Familial occurrence of coronary heart disease: Effect of age at diagnosis

doi:10.1016/0002-9149(79)90251-0

The American Journal of Cardiology

Volume 44, Issue 1, July 1979, Pages 60-66

https://doi.org/10.1016/0002-9149(79)90251-0 Get rights and content

Abstract

The occurrence of coronary heart disease and its main risk factors were assessed among the first degree relatives of 309 men from South and East Finland, including 203 men with fatal or nonfatal myocardial infarction and 106 healthy reference men under age 56 years. The younger the patient at the diagnosis of a first myocardial infarction, the more common was coronary heart disease in his parents and siblings. The risk of having coronary heart disease by age 55 was, respectively, 11.4, 8.3 and 1.3 times greater in the South and 6.7, 3.6 and 1.8 times greater in the East for the brothers of patients than for the brothers of reference subjects depending on whether the diagnosis of myocardial infarction in the patient had first been established before the age of 46 years at age 46 to 50 years or at age 51 to 55 years. Hypertension and hyperlipidemia, but none of the other risk factors studied, were most common among the relatives of the youngest patients and diminished in frequency with advancing age of the patient. Most of the strong familial component in coronary heart disease of early onset thus appears to be mediated by familial hyperlipidemias and hypertension. It is suggested that the risk of premature coronary heart disease in the persons at highest risk could be largely eliminated if information about family history were used to identify such persons at an early stage and if they were treated properly for their correctable risk factors.

