Insulin resistance independently predicts the progression of coronary artery calcification

doi:10.1016/j.ahj.2009.02.006

American Heart Journal

Volume 157, Issue 5, May 2009, Pages 939-945

https://doi.org/10.1016/j.ahj.2009.02.006 Get rights and content

Background

Change in coronary artery calcification is a surrogate marker of subclinical coronary artery disease (CAD). In the only large prospective study, CAD risk factors predicted progression of coronary artery calcium (CAC).

Methods

We measured CAC at enrollment and after 24 months in a community-based sample of 869 healthy adults aged 60 to 72 years who were free of clinical CAD. We assessed predictors of the progression of CAC using univariate and multivariate models after square root transformation of the Agatston scores. Predictors tested included age, sex, race/ethnicity, smoking status, body mass index, family history of CAD, C-reactive protein and several measures of diabetes, insulin levels, blood pressure, and lipids.

Results

The mean age of the cohort was 66 years, and 62% were male. The median CAC at entry was 38.6 Agatston units and increased to 53.3 Agatston units over 24 months (P < .01). The CAC progression was associated with white race, diabetes, dyslipidemia, hypertension, lower diastolic blood pressure, and higher pulse pressure. After controlling for these variables, higher fasting insulin levels independently predicted CAC progression.

Conclusions

Insulin resistance, in addition to the traditional cardiac risk factors, independently predicts progression of CAC in a community-based population without clinical CAD.

Section snippets

Study sample

The participants in this study were recruited from Kaiser Permanente of Northern California, a large health care system that provides comprehensive care to >3 million people in the San Francisco Bay Area. The details of the recruitment of these subjects have been published previously.16, 17 Briefly, the subjects in the study cohort were between 60 and 72 years old, lived within 50 miles of the research facility, and did not have a diagnosis of cardiovascular disease, cancer, renal failure,

Results

Of the 1,024 healthy older subjects recruited for this study, 967 had a measurement of CAC at their initial visit. The 869 subjects with a baseline CAC measurement who also had a follow-up CAC measurement formed the study group. The follow-up CAC measurements were performed at a median of 23.7 months.

At the time of enrollment, the mean age of the subjects was 66 years, 62% were men, 76% were white, and 10% were African American (Table I). The CAD risk factors were common, including hypertension

Discussion

This study confirms that the traditional cardiac risk factors of diabetes, dyslipidemia, and hypertension independently predict CAC progression in a community-based sample of older adults free of clinical CAD. These results are consistent with the results of the large prospective Multi-Ethnic Study of Atherosclerosis,¹⁰ small prospective studies of diabetic patients,14, 15, 23 and the findings of retrospective studies in other selected populations.13, 24 We also found that insulin resistance

Disclosures

Supported by a grant from the Donald W Reynolds Foundation, Las Vegas, NV.

Acknowledgements

We thank Robert Tibshirani, PhD, for statistical advice.

