Association of obesity, diabetes, and hypertension with arsenic in drinking water in the Comarca Lagunera province (north-central Mexico).

Chronic endemic regional hydroarsenicism (CERHA) is a global issue that affects over 200 million people exposed to arsenic (As) in drinking water. This includes 1.75 million individuals residing in La Comarca Lagunera, a region in north-central Mexico. Arsenic levels in this region typically exceeds the WHO guideline of 10 µg L-1. Biochemical alterations related to the human As metabolism may increase the risk of overweight and obesity (O&O), type 2 diabetes (T2D), and hypertension (AHT). In our study, we investigated the role of As in drinking water as a risk factor for these metabolic diseases. We focused on populations with historically moderate (San Pedro) and low (Lerdo) drinking water As levels and people with no historical evidence of As water contamination. The exposure assessment to As was based on measurements of the drinking water (medians 67.2, 21.0, 4.3 µg L-1) and urinary As concentrations in women (9.4, 5.3, 0.8 µg L-1) and men (18.1, 4.8, 1.0 µg L-1). A significant correlation between As in drinking water and urine evidenced the As exposure in the population (R2 = 0.72). Adjusted odds ratios with 95% confidence intervals evidenced higher chances of being diagnosed with T2D (1.7, 1.2-2.0) and AHT (1.8, 1.7-1.9) in individuals living in San Pedro than those in Lerdo. Still, there was no significant association with obesity. Individuals living in CERHA towns were found to have a higher risk of obesity (1.3-1.9), T2D (1.5 to 3.3), and AHT (1.4 to 2.4) compared to those residing in non-CERHA towns. Finally, obesity is more probable in women [inverse of OR and 95%CI 0.4 (0.2-0.7)] compared to men, while men is more likely to be diagnosed with T2D [OR = 2.0 (1.4-2.3)] and AHT [OR = 2.0 (1.5-2.3)] than women, independently of the municipality.

Timing of complementary food introduction and age at diagnosis of type 1 diabetes: the SEARCH nutrition ancillary study (SNAS).

The association between timing of complementary food introduction and age at diagnosis of type 1 diabetes was investigated among 1077 children in the SEARCH for Diabetes in Youth study. Age at diagnosis was 5 months earlier for children introduced to sugar-sweetened beverages (SSB) in the first 12 months of life compared with those who were not (9.0±0.2 vs 9.5±0.1; P=0.02) independent of human leukocyte antigen (HLA) risk status. Analyses stratified by HLA risk status found that children with a high-risk HLA genotype had an earlier age at diagnosis if they were introduced to fruit juice in the first year of life (mean age at diagnosis=9.3±0.1, 9.1±0.1 and 9.6±0.2 for introduction at ⩽6 months, between 7 and 11 months and ⩾12 months, respectively; P=0.04). Introduction of SSB in the first year of life may accelerate the onset of type 1 diabetes independent of HLA risk status.

Diabetic retinopathy in the SEARCH for Diabetes in Youth Cohort: a pilot study.

AIMS: The aim of this pilot study was to generate an initial estimate of the prevalence and correlates of diabetic retinopathy in a racially and ethnically diverse sample of youth with Type 1 and Type 2 diabetes mellitus. METHODS: A pilot study was conducted among 222 individuals with Type 1 diabetes (79% non-Hispanic white, 21% other) and 43 with Type 2 diabetes (28% non-Hispanic white, 72% other), all of > 5 years duration (mean duration 6.8 years) who participated in the SEARCH for Diabetes in Youth study. Diabetic retinopathy was assessed using non-mydriatic retinal photography of both eyes. RESULTS: The prevalence of diabetic retinopathy was 17% for Type 1 diabetes and 42% for Type 2 diabetes (odds ratio 1.50, 95% CI 0.58-3.88; P = 0.40 adjusted for age, duration, gender, race/ethnicity, parental education and HbA(1c). HbA(1c) was significantly higher among those with any diabetic retinopathy (adjusted mean 79 mmol/mol, 9.4%) vs. no diabetic retinopathy (adjusted mean 70 mmol/mol, 8.6%) (P = 0.015). LDL cholesterol was also significantly higher among those with any diabetic retinopathy (adjusted mean 107.2 mg/dl) compared with those without diabetic retinopathy (adjusted mean 97.9 mg/dl) (P = 0.04). CONCLUSIONS: The prevalence of diabetic retinopathy in contemporary young individuals was substantial, particularly among minority youth and those with Type 2 diabetes. Further long-term study of diabetic retinopathy in youth is needed.

