Excess Coronary Artery Disease Risk Research Articles

Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes

Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to estimate the causal effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans and selected 2 SNPs to be used as instruments. We included heel bone mineral density and hip fracture risk as positive control outcomes. Public GWAS and UK Biobank patient-level data were used for the study outcomes, which include cardiovascular events, risk factors, and biomarkers. Lower sclerostin levels were associated with higher bone mineral density and 85% reduction in hip fracture risk. However, genetically predicted lower sclerostin levels led to 25–85% excess coronary artery disease risk, 40% to 60% increased risk of type 2 diabetes, and worse cardiovascular biomarkers values, including higher triglycerides, and decreased HDL cholesterol levels. Results also suggest a potential (but borderline) association with increased risk of myocardial infarction. Our study provides genetic evidence of a causal relationship between reduced levels of sclerostin and improved bone health and fracture protection, but increased risk of cardiovascular events and risk factors.

Diabetic heart disease: A clinical update.

Diabetes mellitus (DM) significantly increases the risk of heart disease, and DM-related healthcare expenditure is predominantly for the management of cardiovascular complications. Diabetic heart disease is a conglomeration of coronary artery disease (CAD), cardiac autonomic neuropathy (CAN), and diabetic cardiomyopathy (DCM). The Framingham study clearly showed a 2 to 4-fold excess risk of CAD in patients with DM. Pathogenic mechanisms, clinical presentation, and management options for DM-associated CAD are somewhat different from CAD among nondiabetics. Higher prevalence at a lower age and more aggressive disease in DM-associated CAD make diabetic individuals more vulnerable to premature death. Although common among diabetic individuals, CAN and DCM are often under-recognised and undiagnosed cardiac complications. Structural and functional alterations in the myocardial innervation related to uncontrolled diabetes result in damage to cardiac autonomic nerves, causing CAN. Similarly, damage to the cardiomyocytes from complex pathophysiological processes of uncontrolled DM results in DCM, a form of cardiomyopathy diagnosed in the absence of other causes for structural heart disease. Though optimal management of DM from early stages of the disease can reduce the risk of diabetic heart disease, it is often impractical in the real world due to many reasons. Therefore, it is imperative for every clinician involved in diabetes care to have a good understanding of the pathophysiology, clinical picture, diagnostic methods, and management of diabetes-related cardiac illness, to reduce morbidity and mortality among patients. This clinical review is to empower the global scientific fraternity with up-to-date knowledge on diabetic heart disease.

Postmenopausal Hormone Therapy and Its Association with Breast Cancer.

With the cessation of estrogen and progesterone at menopause, the hormone withdrawal affects various systems in the woman's body. In earlier days, menopausal hormone therapy (HT) was prescribed for primary prevention of coronary artery disease (CAD) and osteoporosis, which were thought to be because of estrogen deprivation and epidemiologic data supported a beneficial effect of estrogen on the heart and bone. Later on, robust data from the Women's Health Initiative study comparing two HT trials demonstrated adverse outcomes in terms of excess risk of CAD, stroke, venous thromboembolism, and breast cancer. Even with risk stratification based on family history, approximately only 15% of women diagnosed with breast cancer have such a risk factor. This implies that family history will not be elicited in more than 85% of women who develop breast cancer. Literature review suggests that the prior use of conjugated equine estrogen (CEE) alone has the potential to be effective as an intervention, leading to a reduction in mortality due to breast cancer. Therefore, it is time to reevaluate the risk reduction strategies for breast cancer that are currently in practice. In terms of absolute numbers, for every 10,000 person-years of prior use of CEE alone, there would be only two fewer deaths from breast cancer and two fewer deaths secondary to its sequelae. This translates into a significant number of women in our country with a population of 1.38 billion (of which 48%, nearly 650 million, are women).

