Metabolic syndrome criteria, risk factors and implications for cardiovascular disease

Criteria for metabolic syndrome include five factors with varying benchmarks for children and adults.

The criteria for metabolic syndrome include five factors with varying benchmarks for children and adults.

Three out of five of the following criteria are necessary for a diagnosis of metabolic syndrome in children:

  • Abdominal obesity, defined in children as waist circumference that is more than 90th percentile for gender, age and height
  • High-density lipoprotein (HDL) cholesterol less than 40
  • Triglycerides more than 150mg/dL
  • Systolic blood pressure more than 90th percentile for gender, age and height
  • Fasting glucose greater than or equal to 100 mg/dL

In adults, the criteria are the same, though several of the thresholds differ:

  • Abdominal obesity is defined as a waist circumference of more than 40 inches in men and 35 inches in women
  • Systolic blood pressure over 130
  • HDL under 50 for women and under 40 for men

Overall, metabolic syndrome patients have three times the risk of getting cardiovascular disease and two times the risk of cardiac death.

“That’s why this is important. That’s why we need more counseling and to start prevention right from childhood,” said Jyothi M. Matta, M.D., pediatric cardiologist with Norton Children’s Heart Institute, affiliated with the UofL School of Medicine. “We know pathophysiological changes occur in childhood leading to premature cardiovascular disease. And what is the reason for this? Mostly metabolic syndrome.”

Premature cardiovascular disease is defined as cardiovascular disease in men under 55 and women under 65.

Dr. Matta spoke during a continuing medical education opportunity, “2022 Pediatric Cardiology Update: Metabolic Syndrome.”

Dr. Matta and other specialist physicians see patients in the Norton Children’s Metabolic Syndrome Clinic, a multidisciplinary clinic that aims to prevent acquired heart disease in children. The clinic offers comprehensive care for children with obesity, dyslipidemia and hypertension, with cardiologists, nephrologists, endocrinologists and a general pediatrician dedicated to identifying and addressing cardiovascular risk factors in children.

Metabolic disease also is associated with fatty liver disease with steatosis, fibrosis and cirrhosis; polycystic ovary syndrome; obstructive sleep apnea; and pseudotumor cerebri. In adults, it’s also associated with hepatocellular carcinoma and intrahepatic cholangiocarcinoma, chronic kidney disease, hyperuricemia and gout, and dementia.

The pre-COVID-19 prevalence of metabolic syndrome was 9% to 10% in children, with an obesity rate of 18%. Among adults pre-pandemic, 35% had metabolic syndrome, while 40% were obese.

Risk factors for metabolic syndrome

  • Ethnicity (Native Americans have the highest rate of metabolic syndrome, followed by Hispanics and whites.)
  • Maternal gestational diabetes
  • Low birth weight
  • Short sleep duration because of inflammation and oxidative stress
  • Excessive screen time
  • Low physical activity
  • Lack of whole grain and fiber intake

According to Dr. Matta, factors that can lead to obesity are also risk factors for metabolic syndrome.

“Anything that can cause obesity, you need to be watching out for metabolic syndrome,” Dr. Matta said.

These risk factors include a family history of diabetes, a parent or grandparent with premature cardiovascular disease and a parent with cholesterol over 240.

Other risk factors are childhood obesity, hypertension or prehypertension, dyslipidemia, low HDL, and diabetes or prediabetes. Such exogenous factors as endocrine or kidney disease medications also can cause metabolic syndrome.

Spotting the beginnings of metabolic syndrome

To catch signs of metabolic syndrome early, clinicians should screen for dyslipidemia. The American Academy of Pediatrics recommends all children undergo screening at ages 9 to 11 years and again at 17 to 21.

In parents suspected of homozygous familiar hypercalcemia, children should be screened between birth to 2 years. If there is a family history of cardiovascular disease, or if the patient has chronic liver disease, heart transplant or Kawasaki disease with aneurysms, children should be checked from 2 to 8 years of age and every two years thereafter until puberty, when changing lipid levels cause frequent false negatives.

An estimated 90% of those newly diagnosed with Type 2 diabetes have at least two of the risk factors for metabolic syndrome.

Pathophysiology starts in childhood and has two central components, both in the liver.

Suppression of hepatic glucose production is impaired. The insulin-resistant state results in increased hepatic glucose production and increased glucose output in the blood. There is also an increase in muscle insulin resistance and a decrease in glucose disposal.

At the same time, hepatic lipogenesis is not impaired. In the insulin-resistant state, there is an increase in free fatty acids and triglycerides circulating in the blood, with low HDL and ectopic adipose deposition in the liver and arteries.

The beginning of metabolic syndrome is proinflammation and prothrombotic. With the proinflammatory state, there is increased high-sensitivity C-reactive protein (CRP), inflammatory cytokines, TNF-alpha and interleukin-6. Adiponectin levels are decreased.

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To refer a patient to Norton Children’s Heart Institute for possible treatment at the Norton Children’s Metabolic Syndrome Clinic, visit Norton EpicLink and choose EpicLink referral to Pediatric Cardiology.

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In the prothrombotic state, there are increased antifibrolytic factors such as plasminogen activator inhibitor-1 (PAI-1) and fibrinogen. There are also vascular dysfunction and endothelial dysfunction, leading to microalbuminuria.

Evidence of atherosclerotic vascular changes early in childhood can be seen in carotid artery intima-media thickness on carotid ultrasound. There is also decreased reactivity on the brachial artery and increased arterial stiffness leading to diastolic hypertension and dysfunction later.

These signs point to a risk for stroke, thoracic aortic aneurysm and the beginning of peripheral vascular disease, according to Dr. Matta.

The preferred screening test is a fasting lipid profile, though Dr. Matta recommended clinicians should get whatever lipid profile is available. If the initial test is abnormal, a fasting lipid profile should be repeated in two weeks to three months, depending on the levels.

Pharmacological intervention always should be based on the fasting lipid profile, according to Dr. Matta.

To check for pediatric hypertension, clinicians should get manual blood pressure and check against normal levels for age, gender and height.

From 90th to 95th percentile is prehypertension. If blood pressure is still high after three months of lifestyle modifications do not help after a year, these children should be referred to a subspecialist.

From 95th to 99th percentile is stage 1 hypertension. If blood pressure is still high after three months of lifestyle modifications, these children should be referred to a subspecialist.

Children with blood pressure over the 99th percentile and 5mmHg or greater should be rechecked in a week or referred directly to a subspecialist.

Lifestyle modifications include a decrease in fruit juice intake, a Mediterranean diet low in fat and high in fruits, vegetables, whole grains and olive oil, or a DASH diet, or a high-fiber diet, coupled with 30 minutes of moderate-intensity exercise daily, healthy sleep habits, and limited screen time. (DASH is an acronym for dietary approaches to stop hypertension.)

“Most of these kids have depression or anxiety, so sometimes I refer them to a psychiatric provider for the evaluation,” Dr. Matta said

Pharmacotherapeutic interventions include orlistat, approved for weight loss in children as young as 12, metformin, high-dose fish oil, fibrates, niacin, high-dose statins, ACE inhibitors and calcium channel block, according to Dr. Matta.


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