Assessment of endothelial dysfunction in young healthy first-degree relatives with family history of premature coronary artery disease using vascular doppler ultrasonography

Background: Endothelial dysfunction in young healthy first-degree relatives with family history of premature coronary artery disease was assessed in the present study using vascular doppler ultrasonography.Methods: Thirty young (10-40 years) first degree relatives of 17 patients with premature CAD without risk factors were selected for the study. Age and gender matched healthy subjects were enrolled as controls. Non- invasive assessment of endothelial dysfunction was done by vascular doppler study of brachial artery. Brachial artery diameter, velocity and blood flow were estimated in every study subject and control at rest, after stress and again at rest and after glyceryl-trinitrate (GTN) by vascular Doppler ultrasonography.Results: The percent rise in lumen diameter of brachial artery after stress i.e. reactive hyperaemia, labelled as percent rise in flow mediated dilatation (FMD), was significantly lower in family history group than in controls (8.42±3.47% vs 12.22±4.31%, p<0.05). The statistically significant difference in percent rise in FMD was observed to be consistent across different ages/genders (p<0.05). The mean percent rise in FMD among family history group with positive maternal history (8.06±3.65) was lower as compared to those with positive paternal history (8.57±3.12), but the difference was not statistically significant (p>0.05).Conclusions: Apparently healthy young subjects with family history of premature CAD have impaired endothelium dependent FMD in systemic circulation. Simple, non-invasive, cost-effective vascular doppler ultrasonography is recommended as a potential screening tool to detect subclinical atherosclerosis.

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Abstract 14925: Inverse Association between Family History of Premature Coronary Artery Disease and the Risk of Death in Patients with Coronary Artery Disease

Circulation ◽

10.1161/circ.130.suppl_2.14925 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Ahmed Abdi Ali ◽

Abdel Aziz Shaheen ◽

Danielle A Southern ◽

Mei Zhang ◽

Merril Knudston ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Family History ◽

Clinical Characteristics ◽

System Level ◽

Premature Coronary Artery Disease ◽

Inverse Association ◽

History Of ◽

Premature Cad ◽

Artery Disease

Background: Family history (FHx) of premature coronary artery disease (CAD) is an established cardiovascular risk factor. However the impact of FHx on outcomes of patients with CAD is unclear. Methods & Results: The Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) Program is an inclusive prospective registry of patients undergoing coronary angiography. Between April 2002 and Mar 2013, 99,667 patients were enrolled. 30,030 (30%) patients reported FHx, defined as a first degree relative with premature CAD (males <55, females <65 years). We investigated the association between FHx and all-cause mortality at 1 year, using multivariable logistic regression, adjusting for clinical characteristics, comorbidities, and the extent of CAD. Patients with normal angiography (15.2%) were excluded. Compared to those without FHx, those with FHx were younger (60.1 vs 64.0 years, p<0.0001), more likely female (30.5% vs 29.5%; p=0.0018), and were less likely to have previously diagnosed CAD, congestive heart failure, stroke, or chronic kidney disease (all p<0.0001) Conversely, those with FHx were more likely current smokers (31.8% vs 25.3%) and to have hypertension (68.8% vs 65.5%) and dyslipidemia (75.7% vs 68.1%), all p<0.0001). The indication for angiography was an acute coronary syndrome (ACS) in 55% of both groups (p=0.57), and the extent of CAD was similar. Overall, FHx was associated with reduced 1-year mortality in fully adjusted models (odds ratio [OR] 0.56, 95% CI 0.51 to 0.62). This protective association was present in patients with and without a previous CAD event (OR 0.66 [95% CI 0.60 to 0.78] vs 0.53 [95% CI 0.47 to 0.59], respectively), and in patients with and without an ACS (OR 0.56 [95% CI 0.50 to 0.63] vs 0.56 [95% CI 0.48 to 0.65], respectively). There was slight attenuation of association with age, but FHx remained protective even in those aged 80 or more (OR 0.72, 95% CI 0.57 to 0.90). Conclusion: In patients with angiographic CAD, a family history of premature CAD is associated with lower mortality, independent of clinical characteristics, mode of presentation, and extent of disease. Further investigation of potential patient- and system-level mediators of this seemingly paradoxical relationship is required.