448-P: Predictors and Their Impact on Coronary Artery Disease (CAD) According to Glucose Tolerance Status (GTS) and Prior CAD: Historical Cohort Study in Japan

Although GTS, prior CAD and other traditional risk factors independently affect incidence of subsequent CAD, their impact in the same cohort has been scantly studied. We analyzed a nationwide claims-based database of 138,162 men aged 18-72 y in 2008-14. Participants were classified as normal glucose tolerance (NGT, n=78,230), prediabetes (PreDM, n=45,610) or diabetes mellitus (DM, n=14,322) based on blood tests and prescriptions and with prior (CAD+) or without prior CAD (CAD-) based on ICD-10 codes and questionnaires. Among CAD-, management of traditional risks differed from those with and without CAD events, while such differences were weaker in preDM and DM with CAD+. Cox regression model showed that PreDM and DM confer approximately 1.2- and 2.8-fold excess risk of CAD, respectively, compared with CVD- with NGT. CAD+ confers approximately a 5- to 8-fold increased risk. Most traditional risks were independently associated with subsequent CAD in the CAD- group regardless of GTS. Conversely, in the CAD+ group, their impact was weakened and only HDL-C was a significant risk factor for future CAD in those with DM and CAD+ (Table). Thus, the impact of known risks on subsequent CAD differs markedly according to GTS and CAD+. Those with CAD+ and glucose abnormality, especially DM, need treatment residual risk factors as well as traditional risk factors. Disclosure M. Kitazawa: None. K. Fujihara: None. T. Osawa: None. M. Yamamoto: None. M. Harada: None. M. Kaneko: None. Y. Matsubayashi: None. T. Yamada: None. N. Yamanaka: None. H. Seida: None. W. Ogawa: Consultant; Self; Abbott. Research Support; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Lilly Diabetes, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.

Comparative Study of Risk Factors Among the Male and Female Patients with Acute Myocardial Infarction Admitted in CCU of Sahid Gangalal National Heart Centre

The role of major cardiovascular risk factors in the development of coronary artery disease (CAD) is well established and is fairly similar in both sexes. However, CAD is markedly more common in male than in female, and this is due to more risk factors, especially smoking and dyslipidemia, in male. In this study, we aim to investigate the five major risk factors as defined by ACC-AHA namely, advancing age, smoking, hypertension, diabetes and dyslipidemia, in the MI patients admitted in CCU, SGNHC from Jan 1 to June 30th 2008 and to compare whether the association of those risk factors with CAD risk is similar in male and female. There were altogether 283 MI patients, Male 208 (73%) and Female 75 (27%). Advancing age was the most common comprising 85.2% followed by smoking 55.5%, Hypertension 48.1%, Dyslipidemia 47% and Diabetes 24.7%. Smoking, dyslipidemia and advancing age were significantly more common in male. Male patients have significantly more risk factors than female. There was trend towards the greater number of high total cholesterol and low HDL in male patients. Advancing age (Male 45 yrs, Female 55 yrs) is the commonest risk factor of CAD. Smoking and dyslipidemia (especially high total cholesterol and low HDL) are significantly more common in male which might have contributed markedly to the excess CAD risk in males.

Coronary artery disease in a rural population of Bangladesh: is dyslipidemia or adiposity a significant risk?

Background and Aims: The prevalence of cardiovascular diseases (CVD) are on the increase worldwide and more in the developing countries. Coronary artery disease (CAD) constitutes the major brunt of CVD. Despite the increasing morbidity and mortality, Bangladesh has a few published data on CAD in rural population. This study addressed the prevalence of CAD and its risk factors in rural population of Bangladesh.Study methods: Sixteen villages were purposively selected in a rural area. A population census was conducted in the selected area. The census yielded eligible participants, who reached at least eighteen years of age. Those who willingly consented to participate were enlisted. Each participant was interviewed regarding CAD risk (age, sex, social class, occupation, illness, family history). Anthropometry (height, weight, waist- and hip-girth) was recorded. Resting blood pressure (BP) was measured. Blood sample was collected for fasting blood glucose (FBG), total cholesterol (Chol), triglycerides (Tg), low density lipoproteins (LDL), very low density lipoproteins (VLDL) and high density (HDL). All participants having FBG>5.5mmol/l or systolic (SBP) ?135 or diastolic BP (DBP) ?85mmHg underwent electrocardiography (ECG). A team of cardiologists selected and accomplished exercise tolerance test (ETT) and echocardiography (Echo).Results: The prevalence of CAD was 4.5% (95% CI: 3.85 – 5.15). Compared with the female (3.5%, CI, 2.76 – 4.24) the male participants had significantly higher prevalence of CAD (6.0%, CI, 4.83 – 7.13). Comparison of characteristics between participants with and without CAD showed that age, SBP, DBP and FBG were significantly higher in CAD group. Bivariate analysis showed that age, sex, social class, glycemic status, metabolic syndrome (MetS) and smoking were significantly related to CAD. Stepwise logistic regression proved only male sex, rich social class, hypertension and diabetes had independent risk of CAD; whereas, age, obesity and dyslipidemia were proved not significant.Conclusions: The study concludes that the prevalence of CAD in a Bangladeshi rural population is comparable to other developed countries. The male sex, rich social class, hypertension and diabetes were proved to have excess risk of CAD. Neither obesity nor dyslipidemia were found significant for CAD. The younger people had similar risk as the aged ones, which necessitate primordial and primary prevention of CAD. Further study may be undertaken, which should include and consider physical activity and diet; and if possible, Creactive protein, Vitamin D and homocysteine level.IMC J Med Sci 2017; 11(2): 61-69

