Metabolic syndrome identifies normal weight insulin-resistant stroke patients at risk for recurrent vascular disease

Abstract

Background

The obesity paradox refers to the finding in observational studies that patients with obesity have a better prognosis after stroke than normal weight patients.

Aim

To test the hypothesis that there might be important heterogeneity within the obese stroke population, such that those with metabolic syndrome would be at higher risk for stroke or myocardial infarction and all-cause mortality compared to patients without metabolic syndrome.

Methods

The Insulin Resistance Intervention after Stroke trial enrolled non-diabetic patients with a recent ischemic stroke or transient ischemic attack and insulin resistance. We examined the association between metabolic syndrome and outcome risk in patients with normal weight at entry (body mass index (BMI) = 18.5–24.9 kg/m²), overweight (BMI = 25–29.9 kg/m²), or obesity (BMI ≥ 30 kg/m²). Analyses were adjusted for demographic features, treatment assignment, smoking, and major comorbid conditions.

Results

Metabolic syndrome was not associated with greater risk for stroke or myocardial infarction among 1536 patients who were overweight (adjusted hazard ratio (HR), 0.95; 95% confidence interval (CI): 0.69–1.31) or 1626 obese patients (adjusted HR, 1.00; 95% CI: 0.70–1.41). However, among 567 patients with a normal BMI, metabolic syndrome was associated with increased risk for stroke or myocardial infarction (adjusted HR, 2.05; 95% CI: 1.25–3.37), and all-cause mortality (adjusted HR, 1.70; 95% CI: 1.03–2.81) compared to patients without metabolic syndrome.

Conclusions

The presence of metabolic syndrome identified normal weight patients with insulin resistance but no diabetes who have a higher risk of adverse cardiovascular outcomes, compared with patients without metabolic syndrome.

Keywords

Obesity stroke obesity paradox metabolic syndrome insulin resistance prognosis

Get full access to this article

View all access options for this article.

References

Flegal

Kruszon-Moran

Carroll

Fryar

Ogden

. Trends in obesity among adults in the United States, 2005 to 2014. JAMA 2016; 315: 2284–2291.

Klein

Burke

Bray

, et al. Clinical implications of obesity with specific focus on cardiovascular disease. Circulation 2004; 110: 2952–2967.

Bhupathiraju

. Epidemiology of obesity and diabetes and their cardiovascular complications. Circ Res 2016; 118: 1723–1735.

Andersen

Olsen

. Body mass index and stroke: overweight and obesity less often associated with stroke recurrence. J Stroke Cerebrovasc Dis 2013; 22: e576–e581.

Olsen

Dehlendorff

Petersen

Andersen

. Body mass index and poststroke mortality. Neuroepidemiology 2008; 30: 93–100.

Vemmos

Ntaios

Spengos

, et al. Association between obesity and mortality after acute first-ever stroke: the obesity–stroke paradox. Stroke 2011; 42: 30–36.

Kim

Lee

Jung

Lee

Roh

For Korean Stroke Registry investigators, . Dynamics of obesity paradox after stroke, related to time from onset, age, and causes of death. Neurology 2012; 79: 856–863.

Uretsky

Messerli

Bangalore

, et al. Obesity paradox in patients with hypertension and coronary artery disease. Am J Med 2007; 120: 863–870.

Ley

Manson

, et al. Weight history and all-cause and cause-specific mortality in three prospective cohort studies. Ann Int Med 2017; 166: 613–620.

10.

Padwal

Leslie

Lix

Majumdar

. Relationship among body fat percentage, body mass index, and all-cause mortality: a cohort study. Ann Int Med 2016; 164: 532–541.

11.

Dahabreh

Kent

. Index event bias as an explanation for the paradoxes of recurrence risk research. JAMA 2011; 305: 822–823.

12.

Smits

van Kuijk

Leffers

Peeters

Prins

Sep

. Index event bias—a numerical example. J Clin Epidemiol 2013; 66: 192–196.

13.