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Abstract 11661: A Family History of Premature Coronary Artery Disease is Associated With Location and Severity of Angiographically Defined Coronary Artery Stenosis

Circulation ◽

10.1161/circ.130.suppl_2.11661 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Muhammad Hammadah ◽

Riyaz S Patel ◽

Danny J Eapen ◽

Ayman Samman Tahhan ◽

Nima Ghasemzadeh ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Family History ◽

Premature Coronary Artery Disease ◽

Left Main ◽

Vessel Stenosis ◽

History Of ◽

Female Relative ◽

Premature Cad ◽

Artery Disease

Introduction: A family history (FH) of premature coronary artery disease (CAD) is an important prognostic risk factor. Emerging evidence suggests that CAD location as well as severity may be heritable. We sought to investigate the association between a FH of premature CAD with the location and severity of angiographically phenotyped CAD. Methods: 2854 patients undergoing coronary angiography were enrolled from the Emory Cardiovascular Biobank. A FH of CAD was defined as having any male or female relative with history of CAD at age ≤55 or ≤65 year old respectively. Coronary angiograms were phenotyped using a 17 segment AHA model. Proximal disease was defined as having ≥70% lesion in the left main or proximal portion of any of the three major epicardial arteries, while CAD severity was assessed by counting the number of vessels with ≥70% stenosis. Results: Among this population (mean age 63±12, male 67%, diabetes 33%), 21% reported a positive FH of premature CAD. After adjustment for age, gender, and traditional cardiovascular risk factors, those with a positive FH were more likely to have significant CAD than those without a positive FH (OR 1.3 (1.1-1.7)). They were 40% more likely to have single vessel (OR 1.4(1.1-1.7)) and up to 80% more likely to have multi-vessel disease (OR 1.8 (1.4-2.4)). In addition, they were also much more likely to have left main (OR 1.9 (1.3-2.8)) and proximal vessel involvement (OR 1.5 (1.2 - 1.9)), but not distal vessel stenosis (OR 1.1 (0.9-1.4)). Conclusions: A FH of CAD is associated with a greater likelihood of multi-vessel and proximal anatomical disease. Whether site specific disease is genetically mediated remains to be explored.

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P3412Risk factors, biomarkers and framingham risk estimate fail to identify presence of subclinical atherosclerosis in young individual with family history of premature coronary artery disease

European Heart Journal ◽

10.1093/eurheartj/ehz745.0286 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Ghadiri ◽

J Leipsic ◽

N Elahi ◽

M Anastasius ◽

A Huang ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Family History ◽

Subclinical Atherosclerosis ◽

Calcium Score ◽

Premature Coronary Artery Disease ◽

Framingham Risk ◽

History Of ◽

Premature Cad ◽

Artery Disease

Abstract Introduction Patients with family history of premature coronary artery disease (CAD) are at increased risk of CAD events at a younger age. Risk factor based approaches and clinical evaluation are most commonly used to assess these individuals. However, it has been recently shown that up to 50% of individual presenting with their first myocardial infarction (MI) were considered to be “low risk” prior to that event. MI is often a result of plaque rupture preceded by progression of subclinical atherosclerosis. Detection of subclinical atherosclerosis may therefore help target prevention of plaque progression. We assessed the value of clinical risk factor, biomarkers and Framingham Risk Score (FRS) in predicting subclinical atherosclerosis in individuals with a family history of premature CAD. Methods From 310 referrals, 222 individuals between the ages of 35 and 55 with a family history of premature CAD (CAD events in first-degree family members (male <55, female <65)) were enrolled for evaluation of risk of CAD. Those with familial hypercholesteremia (possible, probable or definite) were excluded. Patients underwent clinical and risk factor evaluations as well as Cardiac CT or Calcium Score (CS) to assess presence of subclinical / clinical atherosclerosis at the discretion of the treating physician. Results In this pilot, 141 individuals (59% male, mean age 45.9±6.0 years) completed evaluation, and 65 (46%) had evidence of subclinical atherosclerosis on CT coronary angiography or CT calcium score with a mean segment involvement score (SIS) of 2.8 and mean CS of 152, putting them above the 80th percentile for their age and sex. Aside from male sex, age, and smoking history, other traditional risk factors and biomarkers including diabetes mellitus, hypertension, total cholesterol, LDL-C, HDL-C and Cholesterol/HDL-C were not significantly different between those with or without subclinical atherosclerosis (Table 1). Table 1 Conclusion In young individuals with a family history of premature CAD, risk factors, biomarkers, and FRS failed to identify individuals with premature, subclinical atherosclerosis in this pilot study. Detection of subclinical atherosclerosis and early implementation of treatment with the aim of stabilizing plaques and stopping progression might prove vital in reducing events in these individuals. Further studies are warranted.

