditions increase the risk of coronary heart disease, and diabetes is a potent risk factor for stroke. However, the relative effect of metabolic syndrome and diabetes on stroke risk has not been studied extensively, explained Mr. Najarian. His team’s findings suggest that treating the risk-factor components of metabolic syndrome might reduce stroke risk before the onset of type 2 diabetes mellitus.

Mr. Najarian and his coinvestigators compared the impact of metabolic syndrome and diabetes on the 10-year risk of stroke and transient ischemic attack (TIA). The study involved 1,881 participants without diabetes (average age, 59) of the offspring cohort in the Framingham Heart Study. Men and women were evaluated for diabetes and were considered to have metabolic syndrome if they met at least three of the five criteria.

The investigators found that 27.6% of the nondiabetic men and 21.5% of the nondiabetic women met the criteria for a diagnosis of metabolic syndrome without including diabetes. When an additional 216 participants with diabetes were included in the analysis, 30.3% of men and 24.7% of women met the diagnostic criteria for metabolic syndrome.

During a maximum follow-up of 14 years, 5.6% of the men in the study and 4.3% of the women had a stroke or TIA. Patients with diabetes had a significantly higher 10-year risk of stroke compared with people with metabolic syndrome: 14% versus 8% in men and 10% versus 6% in women.

PREVENTION BEFORE AGGRESSION

Although metabolic syndrome is a less potent risk factor for stroke than diabetes, the condition is more prevalent than diabetes, making it a major consideration for stroke risk, Mr. Najarian said. Interventions aimed at preventing or treating metabolic syndrome could have a major impact on overall stroke risk.

“Metabolic syndrome looks like the precursor for a number of health problems,” Mr. Najarian observed. “Because the prevalence of the syndrome is so high, we need to start thinking about how to prevent the condition, particularly since it appears to be a factor in the continuum that leads to outright diabetes and cardiovascular disease. The end result is a higher death rate from all causes, a higher death rate from vascular causes, and higher rates of cardiovascular disease.”

METABOLIC SYNDROME AND CAROTID ARTERY STIFFNESS

Because carotid artery stiffness is believed to be a marker for cardiovascular disease—and therefore also may be an indicator of stroke risk—a team led by Tanja Rundek, MD, PhD, sought to investigate the association between metabolic syndrome and carotid stiffness. Dr. Rundek is Assistant Professor of Neurology at Columbia University College of Physicians and Surgeons in New York City.

“We have recently reported that metabolic syndrome is strongly associated with an increased risk of stroke. There has been a tremendous amount of interest in developing cardiovascular ‘surrogate markers and end points’ in order to target high-risk individuals for stroke prevention,” acknowledged Dr. Rundek.

The investigators used data from the Northern Manhattan Study and calculated the change in diameters of right common carotid artery and the difference in systolic and diastolic blood pressure during the past three years. The study cohort consisted of 857 participants (average age, 66; 60% women, 56% Hispanic, 23% black, 21% white). Of the group, 38% were found to have metabolic syndrome. Those with metabolic syndrome had a greater degree of artery stiffness in all gender and race/ethnic groups. Metabolic syndrome was found to be especially dangerous for Hispanics, accounting for nearly 40% of their strokes, the researchers determined.

The average artery stiffness was 21.0 (a reflection of the mechanical stress affecting the arterial wall during the cardiac cycle) among those with metabolic syndrome compared to 1.97 among those without the syndrome. The researchers concluded that the metabolic syndrome is “highly prevalent and significantly associated with carotid stiffness. Increased arterial stiffness may help explain the increased stroke risk in people with metabolic syndrome.”

RACE/ETHNICITY, STROKE RISK, AND METABOLIC SYNDROME

Bernadette Boden-Albala, MPH, DrPH, said the ongoing Northern Manhattan Study of almost 3,300 residents of the city suggests metabolic syndrome is responsible for “35% of strokes seen in Hispanics. That means that if we could eliminate the metabolic syndrome in this population we could reduce the number of strokes by 35%.”

The higher prevalence of vascular risk factors among minorities prompted the research team to investigate the relationship between metabolic syndrome and ischemic stroke among whites, blacks, and Hispanics. The researchers enrolled a cohort of 3,298 community participants (average age, 69; 53% Hispanic, 24% black, and 21% white) of whom more than 42% met the criteria for metabolic syndrome, with the highest prevalence rate among Hispanics (49%).

At the time of her presentation, Dr. Boden-Albala, who is an Assistant Professor of Sociomedical Sciences in Neurology at Columbia, reported that 132 ischemic strokes had been detected in the total group. Overall, adjusting for other risk factors, participants with metabolic syndrome were 1.5 times more likely to have a stroke than were those without the syndrome, the investigators reported.

For Hispanics, having metabolic syndrome more than doubled the risk of stroke, while blacks and whites with the syndrome were 1.1 to 1.2 times as likely to have a stroke. “And for Hispanics, 38% of stroke deaths were attributable to metabolic syndrome —which is huge,” emphasized Dr. Boden-Albala.

Population-based attributable risk due to metabolic syndrome by race/ ethnicity was estimated, and the investigators found that more than a third of strokes in Hispanics may be related to metabolic syndrome; only 6% of strokes in blacks and 1% of strokes in whites may be related to the syndrome. Dr. Boden-Albala’s group believe the findings of the prospective study suggest that metabolic syndrome may be a more potent stroke risk factor for Hispanics than for blacks or whites.

“Understanding race/ethnicity differences on the impact of metabolic syndrome will help us effectively target populations at increased stroke risk,” they said. “We believe [the presence of metabolic syndrome] actually allows a clinician to diagnose people earlier with cardiovascular disease risk and stroke risk,” Dr. Boden-Albala commented.

NR

—Heidi W. Moore

Suggested Reading
Arnett DK, Chambless LE, Kim H, et al. Variability in ultrasonic measurements of arterial stiffness in the Atherosclerosis Risk in Communities study (ARIC). Ultrasound Med Biol. 1999:25:175-180.
Nagai Y, Fleg JL, Kemper MK, et al. Carotid arterial stiffness as a surrogate marker for aortic stiffness: relationship between carotid artery pressure-strain elastic modulus and aortic pulse wave velocity. Ultrasound Med Biol. 1999;2: 181-188.
van Popele NM, Grobbee DE, Bots ML, et al. Association between arterial stiffness and atherosclerosis: the Rotterdam Study. Stroke. 2001;32:454-460.

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