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Exposure to dietary polychlorinated biphenyls and dioxins, and its relationship with subclinical coronary atherosclerosis: The Aragon Workers' Health Study
2020, Environment International
Experimental evidence has revealed that exposure to polychlorinated biphenyls (PCBs) and dioxins directly impairs endothelial function and induces atherosclerosis progression. In the general population, despite a small number of recent studies finding a link between PCBs, and stroke and myocardial infraction, the association with early coronary atherosclerosis has not been examined yet.
To examine whether dietary exposure to PCBs and dioxins is associated with subclinical coronary atherosclerosis in a middle-aged men.
Cross-sectional analysis comprising 1844 men in their 50 s and free of cardiovascular disease, who participated in the Aragon Workers' Health Study (AWHS). Individual dietary exposures to PCBs and dioxins were estimated by the contaminant’s concentration in food coupled with the corresponding consumption and then participants were classified into quartiles of consumption. Coronary artery calcium score (CACS) was assessed by computerized tomography. We conducted ordered logistic regressions to estimate the odds ratio (OR) and 95% confidence intervals (CIs) for progression to the categories of more coronary artery calcium, adjusting for potential confounders.
Among the participants, coronary calcium was not shown in 60.1% (n = 1108), 29.8% had a CACS > 0 and <100 (n = 550), and the remaining 10.1% (n = 186) had a CACS ≥ 100. Compared with those in the first quartile of PCBs exposure, those in the fourth one had an increased odds for having coronary calcium (OR 2.02, 95% CI [1.18, 3.47], p trend 0.019) and for having progressed to categories of more intense calcification (OR 2.03, 95% CI [1.21, 3.40], p trend 0.012). However, no association was found between dietary dioxins exposure and prevalent coronary artery calcium.
In this general male population, dietary exposure to PCBs, but not to dioxins, was associated with a higher prevalence of coronary calcium and to more intense subclinical coronary atherosclerosis. PCBs exposure seems to increase the risk of coronary disease in men from the very early stages.
Pathophysiology and Prevention of Heart Disease in Diabetes Mellitus
2018, Current Problems in Cardiology
Diabetes mellitus (DM) has become a public health problem worldwide, and it has large implications for cardiovascular disease (CVD). In this article, we discuss the etiology and pathophysiology of CVD in DM including the effects of abnormal glucose homeostasis, genetic factors, epigenetics, apoptosis, common pathophysiological mechanisms shared by both DM and CVD, and contributions of other comorbidities. We then cover the pathogenesis of both atherosclerotic disease and cardiomyopathy in relation to DM. Finally, we discuss the prevention of heart disease in DM with a focus on hypertension and dyslipidemia management, weight loss, lifestyle changes, antiplatelet therapy, and glycemic control.
Cardiac Society of Australia and New Zealand Position Statement: Coronary Artery Calcium Scoring
2017, Heart Lung and Circulation
Coronary Artery Calcium Scoring (CAC) is a non-invasive quantitation of coronary artery calcification using computed tomography (CT). It is a marker of atherosclerotic plaque burden and an independent predictor of future myocardial infarction and mortality.
Coronary Artery Calcium Scoring provides incremental risk information beyond traditional risk calculators (eg. Framingham Risk Score). Its use for risk stratification is confined to primary prevention of cardiovascular events, and can be considered as “individualised coronary risk scoring” for those not considered to be of high or low risk. Medical practitioners should carefully counsel patients prior to CAC. Coronary Artery Calcium Scoring should only be undertaken if an alteration in therapy including embarking on pharmacotherapy is being considered based on the test result.
Patient Groups to Consider Coronary Calcium Scoring:
- 1.
  CAC is of most value in intermediate risk patients (absolute 10-year cardiovascular risk of 10–20%) who are asymptomatic, do not have known coronary artery disease and aged 45–75 years, where it has the ability to reclassify patients into lower or higher risk groups.
- 2.
  It may also be considered for lower risk patients (absolute 10-year cardiovascular risk 6–10%) particularly in those where traditionally risk scores under estimate risk e.g. especially in the context of family history of premature cardiovascular disease (CVD) and possibly in patients with diabetes aged 40 to 60 years old.