Banack

Kaufman

. The obesity paradox: understanding the effect of obesity on mortality among individuals with cardiovascular disease. Prev Med 2014; 62: 96–102.

14.

Ovbiagele

Saver

Lynn

Chimowitz

WASID Study Group, . Impact of metabolic syndrome on prognosis of symptomatic intracranial atherostenosis. Neurology 2006; 66: 1344–1349.

15.

Chen

Pan

Jing

, et al. Recurrent stroke in minor ischemic stroke or transient ischemic attack with metabolic syndrome and/or diabetes mellitus. J Am Heart Assoc 2017; 6: e005446.

16.

Liou

Tan

Lin

Wang

Yip

. Metabolic syndrome and three of its components as risk factors for recurrent ischaemic stroke presenting as large-vessel infarction. Eur J Neurol 2008; 15: 802–809.

17.

Zhu

McClure

Lau

, et al. Recurrent vascular events in lacunar stroke patients with metabolic syndrome and/or diabetes. Neurology 2015; 85: 935–941.

18.

Viscoli

Brass

Carolei

, et al. Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the insulin resistance intervention after stroke trial. Am Heart J 2014; 168: 823–829.e826.

19.

Kernan

Viscoli

Furie

, et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 2016; 374: 1321–1331.

20.

Garvey

Mechanick

Brett

, et al. American association of clinical endocrinologists and american college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Prac 2016; 22(Suppl 3): 1–203.

21.

World Health Organization. Waist circumference and waist-hip ratio: report of a WHO expert consultation, Geneva, 8–11 December 2008. Geneva: World Health Organization, 2011.

22.

Alberti

Eckel

Grundy

, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; american heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation 2009; 120: 1640–1645.

23.

Stefan

Schick

Häring

H-U

. Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab 2017; 26: 292–300.

24.

Wildman

Muntner

Reynolds

, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the us population (NHANES 1999–2004). Arch Intern Med 2008; 168: 1617–1624.

25.

Franco

Morais

Cominetti

. Normal-weight obesity syndrome: diagnosis, prevalence, and clinical implications. Nutr Rev 2016; 74: 558–570.

26.

Ruderman

Chisholm

Pi-Sunyer

Schneider

. The metabolically obese, normal-weight individual revisited. Diabetes 1998; 47: 699–713.

27.

Chen

Copeland

Vedanthan

, et al. Association between body mass index and cardiovascular disease mortality in east asians and south asians: pooled analysis of prospective data from the asia cohort consortium. BMJ 2013; 347: f5446.

28.

Hamer

O'Donovan

Stensel

Stamatakis

. Normal-weight central obesity and risk for mortality. Ann Int Med 2017; 166: 917–918.

29.

Arnlov

Ingelsson

Sundstrom

Lind

. Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation 2010; 121: 230–236.

30.

Choi

Cho

Choi

, et al. Higher mortality in metabolically obese normal-weight people than in metabolically healthy obese subjects in elderly Koreans. Clin Endocrinol 2013; 79: 364–370.

31.

Romero-Corral

Somers

Sierra-Johnson

, et al. Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur Heart J 2010; 31: 737–746.

32.

Aung

Lorenzo

Hinojosa

Haffner

. Risk of developing diabetes and cardiovascular disease in metabolically unhealthy normal-weight and metabolically healthy obese individuals. J Clin Endocrinol Metab 2014; 99: 462–468.

33.

Hamer

O'Donovan

Stensel

Stamatakis

. Normal-weight central obesity and risk for mortality. Ann Intern Med 2017; 166: 917–918.

34.

Schneider

Friedrich

Klotsche

, et al. The predictive value of different measures of obesity for incident cardiovascular events and mortality. J Clin Endocrinol Metab 2010; 95: 1777–1785.

35.

Pischon

Boeing

Hoffmann

, et al. General and abdominal adiposity and risk of death in Europe. N Engl J Med 2008; 359: 2105–2120.

36.

Zhang

Rexrode

van Dam

. Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: sixteen years of follow-up in us women. Circulation 2008; 117: 1658–1667.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.47 MB