Metabolic Syndrome and Risk of Coronary, Cerebral, and Peripheral Vascular Disease in a Large Dutch Population With Familial Hypercholesterolemia

Rana, Jamal S.; Jansen, Angelique C.M.; Zwinderman, Aeilko H.; Nieuwdorp, Max; Cohen, Emily; Jukema, J. Wouter; Trip, Mieke D.; Kastelein, John J.P.

doi:10.2337/dc05-2530

Cited by 20 publications

(27 citation statements)

References 30 publications

(7 reference statements)

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“…Even after the exclusion of subjects with diabetes, there were graded increases in PAD prevalence with increasing HOMA-IR quartiles, although the associations between HOMA-IR and PAD were no longer statistically significant. Our data support prior observations that PAD is associated with the metabolic syndrome 11,12,36 and glucose intolerance, 13 both surrogate markers of insulin resistance. In contrast to the limited data on the association of insulin resistance and PAD, the link between inflammation and PAD has been well established.…”

Section: Discussionsupporting

confidence: 81%

“…10 The role of insulin resistance in PAD is not well established, although several lines of evidence support a linkage. Insulin resistance contributes significantly to the development of diabetes mellitus, a known risk factor for PAD, 10 and studies have shown that incident PAD may be associated with the metabolic syndrome 11,12 and glucose intolerance, 13 both manifestations of insulin resistance. No prior study has evaluated the relationship between PAD and a direct measurement of insulin resistance.…”

Section: Clinical Perspective P 41mentioning

confidence: 99%

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Association of Insulin Resistance and Inflammation With Peripheral Arterial Disease

et al. 2008

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Background-Although the role of inflammation in the pathophysiology of peripheral arterial disease (PAD) is well established, the contribution of insulin resistance (IR) to PAD is less clear. We hypothesized that IR is associated with PAD and that the presence of IR would influence the association between C-reactive protein (CRP) and PAD, an association established predominantly in healthy individuals. Methods and Results-We analyzed data from 3242 adults in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 who underwent measurement of ankle brachial index, CRP, and fasting glucose and insulin, enabling calculation of homeostasis model of IR (HOMA-IR). Odds ratios (ORs) and 95% CIs were estimated by logistic regression. The mean prevalence of PAD (defined as an ankle brachial index Յ0.9) was 5.5% (SE, 0.47%). HOMA-IR was independently associated with PAD (OR, 2.06; 95% CI, 1.1 to 4.0; Pϭ0.03 for quartile 4, P for trend across quartilesϭ0.047) after adjustment for age, gender, race/ethnicity, hypertension, hyperlipidemia, smoking, body mass index, chronic kidney disease, and CRP. Elevated CRP (Ͼ3 mg/L) also was strongly associated with PAD (OR, 2.2; 95% CI, 1.3 to 3.6; Pϭ0.003 versus CRP Ͻ1 mg/L). Stratifying subjects on the basis of median HOMA-IR, we found that CRP Ͼ3 mg/L was no longer significantly associated with PAD in subjects with IR (OR, 1.3; 95% CI, 0.8 to 2.1; Pϭ0.3, P for interactionϭ0.08). Conclusions-These

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Section: Discussionsupporting

confidence: 81%

Section: Clinical Perspective P 41mentioning

confidence: 99%

Association of Insulin Resistance and Inflammation With Peripheral Arterial Disease

et al. 2008

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“…Only one previous prospective study (Dutch) has reported that the modified NCEP definition predicted PVD in subjects with familial hypercholesterolemia (18). However, the original definition of the metabolic syndrome was not used in this study because of the lack of waist cir- cumference measurement.…”