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Abstract 11134: Subclinical Coronary Plaque Burden in Asymptomatic Relatives of Patients With Documented Premature Coronary Artery Disease

Circulation ◽

10.1161/circ.132.suppl_3.11134 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Morten K Christiansen ◽

Jesper M Jensen ◽

Hans Erik Bøtker ◽

Henrik K Jensen

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Family History ◽

Coronary Atherosclerosis ◽

Coronary Plaque ◽

Plaque Burden ◽

Premature Coronary Artery Disease ◽

First Degree Relatives ◽

Premature Cad ◽

Artery Disease

Introduction: A family history of premature coronary artery disease (CAD) is a well-known risk factor for adverse coronary events with age of onset being inversely related to the degree of heritability. Hypothesis: We hypothesized that asymptomatic first degree relatives, of patients with premature CAD, suffer a high burden of subclinical coronary atherosclerosis. Methods: First degree relatives, aged 30-65 years, of patients with a documented coronary revascularization procedure before the age of 40 years, were invited to participate in the study. Participants were matched by age, sex and absence of a family history, with patients referred for coronary CT angiography (CTA) because of atypical angina or non-anginal chest pain. A pooled blinded analysis was performed. The main outcome measure was the number of plaque-affected coronary segments. Results: 88 relatives and 88 symptomatic controls underwent CTA. Treatment of hypertension and dyslipidemia tended to be more common among controls (p=0.06). 4 relatives reported vague symptoms of which none had angiographic signs of obstructive CAD (any luminal stenosis above 50%). The calculated SCORE risk among relatives was generally low (85% having a 10-year risk of ≤1%). Relatives had significantly (p=0.006) more affected segments than controls (0 segments: 29,6% vs. 48,9%, 1-2 segments: 27,3% vs. 31,8%, 3-5 segments: 23,9% vs. 11,4% and ≥6 segments: 19,3% vs. 8,0%). In a multivariable logistic regression analysis, the presence of any CAD (OR 3.16 (1.50;6.70)) as well as non-calcified plaques (OR 2.2 (1.14;4.26)), mixed plaques (OR 6.77 (2.7;16.98)) and calcified plaques (OR 2.34 (1.01;5.43)) were more frequent. Although increased, the presence of obstructive plaques, however, did not differ statistically significantly between relatives and controls (OR 2.58 (0.85;7.83)). Conclusions: Asymptomatic relatives of patients with premature CAD suffer a high coronary plaque burden even when compared with symptomatic patients with an a priori higher risk of CAD. Our results indicate a strong genetic component in the genesis of coronary atherosclerosis and, moreover, underline the limitations of current guidelines on prevention of CAD.

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Family history of premature coronary artery disease is not associated with coronary artery calcification

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.247 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

G Koulaouzidis ◽

D Charisopoulou

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Family History ◽

Coronary Artery Calcification ◽

Premature Coronary Artery Disease ◽

History Of ◽

Premature Cad ◽

The Mean ◽

Artery Disease ◽

Asymptomatic Individuals

Abstract Funding Acknowledgements Type of funding sources: None. Background Controversy exists regarding the association of family history(FH) of premature coronary artery disease (CAD) with coronary artery calcification (CAC). The purpose of this study was to assess the potential association between family history of premature CAD (<55 years in first-degree male relatives and <65 years in first-degree female relatives) and CAC. Methods A retrospective study of 3613 asymptomatic individuals who underwent assessment of CAC score (CACs) according with the Agatston method. Individuals were selected based on the presence or absence of FH of premature CAD. Individuals with history of hypercholesterolaemia, hypertension, diabetes mellitus or obesity (BMI> 30), smokers (current or previous) were excluded. Furthermore, we excluded subjects with late-onset family history of CAD (>55 years in first-degree male relatives and >65 years in first-degree female relatives). Results Mean age of the cohort was 50.4 ± 9.5 year (74.6% males) and 15.6% reported FH in a parent, sibling or both (prevalence was 12.8% in parents only, 1.9% in siblings only and 0.9% in both parents and siblings). The prevalence of CAC was similar in individuals with FH (35%) and those without (36%), p = 0.2; with no difference in the mean CACs between the two groups, p = 0.4 (Table 1). Individuals with FH in parents only or siblings only had a similar incidence of CAC compared to those without FH (p = 0.9 and 0.7, respectively), with no difference in the mean CACs, p= 0.9 in both. Additionally, the incidence of CAC was not different in individuals with FH in both parents and siblings compared to those without FH (p= 0.1) and again there was no difference in the mean CACs (p = 0.6). Conclusion In asymptomatic individuals with none of the conventional risk factors for atherosclerosis, there was no relationship between the incidence and extent of CAC and the presence of FH of premature CAD. CAC distribution based on FH of CAD No FH Yes FH FH in parents only FH in siblings FH in both Number 3047 566 464 68 34 Males 74.8% 73.3% 74.3% 69.1% 67.7% Age (mean ± SD) 52 ± 9.6 46.9 ± 8.2 46.6 ± 8.1 49.5 ± 8.4 47.3 ± 8.2 Prevalence of CAC 35% 36% 35.2% 36.7% 41% Log-transformed CACs (± SD) 0.5 ± 0.8 0.5 ± 0.8 0.5 ± 0.8 0.5 ± 0.8 0.7 ± 0.9

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