Sex-specific genetic architecture of human fatness in Chinese: the SAPPHIRe Study.

To dissect the genetic architecture of sexual dimorphism in obesity-related traits, we evaluated the sex-genotype interaction, sex-specific heritability and genome-wide linkages for seven measurements related to obesity. A total of 1,365 non-diabetic Chinese subjects from the family study of the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance were used to search for quantitative trait loci (QTLs) responsible for the obesity-related traits. Pleiotropy and co-incidence effects from the QTLs were also examined using the bivariate linkage approach. We found that sex-specific differences in heritability and the genotype-sex interaction effects were substantially significant for most of these traits. Several QTLs with strong linkage evidence were identified after incorporating genotype by sex (G × S) interactions into the linkage mapping, including one QTL for hip circumference [maximum LOD score (MLS) = 4.22, empirical p = 0.000033] and two QTLs: for BMI on chromosome 12q with MLS 3.37 (empirical p = 0.0043) and 3.10 (empirical p = 0.0054). Sex-specific analyses demonstrated that these linkage signals all resulted from females rather than males. Most of these QTLs for obesity-related traits replicated the findings in other ethnic groups. Bivariate linkage analyses showed several obesity traits were influenced by a common set of QTLs. All regions with linkage signals were observed in one gender, but not in the whole sample, suggesting the genetic architecture of obesity-related traits does differ by gender. These findings are useful for further identification of the liability genes for these phenotypes through candidate genes or genome-wide association analysis.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Diagnosis of insulin resistance in hypertensive patients by the metabolic syndrome: AHA vs. IDF definitions.

BACKGROUND: Subjects with the metabolic syndrome are accompanied by insulin resistance (IR). However, it is not clear how well the newly defined metabolic syndrome identifies IR specifically in hypertensive subjects. AIMS: The purpose of the study was to evaluate the performance of the metabolic syndrome, defined by the American Heart Association (AHA) and the International Diabetes Federation (IDF) definitions, in identifying IR in hypertension. METHODS: The analysis is a cross-sectional study. Totally, 228 hypertensive patients and 92 non-diabetic normotensive controls who received insulin suppressive tests for direct evaluation of their insulin sensitivity were included from the Stanford Asia and Pacific Program for Hypertension and IR. McNemar's tests were used to compare sensitivity and specificity of the AHA-defined with the IDF-defined metabolic syndrome in diagnosis of IR. RESULTS: The sensitivity of the metabolic syndrome for IR in hypertension was 89.7% and the specificity 45.9% by the AHA definition. Using the IDF definition, the sensitivity was 77.6%, and the specificity increased to 63.5%. The diagnostic power of individual components of the syndrome was also modest. The predictive discrimination of wider waist circumference was similar to that of the AHA-defined metabolic syndrome. CONCLUSIONS: Use of the metabolic syndrome by the AHA definition provided good sensitivity, but low specificity to diagnose IR in hypertension. The IDF definition improved in false-positive rate, but it was still not specific enough to identify IR in hypertension.

Serum estradiol and risk of stroke in elderly men.

OBJECTIVE: To determine if levels of serum estradiol and testosterone can predict stroke in a population-based sample of elderly men. METHODS: Serum 17beta estradiol and testosterone were measured in 2,197 men aged 71 to 93 years who participated in the Honolulu-Asia Aging Study from 1991 to 1993. All were free of prevalent stroke, coronary heart disease, and cancer. Participants were followed to the end of 1998 for thromboembolic and hemorrhagic events. RESULTS: During the course of follow-up, 124 men developed a stroke (9.1/1,000 person-years). After age adjustment, men in the top quintile of serum estradiol (> or =125 pmol/L [34.1 pg/mL]) experienced a twofold excess risk of stroke vs men whose estradiol levels were lower (14.8 vs 7.3/1,000 person-years, p < 0.001). Among the lower quintiles, there were little differences in the risk of stroke. Findings were also significant and comparable for bioavailable estradiol and for thromboembolic and hemorrhagic events. After additional adjustment for hypertension, diabetes, adiposity, cholesterol concentrations, atrial fibrillation, and other characteristics, men in the top quintile of serum estradiol continued to have a higher risk of stroke vs those whose estradiol levels were lower (relative hazards = 2.2; 95% CI = 1.5 to 3.4, p < 0.001). Testosterone was not related to the risk of stroke. CONCLUSIONS: High levels of serum estradiol may be associated with an elevated risk of stroke in elderly men.