Elevated lipoprotein(a), hypertension and renal insufficiency as predictors of coronary artery disease in patients with genetically confirmed heterozygous familial hypercholesterolemia

BackgroundFamilial hypercholesterolemia (FH) is characterized by elevated LDL-cholesterol and increased risk of premature coronary artery disease (CAD). Lipoprotein(a) [Lp(a)] increases CAD in FH, although the independence of this association relative to other CAD risk factors remains unclear. In this study, we examined the association between Lp(a) and other cardiovascular risk factors and prevalent CAD in patients with FH. MethodsA cross-sectional study of 390 patients with genetically confirmed FH were studied. Clinical and biochemical parameters of FH patients with and without CAD were compared. ResultsFH patients with CAD were older and more often male and had a higher prevalence of hypertension, smoking, diabetes, obesity, reduced eGFR, and elevated plasma Lp(a) and pre-treatment LDL-cholesterol and triglyceride (or low HDL-cholesterol) than FH patients without CAD (P<0.05 for all). In univariate analyses, age, male gender, smoking, hypertension, reduced eGFR, diabetes, obesity, plasma creatinine, Lp(a) and pretreatment LDL-cholesterol, triglycerides and HDL-cholesterol levels were significant predictors of CAD in the FH patients (P<0.05 for all). Elevated LDL-cholesterol, raised Lp(a), hypertension and reduced eGFR remained significant independent predictors of CAD (P<0.05 for all) in FH after adjusting for other modifiable risk factors. ConclusionsElevated Lp(a), hypertension and renal insufficiency are independent risk factors beyond elevated pretreatment LDL-cholesterol which predict CAD in patients with FH. In spite of the cross-sectional design of our study, we propose the need for identifying and managing these abnormalities to reduce excess CAD risk in FH patients. However, this proposal remains to be formally tested in a prospective study.

Carotid intima media thickness and low high-density lipoprotein (HDL) in South Asian immigrants: could dysfunctional HDL be the missing link?

IntroductionSouth Asian immigrants (SAIs) in the US exhibit higher prevalence of coronary artery disease (CAD) and its risk factors compared with other ethnic populations. Conventional CAD risk factors do not explain the excess CAD risk; therefore there is a need to identify other markers that can predict future risk of CAD in high-risk SAIs. The objective of the current study is to assess the presence of sub-clinical CAD using common carotid artery intima-media thickness (CCA-IMT), and its association with metabolic syndrome (MS) and pro-inflammatory/dysfunctional HDL (Dys-HDL).Material and methodsA community-based study was conducted on 130 first generation SAIs aged 35–65 years. Dys-HDL was determined using the HDL inflammatory index. Analysis was completed using logistic regression and Fisher's exact test.ResultsSub-clinical CAD using CCA-IMT ≥ 0.8 mm (as a surrogate marker) was seen in 31.46%. Age and gender adjusted CCA-IMT was significantly associated with type 2 diabetes (p = 0.008), hypertension (p = 0.012), high-sensitivity C-reactive protein (p < 0.001) and homocysteine (p = 0.051). Both the presence of MS and Dys-HDL was significantly correlated with CCA-IMT, even after age and gender adjustment. The odds of having Dys-HDL with CCA-IMT were 5 times (95% CI: 1.68, 10.78).ConclusionsThere is a need to explore and understand non-traditional CAD risk factors with a special focus on Dys-HDL, knowing that SAIs have low HDL levels. This information will not only help to stratify high-risk asymptomatic SAI groups, but will also be useful from a disease management point of view.