Section: Statistical Analysesmentioning

confidence: 98%

“…Since these different definitions were published, various prospective studies have reported that the metabolic syndrome defined by the criteria is associated with incidence or mortality of CHD and CVD and stroke (8 -17). However, there are limited data on the effect of the metabolic syndrome on PVD (18). In particular, it is unknown whether the metabolic syndrome predicts PVD above and beyond diabetes.…”

mentioning

confidence: 99%

Metabolic Syndrome and Incident End-Stage Peripheral Vascular Disease

et al. 2007

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OBJECTIVE—We investigated the relationship of the metabolic syndrome and its single components, defined by four different criteria, with peripheral vascular disease (PVD) in a prospective population-based study. RESEARCH DESIGN AND METHODS—The metabolic syndrome was defined according to the World Health Organization (WHO), the National Cholesterol Education Program (NCEP), the International Diabetes Federation (IDF), and the American Heart Association (updated NCEP) criteria. We investigated the relationship of the metabolic syndrome defined by the aforementioned four criteria with PVD (revacularization and amputation) by Cox regression analyses in a Finnish population of 1,212 subjects, aged 65–74 years, with and without diabetes during a 14-year follow-up. RESULTS—The metabolic syndrome defined by the WHO, NCEP, and updated NCEP criteria was associated with a statistically significant risk for incident PVD (n = 57) with adjustment for all confounding variables except for prevalent diabetes (hazard ratios [HRs] from 1.91 to 2.62). After adjustment for prevalent diabetes or after the exclusion of subjects with prevalent diabetes, there was no association between the metabolic syndrome by any criteria and incident PVD. Of the single components of the metabolic syndrome, elevated fasting glucose by the WHO and NCEP criteria (HR 2.35) and microalbuminuria by the WHO definition (2.56) predicted PVD in multivariable models (prevalent diabetes included). CONCLUSIONS—The metabolic syndrome defined by the WHO, NCEP, and updated NCEP criteria predicted incident end-stage PVD in elderly Finns but only when not adjusted for diabetes status. Two of the single components of the metabolic syndrome, elevated fasting plasma glucose and microalbuminuria, predicted PVD. We conclude that the metabolic syndrome predicts PVD but not above and beyond the risk associated with diabetes and microalbuminuria.

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“…The risk to FH patients of developing coronary disease is further increased by the presence of the metabolic syndrome (39) or its individual components, including low HDL-cholesterol (40)(41)(42)(43)(44), high TGs (40), and insulin resistance (45)(46)(47).…”

mentioning

confidence: 99%

Absence of stearoyl-CoA desaturase-1 ameliorates features of the metabolic syndrome in LDLR-deficient mice

Macdonald

Singaraja

Bissada

et al. 2008

Journal of Lipid Research

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A combination of the interrelated metabolic risk factors obesity, insulin resistance, dyslipidemia, and hypertension, often described as the "metabolic syndrome," is known to increase the risk of developing cardiovascular disease and diabetes. Stearoyl-coenzyme A desaturase (SCD) activity has been implicated in the metabolic syndrome, but detailed studies of the beneficial metabolic effects of SCD deficiency have been limited. Here, we show that absence of the Scd1 gene product reduces plasma triglycerides and reduces weight gain in severely hyperlipidemic low density lipoprotein receptor (LDLR)-deficient mice challenged with a Western diet. Absence of SCD1 also increases insulin sensitivity, as measured by intraperitoneal glucose and insulin tolerance testing. SCD1 deficiency dramatically reduces hepatic lipid accumulation while causing more modest reductions in plasma apolipoproteins, suggesting that in conditions of sustained hyperlipidemia, SCD1 functions primarily to mediate lipid stores. In addition, absence of SCD1 partially ameliorates the undesirable hypertriglyceridemic effect of antiatherogenic liver X receptor agonists.Our results demonstrate that constitutive reduction of SCD activity improves the metabolic phenotype of LDLR-deficient mice on a Western diet.

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Metabolic Syndrome and Risk of Coronary, Cerebral, and Peripheral Vascular Disease in a Large Dutch Population With Familial Hypercholesterolemia

Cited by 20 publications

References 30 publications

Association of Insulin Resistance and Inflammation With Peripheral Arterial Disease

Association of Insulin Resistance and Inflammation With Peripheral Arterial Disease

Metabolic Syndrome and Incident End-Stage Peripheral Vascular Disease

Absence of stearoyl-CoA desaturase-1 ameliorates features of the metabolic syndrome in LDLR-deficient mice

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