Patient Groups in Whom Coronary Calcium Scoring Should Not be Considered:
Coronary Artery Calcium Scoring is not recommended for patients who are:
- 1.
  At very low risk (<5% absolute 10 year risk); or,
- 2.
  High risk ( >20% absolute 10 year risk) – as testing is unlikely to alter the recommended management. This includes some patients who are automatically considered to be high risk (eg. diabetics over 60 years old or diabetics with albuminuria, chronic kidney disease (eGFR <45 mL/min), BP >180/110, familial hypercholesterolaemia and cholesterol >7.5 mmol/L) and therefore should be managed aggressively with optimal medical therapy; or
- 3.
  Symptomatic or previously documented coronary artery disease.
Interpretation of CAC
CAC = 0 A zero score confers a very low risk of death, <1% at 10 years.
CAC = 1-100 Low risk, <10%
CAC = 101-400 Intermediate risk, 10–20%
CAC = 101-400 & >75th centile. Moderately high risk, 15–20%
CAC >400 High risk, >20%
Management Recommendations Based on CAC
Optimal diet and lifestyle measures are encouraged in all risk groups and form the basis of primary prevention strategies. Patients with moderately-high or high risk based on CAC score are recommended to receive preventative medical therapy such as aspirin and statins. The evidence for pharmacotherapy is less robust in patients at intermediate levels of CAC 100–400, with modest benefit for aspirin use; though statins may be reasonable if they are above 75th centile. Aspirin and statins are generally not recommended in patients with CAC <100.
Repeat CAC Testing
In patients with a CAC of 0, a repeat CAC may be considered in 5 years but not sooner.
In patients with positive calcium score, routine re-scanning is not currently recommended. However, an annual increase in CAC of >15% or annual increase of CAC >100 units are predictive of future myocardial infarction and mortality.
Cost Effectiveness of CAC Based Primary Prevention Recommendations:
There is currently no data in Australia and New Zealand that CAC is cost-effective in informing primary prevention decisions. Given the cost of testing is currently borne entirely by the patient, discussion regarding the implications of CAC results should occur before CAC is recommended and undertaken.
Progression of coronary artery calcification is stronger in poorly than in well controlled diabetes: Results from the Heinz Nixdorf Recall Study
2017, Journal of Diabetes and its Complications
To assess associations between HbA1c and progression of coronary artery calcification (CAC) in persons with and without diabetes.
In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany (N = 3453, aged 45–74 years), CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. At baseline, participants were divided into five groups: poorly (HbA1c ≥ 7.0%) and well (HbA1c < 7.0%) controlled previously known diabetes (group I/II); no previously known diabetes with HbA1c ≥ 6.5% (group III), HbA1c 5.7–6.4% (group IV), and HbA1c < 5.7% (group V). We fitted linear, logistic and robust Poisson regression models to assess associations between diabetes group and PF₅ (factor by which CAC after 5-year follow-up is larger than baseline CAC), and categories of CAC change, respectively.
Relative to group V, adjusted percentage increase of the geometric mean of PF₅ (95% CI) was: 69.1% (33.9%;113.6%), 15.4% (− 5.6%;41.1%), − 4.1% (− 22.2%;18.2%), 4.2% (− 5.4%;14.8%) for groups I–IV, respectively. The corresponding odds ratios for annual CAC increase ≥ 100 Agatston units (reference: < 10) were 10.0 (4.8;20.6), 4.0 (2.1;7.6), 1.5 (0.7;3.2), and 1.1 (0.7;1.8).
In known diabetes, CAC progression was stronger in poor diabetes control. For newly detected diabetes diagnosed by HbA1c ≥ 6.5%, associations with CAC progression were weak.
Sugar-sweetened carbonated beverage consumption and coronary artery calcification in asymptomatic men and women
2016, American Heart Journal
Sugar-sweetened carbonated beverage consumption has been linked to obesity, metabolic syndrome, type 2 diabetes, and clinically manifest coronary heart disease, but its association with subclinical coronary heart disease remains unclear. We investigated the relationship between sugar-sweetened carbonated beverage consumption and coronary artery calcium (CAC) in a large study of asymptomatic men and women.
This was a cross-sectional study of 22,210 adult men and women who underwent a comprehensive health screening examination between 2011 and 2013 (median age 40 years). Sugar-sweetened carbonated beverage consumption was assessed using a validated food frequency questionnaire, and CAC was measured by cardiac computed tomography. Multivariable-adjusted CAC score ratios and 95% CIs were estimated from robust Tobit regression models for the natural logarithm (CAC score +1).