Hyperclycemia, Young Age, Altered Sleep Habits: The Three Shifting Paradigms of Coronary Artery Disease Risk Stratification

The study was undertaken to estimate the risk factors age, gender, race, obesity (BMI), glycemic status (prediabetes, diabetes), exercise and psychosocial factors (sleep, sadness) related to coronary artery disease (CAD). The data set for this study is the National Health Interview Survey (NHIS), which is a large scale, cross sectional, voluntary, household interview survey maintaining data on health status, health care access and progress towards achieving the national health objectives in the USA. A total of 26,965 (male/female =55.8/ 44.2%) subjects were included in the study. Of them, 79.9% were less than 65 years of age. Regarding obesity, overweight, obese and morbid obese were 34.8, 17.3 and 11.0%, respectively. Sadness of any degree was reported in 28%. Sleep duration was found &lt;5h/d in 8.7% and &gt; 9h/d in 9.7%. Heart disease was reported in 4.9%. About 10% were reported to have diabetes and 4.1% prediabetes. 40% of the respondents’ maintained exercise once per week and only 12.8% maintained 10 or more times per week. Logistic regression estimated that compared with the non-diabetics, the subjects with prediabetes (OR 3.27, 95% CI, 2.32-4.59) and diabetes (OR 6.44 95% CI, 5.21-7.96) had excess risk of CAD, more significant in the younger subjects (&lt;65y) than in the older (&gt;65y). The risk of CAD was found significant in both prediabetes (OR 2.47, 95% CI, 1.44-4.23) and diabetes (OR 3.03, 95% CI, 2.16-4.24) as compared with nondiabetic group who slept &gt;9h a day. The subjects with prediabetes or diabetes had excess risk for CAD compared with the non-diabetic subjects, which was more marked in the younger people. Again, compared with the non-diabetic people, the subjects with prediabetes or diabetes, having less sleep or excess sleep, had excess risk for CAD. Further study may confirm our findings. DOI: http://dx.doi.org/10.3329/imcj.v6i2.14727 Ibrahim Med. Coll. J. 2012; 6(2): 39-45

Apo lipoprotein A1 gene polymorphisms predict cardio-metabolic risk in South Asian immigrants.

Objectives: Coronary artery disease (CAD) is a leading cause of death globally with increasing burden in South Asians in the US. Specific genetic variants that influence CAD have not been fully assessed in South Asian Immigrants. The goal is to identify Apo lipoprotein A1 (APOA1) gene polymorphisms and their association with CAD risk factors, metabolic syndrome and dysfunctional HDL (Dys-HDL). Methods: A community-based study on South Asians aged 35-65 years without CAD was conducted. APOA1 gene sequencing was performed and genotypes compared with cardiovascular findings. Results: The prevalence of metabolic syndrome and dysfunctional-HDL was 29.7% and 26%, respectively. Six novel APOA1 gene single nucleotide peptides (SNPs) were analyzed. Three of the six SNPs (G2, G3, and G5) were found to be associated with metabolic syndrome; G2 (T655C) (p=0.044), G3 (T756C) (p=0.037) and G5 (T1001C) (p=0.037). APOA1 gene SNP G1 (T319C) was highly correlated with low HDL levels (p=0.001). In our study, both associations of APOA1 SNPs with metabolic syndrome and low HDL remained after age-adjustment. Conclusion: Discovery of novel gene polymorphisms will help to understand further the causes of excess CAD risk in South Asians so that preventative strategies targeted to high-risk group can be developed.