Insulin resistance and weight gain in postmenopausal women of diverse ethnic groups.

OBJECTIVE: This study was conducted to examine the influence of insulin resistance on weight change in postmenopausal women of various ethnic groups. SUBJECTS: Data were obtained from 3389 women (60% White, 20% Black, 12% Hispanic, and 8% Asian/Pacific Islander), ages 50-79, enrolled in either the Women's Health Initiative Clinical trial or Observational Study, whose blood samples were selected randomly from the full cohort of 161 809 women for analyses. MEASUREMENTS: Glucose, insulin, and lipids were measured on fasting serum samples drawn at baseline and after 3 y of follow-up. Weight, height, waist circumference, and blood pressure were measured. Physical activity and energy intake were assessed via questionnaire. Insulin resistance was estimated using the HOMA (homeostasis model) calculation. RESULTS: Average age was 62 y, average BMI (body mass index) was 27.4 kg/m2, and average weight change was a gain of 0.4 kg in 3 y. In a multivariate analysis, insulin resistance and insulin concentrations were independent predictors of increases in weight in White women (P=0.002 and 0.004, respectively) and in the combined group (P=0.027 and 0.039). For the whole group, after adjustment for other covariates, those in the highest quartile of insulin resistance gained 0.4 kg in 3 y, whereas those in the lowest quartile lost 0.06 kg. Similar trends were found for insulin resistance and weight gain in Hispanic and Asian/Pacific Islander women, but they did not reach statistical significance. In Black women, no relation was seen between either insulin or insulin resistance and weight change. A significant interaction between obesity and insulin resistance was observed (P=0.002 for White women and 0.032 for the whole group), so that there is weight gain with increasing insulin resistance in the leaner women, but weight loss with increasing insulin resistance in the most obese. CONCLUSION: Insulin resistance appears to be a predictor of weight gain in postmenopausal women, except for the most obese women. The effect is more pronounced in women who have a lower BMI, and the effect was not seen in the Black women who as a group had a higher BMI.

A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly.

High density lipoprotein cholesterol (HDL-C) levels are inversely associated with the incidence of coronary heart disease (CHD) in middle-aged individuals; in the elderly, the association is less clear. Genetic factors, including variations in the cholesteryl ester transfer protein (CETP) gene, play a role in determining HDL-C levels. Controversy remains about whether CETP deficiency and the resultant rise in HDL-C are antiatherogenic, or whether CETP has the opposite effect due to its role in reverse cholesterol transport. In a seven-year follow-up of 2340 men aged 71-93 in the Honolulu Heart Program, the age-adjusted CHD incidence rates were significantly lower in men with high versus low HDL-C levels. After adjustment for age, hypertension, smoking, and total cholesterol, the relative risk of CHD for those with HDL-C levels >or=60 mg/dl, compared with those with HDL-C levels <40 mg/dl, was 0.6. Men with a CETP mutation had the lowest rates of CHD, although this was not statistically significant. These data indicate that HDL-C remains an important risk factor for CHD in the elderly. Whether a CETP mutation offers additional protection against CHD warrants further investigation.

Production and characterization of monoclonal antibodies to E1 Tor toxin co-regulated pilus of Vibrio cholerae.

Murine monoclonal antibodies (MAbs) against Vibrio cholerae toxin co-regulated pilus (TCP) were generated using conventional hybridoma procedures. Four hybridomas were obtained and two characterized. Hybridomas 10E10E1 and 4D6F9 secreted antibodies of the IgG2a and IgG1 isotypes, respectively, that reacted with a 24-kDa antigen corresponding to the product of the El Tor tcpA gene fused to a six Histidine tail. Additionally, MAbs produced by 4D6F9 selectively recognized the major pilin subunit (TcpA) of El Tor and O139 vibrios in western immunoblot, while MAbs from 10E10E1 also cross-reacted with classical TcpA. Furthermore, vibrios expressing TCP on their surface selectively inhibited binding of the antibodies secreted by both hybridomas to TcpA-coated microtiter plates. Thus, the MAbs reported in this work detected the structural subunit of the pilus either denatured or assembled on the bacterial surface.