The prevalence of detectable CAC (CAC score >0) was 11.7% (n = 2,604). After adjustment for age; sex; center; year of screening examination; education level; physical activity; smoking; alcohol intake; family history of cardiovascular disease; history of hypertension; history of hypercholesterolemia; and intake of total energy, fruits, vegetables, and red and processed meats, only the highest category of sugar-sweetened carbonated beverage consumption was associated with an increased CAC score compared with the lowest consumption category. The multivariable-adjusted CAC ratio comparing participants who consumed ≥5 sugar-sweetened carbonated beverages per week with nondrinkers was 1.70 (95% CI, 1.03-2.81). This association did not differ by clinical subgroup, including participants at low cardiovascular risk.
Our findings suggest that high levels of sugar-sweetened carbonated beverage consumption are associated with a higher prevalence and degree of CAC in asymptomatic adults without a history of cardiovascular disease, cancer, or diabetes.
Increased risk for development of coronary artery calcification in insulin-resistant subjects who developed diabetes: 4-year longitudinal study
2016, Atherosclerosis
Citation Excerpt :
The use of CACS as a simple and safe surrogate marker for subclinical atherosclerosis is increasing. Recent studies have reported an association between an increased risk of CAC and high HbA1c levels in subjects with insulin resistance [17–23]. They showed a good correlation between insulin resistance and high HbA1c with CAC development and progression.
Coronary artery calcification (CAC) is considered a surrogate marker for atherosclerotic burden. The aim of this study was to analyze the risk of incident CAC associated with diabetes development in non-diabetic subjects with zero CAC score (CACS) at baseline.
2076 non-diabetic participants (mean age 40 years) in a health screening program in whom CACS were repeatedly measured by multi-detector computed tomography in four years of intervals and with zero CACS at baseline, were retrospectively analyzed. Glycemic status was assessed in both years, with subjects divided into three groups: subjects with ‘no progression’, ‘normal to impaired fasting glucose (IFG)’ and ‘progression to diabetes’. Insulin resistance was assessed by homeostasis model assessment-insulin resistance (HOMA-IR) index.
Over 4 years, 204 subjects (9.8%) developed CAC. Subjects who developed diabetes showed the highest proportion of subjects with incident CAC among the three groups (21.0% vs. 9.3 and 10.4% in non-progressors and subjects from normal to IFG). The subjects with HOMA-IR level in higher half at baseline showed significantly increased risk for incident CAC in subjects who progressed from normal to IFG and in subjects who developed diabetes (1.740; 95% CI 1.014–2.985, 2.449; 95% CI 1.159–5.174) even after adjustment for confounding variables, whereas subjects with HOMA-IR level in lower half at baseline showed no significantly increased risk for incident CAC even in subjects who developed diabetes.
In this non-diabetic population, we found that increased risk for incident CAC in relation to diabetes development over 4 years was pronounced only in subjects with insulin resistance at baseline.

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: Submission to the American Heart Journal under the classification of Clinical Investigations.

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Clinical InvestigationCoronary Artery DiseaseInsulin resistance independently predicts the progression of coronary artery calcification

Background

Methods

Results

Conclusions

Section snippets

Study sample

Results

Discussion

Disclosures

Acknowledgements

Am J Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Atherosclerosis

Clin Cornerstone

Am J Med Sci

Probabilistic model for prediction of angiographically defined obstructive coronary artery disease using electron beam computed tomography calcium score strata

Circulation

Coronary calcium as a predictor of coronary events in four racial or ethnic groups

N Engl J Med

Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy

Arterioscler Thromb Vasc Biol

Accelerated coronary artery calcification in mildly reduced renal function of high-risk hypertensives: a 3-year prospective observation

J Hypertens

Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography

N Engl J Med

Progression of subclinical coronary atherosclerosis: does obesity make a difference?

Circulation

Clinical Investigation
Coronary Artery Disease
Insulin resistance independently predicts the progression of coronary artery calcification