Apo Lipoprotein A1 Gene Polymorphisms Predict Cardio-Metabolic Risk in South Asian Immigrants

Objectives: Coronary artery disease (CAD) is a leading cause of death globally with increasing burden in South Asians in the US. Specific genetic variants that influence CAD have not been fully assessed in South Asian Immigrants. The goal is to identify Apo lipoprotein A1 (APOA1) gene polymorphisms and their association with CAD risk factors, metabolic syndrome and dysfunctional HDL (Dys-HDL).Methods: A community-based study on South Asians aged 35-65 years without CAD was conducted.APOA1gene sequencing was performed and genotypes compared with cardiovascular findings.Results: The prevalence of metabolic syndrome and dysfunctional-HDL was 29.7% and 26%, respectively. Six novelAPOA1gene single nucleotide peptides (SNPs) were analyzed. Three of the six SNPs (G2, G3, and G5) were found to be associated with metabolic syndrome; G2 (T655C) (p=0.044), G3 (T756C) (p=0.037) and G5 (T1001C) (p=0.037).APOA1gene SNP G1 (T319C) was highly correlated with low HDL levels (p=0.001). In our study, both associations ofAPOA1SNPs with metabolic syndrome and low HDL remained after age-adjustment.Conclusion: Discovery of novel gene polymorphisms will help to understand further the causes of excess CAD risk in South Asians so that preventative strategies targeted to high-risk group can be developed.

Coexistence of Visceral Fat and Multiple Risk Factor Accumulations is Strongly Associated with Coronary Artery Disease in Japanese (The VACATION-J Study)

Multiple risk factor syndrome is a target for the prevention of coronary artery disease (CAD). A cluster of multiple risk factors, such as hypertension, glucose intolerance, and/or dyslipidemia, is encountered in Japanese without and with excess visceral fat. The present study investigated the relationship between multiple risk factor accumulation and CAD in Japanese without and with visceral fat accumulation. The study subjects comprised 257 Japanese with suspected CAD (males/females= 153/ 104), who underwent 64-row multislice computed tomography (CT) coronary angiography and visceral fat area (VFA) measurement by CT. Based on the Japanese criteria for visceral fat accumulation, they were divided into those with VFA <100 and ≥10 cm(2). In subjects with VFA <100 cm(2), the age- and sex-adjusted odds ratios (ORs) for 2 and 3 risk factors were 5.33 (95% confidence intervals; 1.04-27.38, p=0.0449) and 4.07 (0.72-23.15, p=0.1138), respectively, compared with VFA <100 cm(2) and 0 risk factor set at 1.0 (p=0.0569 for trend). In contrast, the respective ORs for subjects with VFA ≥100 cm(2) were much higher [6.46 (1.25-33.44, p=0.0261) and 20.42 (3.60-115.73, p=0.0007)] (p<0.0001 for trend). The multivariate adjusted model demonstrated a significant relative excess CAD risk of 1.08 (p=0.0484) and 5.01 (p<0.0001) for the interactions of 2 risk factors and VFA ≥100 cm(2), and 3 risk factors and VFA ≥100 cm(2), whereas multiple risk factor accumulation was not related with the increase of CAD risk in subjects with VFA <100 cm(2). Coexistence of visceral fat and risk factor accumulations is strongly associated with CAD in Japanese.

Heart in Diabetes: A Microvascular Disease

Diabetes currently affects about 5% of world’s populations, and its prevalence is rapidly increasing particularly in elderly subjects. Because over 80% of all diabetic subjects have type 2 diabetes, the increase in the number of individuals with diabetes implies an epidemic of type 2 diabetes. Diabetes is associated with hyperglycemia-specific microvascular complications. Furthermore, macrovascular complications, especially coronary artery disease (CAD) but also stroke and peripheral vascular disease, are increased by two- to fourfold in type 2 diabetes. Cardiovascular disease (CVD) is the most important long-term complication and by far the greatest cause of death in people with diabetes. In fact, over 50% of all patients with type 2 diabetes die of CAD (1). Although much of the excess risk of CAD among patients with diabetes is accounted for by the presence of diabetes-associated CVD risk factors such as LDL cholesterol, elevated blood pressure, and smoking, a substantial proportion remains unexplained. A deleterious effect of the diabetic state on vascular and endothelial function is likely to be important via its ability to increase the potential for vasoconstriction and thrombosis. In population-based studies, the relationship of hyperglycemia to CAD is evident but the association is less strong than that of LDL cholesterol and elevated blood pressure. There is also evidence that the role of hyperglycemia with respect to the risk of CVD is larger among patients with type 1 diabetes than in patients with type 2 diabetes. In our study, an increment of 1 unit (%) of glycated hemoglobin increased CVD mortality by 52.5% (95% CI 28.4–81.3) in patients with type 1 diabetes and by 7.5% (4.3–10.8) in patients with type 2 diabetes (2). CAD also includes a microvascular component. Diabetic cardiomyopathy, a relatively rare condition, associates with the presence of microvascular complications in diabetes. Therefore, changes in small arteries …