A "natural experiment" in cardiovascular epidemiology in the early 21st century.

Despite similar traditional risk factors, morbidity and mortality rates from coronary heart disease in western and non-western cohorts remain substantially different. Careful study of such cohorts may help identify novel risk factors for CHD, and contribute to the formulation of new preventive strategies

Relationship between plasma glucose concentrations and Native Hawaiian Ancestry: The Native Hawaiian Health Research Project.

OBJECTIVE: To investigate the relationship between fasting glucose and 2 h glucose with percentage of Hawaiian ancestry and ethnic admixture. DESIGN: Cross-sectional epidemiological study of type 2 diabetes and heart disease risk factor prevalence among Native Hawaiians. SUBJECTS: A total of 578 Native Hawaiians residing in two rural communities were examined between 1993 and 1996. Sample sizes in statistical analyses varied due to missing data and selection criteria based on ethnic ancestry. MEASUREMENTS: Percentage of Hawaiian ancestry and non-Hawaiian ethnic admixture, assessed by self-report. Fasting and 2 h post glucose challenge plasma glucose levels. Anthropometric measures (height, weight, waist and hip circumferences). Self-report of diet and physical activity. Medical history. RESULTS: Increased Hawaiian blood quantum was significantly associated with increased fasting glucose (P=0.0047), increased body mass index (BMI; P<0.0001), waist-to-hip ratio (WHR; P=0.0103), and age (P<0.0001), but not with leisure time physical activity and total dietary caloric intake. This association was attenuated after adjusting for BMI and WHR, but not by age-adjustment alone. However, when the effects of descent from other ethnic groups was examined in a subset of participants, full-Hawaiians had significantly higher fasting glucose concentrations (7.28 mmol/l) than part-Hawaiians after adjustments for age, gender, BMI and WHR. In contrast, part-Hawaiians of predominantly Asian ancestry had the highest 2 h glucose concentrations (7.62 mmol/l). CONCLUSION: These results suggest that ethnic admixture may be an important, but extremely complex, factor concerning the high prevalence of type 2 diabetes observed among this population. The complexity of this relationship may have obscured the relationship between ancestry and glucose tolerance in earlier observations of this population.

Ankle-brachial blood pressure in elderly men and the risk of stroke: the Honolulu Heart Program.

Although low ankle/brachial blood pressure index (ABI) is a marker of generalized atherosclerosis in the elderly, it has not been identified as a risk factor for stroke. The purpose of this report is to examine the relation between ABI and stroke in elderly men. ABI was measured from 1991 to 1993 in 2767 men aged 71 to 93 years in the Honolulu Heart Program without a history of stroke and coronary heart disease. Subjects were followed for 3 to 6 years for fatal and nonfatal thromboembolic and hemorrhagic stroke. During follow-up, there were 91 strokes. There was an age-adjusted 2-fold excess in men with an ABI < 0.9 (6.0%) versus men with an ABI > or = 0.9 (2.9%, P < 0.01). Thromboembolic events occurred in 4.6% of men with an ABI < 0.9 and in 2.0% in those with an ABI > or = 0.9 (P < 0.01). Hemorrhagic stroke was also more frequent in men with a low ABI (< 0.9) versus a higher ABI (1.9 vs. 0.8%, respectively). After adjusting for other factors, the risk of total and thromboembolic strokes increased with declining ABI (P = 0.019 and P = 0.004, respectively). The relation between ABI and stroke was similar and statistically significant in the presence and absence of diabetes and hypertension (P < 0.05). Findings suggest that ABI is inversely related to the incidence of stroke. Simple measurement of ABI in an outpatient setting could be an important tool for assessing the risk of stroke in the elderly.

Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study.