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This meta-analysis confirms current knowledge of risk factors for PCHD, and identifying these early may reduce CHD in young adults.
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We aimed to systematically compare literature on prevalence of modifiable and non-modifiable risk factors for early compared to late-onset coronary heart disease (CHD).
PubMed, CINAHL, Embase, and Web of Science databases were searched (review protocol registered in PROSPERO CRD42020173216). Study quality was assessed using the National Heart, Lung and Blood Institute tool for observational and case-control studies. Review Manager 5.3 was used for meta-analysis. Effect sizes were expressed as odds ratio (OR) and mean differences (MD)/standardised MD (SMD) with 95% confidence intervals (CI) for categorical and continuous variables.
Individuals presenting with early-onset CHD (age <65 years) compared to late-onset CHD had higher mean body mass index (MD 1.07 kg/m²; 95% CI 0.31−1.83), total cholesterol (SMD 0.43; 95% CI 0.23−0.62), low-density lipoprotein (SMD 0.26; 95% CI 0.15−0.36) and triglycerides (SMD 0.50; 95% CI 0.22−0.68) with lower high-density lipoprotein-cholesterol (SMD 0.26; 95% CI -0.42−-0.11). They were more likely to be smokers (OR 1.76, 95% CI 1.39−2.22) and have a positive family history of CHD (OR 2.08, 95% CI 1.74−2.48). They had lower mean systolic blood pressure (MD 4.07 mmHg; 95% CI -7.36−-0.78) and were less likely to have hypertension (OR 0.47, 95% CI 0.39−0.57), diabetes mellitus (OR 0.56, 95% CI 0.51−0.61) or stroke (OR 0.31, 95% CI 0.24−0.42).
A focus on weight management and smoking cessation and aggressive management of dyslipidaemia in young adults may reduce the risk of early-onset CHD.
There is urgent need to treat atherosclerotic cardiovascular disease risk earlier, more intensively, and with greater precision: A review of current practice and recommendations for improved effectiveness
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Atherosclerotic cardiovascular disease (ASCVD) is epidemic throughout the world and is etiologic for such acute cardiovascular events as myocardial infarction, ischemic stroke, unstable angina, and death. ASCVD also impacts risk for dementia, chronic kidney disease peripheral arterial disease and mobility, impaired sexual response, and a host of other visceral impairments that adversely impact the quality and rate of progression of aging. The relationship between low-density lipoprotein cholesterol (LDL-C) and risk for ASCVD is one of the most highly established and investigated issues in the entirety of modern medicine. Elevated LDL-C is a necessary condition for atherogenesis induction. Basic scientific investigation, prospective longitudinal cohorts, and randomized clinical trials have all validated this association. Yet despite the enormous number of clinical trials which support the need for reducing the burden of atherogenic lipoprotein in blood, the percentage of high and very high-risk patients who achieve risk stratified LDL-C target reductions is low and has remained low for the last thirty years. Atherosclerosis is a preventable disease. As clinicians, the time has come for us to take primordial and primary prevention more serously. Despite a plethora of therapeutic approaches, the large majority of patients at risk for ASCVD are poorly or inadequately treated, leaving them vulnerable to disease progression, acute cardiovascular events, and poor aging due to loss of function in multiple visceral organs. Herein we discuss the need to greatly intensify efforts to reduce risk, decrease disease burden, and provide more comprehensive and earlier risk assessment to optimally prevent ASCVD and its complications. Evidence is presented to support that treatment should aim for far lower goals in cholesterol management, should take into account many more factors than commonly employed today and should begin significantly earlier in life.
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This study characterized and quantified subclinical atherosclerosis by coronary computed tomography angiography (CTA) in first-degree relatives of patients with early onset coronary artery disease (CAD).
A strong family history of CAD is an important risk factor for adverse cardiovascular events. Whether predisposed individuals suffer an increased burden of coronary atherosclerosis and adverse plaque features is not known.
We included 88 healthy middle-aged first-degree relatives from 59 families with early onset CAD. Participants were matched by age and sex with 88 control patients with atypical angina or nonanginal chest pain and no family history of CAD, referred for coronary CTA. A blinded analysis of plaque burden and composition was performed using semiautomated plaque quantification software. The relative differences between the median volumes or the odds ratios (OR) were compared between groups, using a mixed model.
First-degree relatives had significantly more affected coronary segments than controls (0 segments: 30% vs. 49%, respectively; 1 to 2 segments: 27% vs. 32%, respectively; 3 to 4 segments: 18% vs. 6%, respectively; and ≥5 segments: 25% vs. 14%, respectively; p = 0.001). In a multivariate model, the relative differences of total plaque, total calcified plaque (CP), total noncalcified plaque (NCP), and total low-density NCP (LD-NCP) were 5.8 (95% confidence interval [CI]: 2.8 to 11.9), 2.6 (95% CI: 1.5 to 4.5), 5.8 (95% CI: 2.9 to 12.0), and 3.6 (95% CI: 2.1 to 6.1), respectively. The adjusted OR of any positive remodeling plaque or any LD-NCP plaque was 4.2 (95% CI: 1.2 to 14) and 4.2 (95% CI: 1.9 to 9.5), respectively.
Healthy first-degree relatives of patients with early onset CAD have an increased coronary plaque burden compared with symptomatic patients. The plaques display characteristics associated with myocardial ischemia and adverse coronary events.
The 9p21.3 risk locus for coronary artery disease: A 10-year search for its mechanism
2017, Journal of Taibah University Medical Sciences
Citation Excerpt :
The heritability in this study was calculated using Falconer's method to determine the heritability of certain traits or phenotypes based on the difference between twins. Among first-degree relatives with CAD, heritability was estimated at approximately 100% in patients under age 46; whereas, heritability ranged from 15% to 30% in late onset cases of CAD.6 The younger the CAD patient at the diagnosis of the first event of MI, the more common was CAD in his relatives of parents and siblings.
The 9p21.3 risk locus is the first locus to be associated with an increased risk of coronary artery disease (CAD)-related events and many other phenotypes. This locus contains 59 single nucleotide polymorphisms (SNPs) in a region with multiple long range enhancers and long non-coding RNAs (lncRNAs) that affect the expression of neighbouring genes, cyclin-dependent kinase 2A and 2B (CDKN2A and CDKN2B), which are required for controlling vascular smooth muscle cell proliferation and ageing. Several studies have attempted to identify the precise mechanism by which this locus exerts its pathogenic effect to increase the risk of CAD-related events. In this review, we will highlight the major advances in our understanding of the genotype–phenotype correlation at the mechanistic and phenotypic levels. The high population attributable risk of the 9p21.3 risk locus, mechanistic knowledge acquired thus far, and ongoing research efforts could facilitate the design of novel therapeutic molecules to reduce the risk of CAD and its related events.
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2017, Coronary Artery Disease: From Biology to Clinical Practice
Atherosclerosis is a complex disease involving interactions of multiple genetic and environmental factors. It is generally accepted that the inflammatory exacerbation plays an important role in coronary artery disease (CAD). However, recent genome-wide association studies involving over 200,000 cases and controls have led to the identification of over 50 gene risk variants associated with CAD or myocardial infarction. Of note, the vast majority of these genetic risk variants act through unknown mechanisms. Thus, our knowledge on the initiation and progression of CAD remains incomplete. Nevertheless, these findings are of great importance, as they provide further insight into the pathogenesis of atherosclerosis, as well as new targets for the development of novel therapies for the prevention and treatment of CAD.

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^☆: This study was supported by grants from the Finnish State Medical Research Council, the Finnish Heart Association and the Yrjö Jahnsson Foundation, Helsinki, Finland.

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EpidemiologyFamilial occurrence of coronary heart disease: Effect of age at diagnosis☆

Abstract

The familial occurrence of hypertension and coronary artery disease, with observations concerning obesity and diabetes

Ann inter Med

Familial patterns in ischaemic heart disease

Brit J Prev Soc Med

Studies of the male survivors of myocardial infarction due to “essential” atherosclerosis. I. Characteristics of the patients

Can Med Assoc J

Frequency of coronary heart disease and cerebrovascular accidents in parents and sons of coronary heart disease index cases and controls

Am J Epidemiol

Familial factors in premature coronary heart disease-a preliminary report from the Tecumseh Community Health Study

Am J Epidemiol

Coronary disease and its risk factors in families of young men with angina pectoris and in controls

Br Heart J

A stable reagent for the Liebermann-Burchard reaction. Application to rapid serum cholesterol determination

Anal Chem

Fluorometric measurements of triglycerides

Maximum utilization of the life table method in analyzing survival

J Chronic Dis

Epidemiology
Familial occurrence of coronary heart disease: Effect of age at diagnosis☆