Can Conventional Risk Factors Explain Excess Coronary Artery Disease Risk in South Asians: Dyslipidemias and Dysfunctional High Density Lipoprotein (HDL)

Over the past several years, the overall prevalence and incidence of cardiovascular diseases in general and coronary artery diseases (CAD) in particular have declined in the United States (US). However, among South Asian in general and South Asian immigrants in particular, a disturbing trend toward high rates of CAD has been noted. This trend is associated with a high prevalence of conventional risk factors and metabolic syndrome in this population, yet these conventional risk factors may not account for the greater CAD risk among SAIs. A search for additional markers is war- ranted, to enable early detection and prevention of CAD in this high risk group. High density lipoprotein (HDL) is one of the predictor of CAD and is considered to be cardio-protective. However, some of the recent studies have shown that HDL is not only ineffective as an antioxidant but, paradoxically, appears to be pro-oxidant, and has been found to be asso- ciated with CAD. Such HDL is called dysfunctional HDL. More research is required in South Asians to explore associa- tions with CAD and to enhance early detection and prevention of CAD in this high risk group. We present here an over- view on risk factors of CAD in general and dyslipidemias in particular in South Asians. In addition, concepts on dysfunc- tional HDL and its impact on CAD are also presented. At the end, recommendations are made to improve and prevent CAD morbidity and mortality in the South Asian communities. The high rates of CAD among South Asian immigrants are not limited to the United States and appear to be part of a global phenomenon (10). Further, CAD risk factors are pre- sent in South Asians at a younger age compared to other populations, resulting in CAD at a younger age than in other populations (3). The reasons for early development of CAD risk factors at a relatively young age in South Asian immi- grants are still unclear.

Excess coronary artery disease risk in South Asian immigrants: can dysfunctional high-density lipoprotein explain increased risk?

Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the United States (US), and South Asian immigrants (SAIs) have a higher risk of CAD compared to Caucasians. Traditional risk factors may not completely explain high risk, and some of the unknown risk factors need to be explored. This short review is mainly focused on the possible role of dysfunctional high-density lipoprotein (HDL) in causing CAD and presents an overview of available literature on dysfunctional HDL. The conventional risk factors, insulin resistance parameters, and metabolic syndrome, although important in predicting CAD risk, may not sufficiently predict risk in SAIs. HDL has antioxidant, antiinflammatory, and antithrombotic properties that contribute to its function as an antiatherogenic agent. Recent Caucasian studies have shown HDL is not only ineffective as an antioxidant but, paradoxically, appears to be prooxidant, and has been found to be associated with CAD. Several causes have been hypothesized for HDL to become dysfunctional, including Apo lipoprotein A-I (Apo A-I) polymorphisms. New risk factors and markers like dysfunctional HDL and genetic polymorphisms may be associated with CAD. More research is required in SAIs to explore associations with CAD and to enhance early detection and prevention of CAD in this high risk group.

Can novel Apo A-I polymorphisms be responsible for low HDL in South Asian immigrants?

Coronary artery disease (CAD) is the leading cause of death in the world. Even though its rates have decreased worldwide over the past 30 years, event rates are still high in South Asians. South Asians are known to have low high-density lipoprotein (HDL) levels. The objective of this study was to identify Apolipoprotein A-I (Apo A-I) polymorphisms, the main protein component of HDL and explore its association with low HDL levels in South Asians. A pilot study on 30 South Asians was conducted and 12-h fasting samples for C-reactive protein, total cholesterol, HDL, low-density lipoprotein (LDL), triglycerides, Lipoprotein (a), Insulin, glucose levels, DNA extraction, and sequencing of Apo A-I gene were done. DNA sequencing revealed six novel Apo A-I single nucleotide polymorphisms (SNPs) in South Asians, one of which (rs 35293760, C938T) was significantly associated with low (<40 mg/dl) HDL levels (P = 0.004). The association was also seen with total cholesterol (P = 0.026) and LDL levels (P = 0.032). This pilot work has highlighted some of the gene-environment associations that could be responsible for low HDL and may be excess CAD in South Asians. Further larger studies are required to explore and uncover these associations that could be responsible for excess CAD risk in South Asians.

Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men

The objective of this study was to examine determinants of excess coronary artery disease risk in UK South Asians, more prevalent in this population than UK Caucasians, by examining differences in risk factors, vascular function, and endothelial progenitor cells (EPCs). 24 South Asian and 25 Caucasian healthy age-matched nonsmoking men were studied. Vascular function was assessed by flow-mediated and GTN brachial artery dilatation and blood flow responses to infusion of ACh, SNP, and L-NMMA. EPC number and function were measured by flow cytometry (CD34, CD133, and KDR positive cells), and CFU/migration assays. Traditional risk factors and anthropometric measurements were similar in the groups. South Asians had higher fasting insulin levels (6.01 versus 3.62 microU/mL; P = 0.02). South Asians had lower FMD (6.9 versus 8.5%; P = 0.003), L-NMMA response (0.8 versus 1.3 mL/min/100 mL; P = 0.03), mean SNP response (9.5+/-0.6 versus 11.6+/-0.6; P = 0.02), EPC number (0.046+/-0.005% versus 0.085+/-0.009%; P = < 0.001), and CFU ability (CFU 4.29+/-1.57 versus 18.86+/-4.00; P = 0.005). EPC number was the strongest predictor of FMD. Ethnicity was the strongest predictor of EPC number. Healthy South Asian men are more insulin resistant, and demonstrate endothelial dysfunction and reduced EPC number and function compared with Caucasians. These abnormalities may contribute to their increased CAD risk.

Measurement issues related to lipoprotein heterogeneity

In clinical practice, the coronary artery disease (CAD) risk associated with high levels of low-density lipoprotein (LDL) or low levels of high-density lipoprotein (HDL) is assessed not by measuring LDL and HDL particles directly, but by measuring the amount of cholesterol carried by these lipoproteins. It is not generally appreciated how much the amount of cholesterol per particle varies from person to person, especially for LDL, because of differences in the relative amounts of cholesterol ester and triglycerides in the particle core as well as differences in particle diameter. As a consequence of the magnitude and prevalence of this lipid compositional variability, even the most accurate lipoprotein cholesterol measurements will, for many individuals, provide an inaccurate measure of the number of circulating lipoprotein particles and the CAD risk they confer. Nuclear magnetic resonance (NMR) spectroscopy offers an efficient new means of measuring lipoprotein levels in plasma, with quantification based not on cholesterol content, but on the amplitudes of spectral signals emitted by lipoprotein subclasses of different size. Because the subclass signal amplitudes are not influenced by cholesterol compositional variability, they provide a direct measure of lipoprotein particle concentrations. NMR data from the Framingham Offspring Study demonstrate a significant “disconnect” between LDL cholesterol and LDL particle concentrations in patients with low levels of HDL cholesterol. The results imply that a substantial portion of the excess CAD risk of patients with low HDL stems from an unrecognized excess of LDL particles containing less cholesterol than normal. Patients with this abnormality would benefit from LDL-lowering therapy but are not identified as candidates for such treatment on the basis of traditional LDL cholesterol tests.

Cigarette Smoking-Associated Changes in Blood Lipid and Lipoprotein Levels in the 8-to 19-Year-Old Age Group: A Meta-Analysis

In this meta-analysis it was demonstrated that, when compared with nonsmokers of similar age, smokers in the 8- to 19-year-old age group have significantly higher serum levels of triglyceride (+11.8%), very-low-density lipoprotein (VLDL)-cholesterol (+12.4%) and low-density lipoprotein (LDL)-cholesterol (+4.1%) and significantly lower serum levels of high-density lipoprotein (HDL)-cholesterol (-8.5%) and total cholesterol (-3.7%). All of these smoking-associated changes are in the same direction as those found in adults, with the exception of total cholesterol levels, which are significantly increased in adult smokers. The extent to which mean triglyceride, LDL-cholesterol, and HDL-cholesterol levels are shifted is significantly greater in the 8- to 19-year-old smokers than in adult smokers. The changes in mean total cholesterol levels among smokers in both age groups represent only the net shifts in the lipoprotein fractions and are therefore likely to be a less sensitive indicator of the possible lipid-related excess coronary artery disease risk in smokers.