BACKGROUND: A generally held belief is that cholesterol concentrations should be kept low to lessen the risk of cardiovascular disease. However, studies of the relation between serum cholesterol and all-cause mortality in elderly people have shown contrasting results. To investigate these discrepancies, we did a longitudinal assessment of changes in both lipid and serum cholesterol concentrations over 20 years, and compared them with mortality. METHODS: Lipid and serum cholesterol concentrations were measured in 3572 Japanese/American men (aged 71-93 years) as part of the Honolulu Heart Program. We compared changes in these concentrations over 20 years with all-cause mortality using three different Cox proportional hazards models. FINDINGS: Mean cholesterol fell significantly with increasing age. Age-adjusted mortality rates were 68.3, 48.9, 41.1, and 43.3 for the first to fourth quartiles of cholesterol concentrations, respectively. Relative risks for mortality were 0.72 (95% CI 0.60-0.87), 0.60 (0.49-0.74), and 0.65 (0.53-0.80), in the second, third, and fourth quartiles, respectively, with quartile 1 as reference. A Cox proportional hazard model assessed changes in cholesterol concentrations between examinations three and four. Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1.64, 95% CI 1.13-2.36). INTERPRETATION: We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4.65 mmol/L) in elderly people.

The relationship of psychosocial factors to total mortality among older Japanese-American men: the Honolulu Heart Program.

OBJECTIVE: To examine the predictive value of psychosocial factors as risk factors for all-cause mortality. DESIGN: A community-based longitudinal cohort study: The Honolulu Heart Program. SETTING: Population-based study conducted in Oahu, Hawaii. PARTICIPANTS: Three thousand four hundred and ninety-seven men age 71 to 93 were examined and followed prospectively for all-cause mortality for an average of 6 years. MEASUREMENTS: Psychosocial data were obtained using the Lubben Social Networks Scale (LSNS). The LSNS consists of 10 items-family relationships (three items), relationships with friends (three items), and interdependent social supports and living arrangements (four items). We divided the LSNS score into quartiles for comparison, with the first quartile representing the lowest social support and the fourth quartile representing the highest social support. RESULTS: A significant dose-response relationship was noted with LSNS score and total mortality: 33.8% in the first quartile died over the follow-up period, 23.4% in the second, 18% in the third, and 15.7% in the fourth (P < .001). Six-year age-adjusted mortality rates were 66.2, 45.7, 37.8, and 33.7 per 1,000 person years in the first, second, third, and fourth, respectively (P < .001). Using age-adjusted Cox proportional hazards models, with the first quartile of LSNS as the reference group, relative risk for mortality was 0.69 (95% confidence interval (CI) = 0.58-0.82), 0.57 (95% CI = 0.47-0.70), and 0.52 (95% CI = 0.43-0.64) in the second, third, and fourth quartiles, respectively. Cox models were repeated, controlling for age and smoking status, and low LSNS scores remained significantly associated with higher mortality (P = .0001). CONCLUSIONS: Our findings suggest that social networks were significantly independently associated with 6-year all-cause mortality in this cohort of older Japanese-American men. Social interventions in old age may reduce early mortality.

Plasma fibrinogen as a predictor of total and cause-specific mortality in elderly Japanese-American men.

The relation between plasma fibrinogen and total and cause-specific mortality was investigated in a cohort of 3571 Japanese-American men aged 71 to 93 years during a median follow-up of 4.4 years. There were a total of 728 deaths, of which 37% were accounted for by cardiovascular disease and 27% by cancer. The age-adjusted relative risk (RR) for total mortality in the top quintile of fibrinogen (>3.51 g/L) compared with the bottom quintile (<2.57 g/L) was 4.3 (P<0.0001) in the first year of follow-up. RR was reduced to 1.7 in the second year but remained significantly and slightly increased in subsequent years. After adjustment for age and confounding risk factors, the RRs (and 95% confidence intervals) associated with a 1-SD increment of fibrinogen (0.64 g/L) for all-cause, cardiovascular disease, cancer, and other-cause mortality were 1.3 (1.2 to 1.4), 1.2 (1.1 to 1.4), 1.3 (1.2 to 1.5), and 1.3 (1.2 to 1.5), respectively. Preexisting diseases did not influence the significant association of fibrinogen with mortality. There was a significant interaction of fibrinogen with white blood cell count but not with cigarette smoking. We conclude that plasma fibrinogen is an independent risk factor for mortality from a broad spectrum of diseases in elderly men and that this universal effect of fibrinogen on mortality may be mediated partly through inflammation.

Differential interleukin-8 response of intestinal epithelial cell line to reactogenic and nonreactogenic candidate vaccine strains of Vibrio cholerae.

In this study, we analyzed whether attachment of Vibrio cholerae vaccine strains to human intestinal epithelial cells can induce an interleukin-8 (IL-8) response. The IL-8 transcripts were detected by PCR amplification of reverse-transcribed mRNA, and the gene product secretion was measured by an enzyme-linked immunosorbent assay. Infection of monolayers of the undifferentiated HT29-18N2 cell line with reactogenic (JBK70 and 81) and nonreactogenic (CVD103HgR and 638) vaccine strains of V. cholerae resulted in markedly higher IL-8 expression by epithelial cells exposed to reactogenic strains than by cells exposed to the nonreactogenic strains. Additionally, epithelial cells produced IL-8 transcripts following stimulation with cholera vaccine strains in a concentration-dependent manner. These results represent a new insight into the inflammatory component of reactogenicity and could be used as a predictive marker of vaccine reactogenicity prior to human testing.

Apolipoprotein A-1 predicts coronary heart disease only at low concentrations of high-density lipoprotein cholesterol: an epidemiological study of Japanese-Americans.

Conventional epidemiological and clinical studies of apolipoprotein A-1 and high-density lipoprotein-cholesterol have demonstrated, when examined jointly, that high-density lipoprotein is a better predictor of coronary heart disease. This strategy does not take into account known lipid metabolic relationships. A statistical approach that takes into account apolipoprotein A-1 being a constituent of the high-density lipoprotein particle is more appropriate. Among 1,177 Japanese-American men of the Honolulu Heart Program cohort free of disease at baseline (1980-1982), 182 new coronary heart disease cases developed over a 12-year follow-up period. After removing the linear relationship with high-density lipoprotein-cholesterol, a relative measure of apoliprotein A-1 concentration was derived. Based on joint conditions of "low" and "high" relative apoliprotein A-1 concentration and < or =40 and >40 mg/dl for the high-density lipoprotein-cholesterol distribution, four groupings were created. Among relative joint groupings of high/< or =40, low/< or =40, high/>40, and low/>40, respectively, the 12-year coronary heart disease incidence varied from 28.6, 18.2, 8.3, to 11.7 cases per 1,000 person-years. A test of statistical interaction was significant (P=0.028). Additional analyses revealed coronary heart disease cases were more likely among men with triglycerides > 190 mg/dl. Observed patterns of relationships among relative apoliprotein A-1 level, high-density lipoprotein cholesterol, and triglycerides with incident coronary heart disease are consistent with patterns noted in clinical, laboratory, and transgenic animal research more capable of elucidating mechanisms of disease causation. This epidemiological study suggests similar mechanisms may be operating at a population level, and may contribute to the public health burden of coronary heart disease.

Low-density lipoprotein particle size, triglycerides, and high-density lipoprotein cholesterol as risk factors for coronary heart disease in older Japanese-American men.

Decreased low-density lipoprotein (LDL) particle size is associated with coronary heart disease (CHD) risk among middle-aged Caucasian populations, and has been consistently correlated with increased plasma levels of triglyceride and decreased levels of high-density lipoprotein (HDL) cholesterol. This study examines whether these risk factors predict CHD among older Japanese-American men. With use of the Honolulu Heart Program Lipoprotein Exam 3 (1980 to 1982) as baseline, and 12-year follow-up for CHD events, a nested, case-control study was designed. One hundred forty-five incident CHD cases were identified and matched to 2 controls each. LDL particle diameter (size) was determined by gradient gel electrophoresis. A 10-angstrom (A) decrease in LDL size at baseline was associated with increased risk of incident CHD (relative risk 1.28, 95% confidence interval 1.01 to 1.63). After adjustment for baseline risk factors, the LDL size association was no longer statistically significant (relative risk 1.13, 95% confidence interval 0.86 to 1.49). When principal components analysis was used to define a composite variable for LDL size, triglycerides, and HDL cholesterol, this component predicted CHD independent of smoking, alcohol consumption, physical activity, body mass index, hypertension, diabetes, and beta-blocker use (p <0.01). Therefore, this prospective analysis of data from older, Japanese-American men demonstrated that decreased LDL size is a univariate predictor of incident CHD, and that a composite risk factor of LDL size, triglyceride, and HDL cholesterol was a risk factor for CHD independent of other risk factors.