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For several decades we have studied health outcomes in identified Asian American (ASAM) ethnic groups, comparing ASAM subgroups to whites and to each other. The most striking disparities we found involved South Asians (SAs). The SA individuals had higher coronary artery disease (CAD) risk and lower cancer risk than whites or any other ASAM group. The SA individuals also did not share the lower venous thromboembolism risk of all other ASAM groups. The relatively low prevalence of CAD risk traits in SAs with high CAD incidence defines a paradox. Exploration of these data might help the search for therapeutic and preventive medical benefits.

Background: Reports suggest a higher risk of venous thromboembolism (VTE) in Black persons compared to Whites. The major clinical presentations of VTE, pulmonary embolism (PE) and deep venous thrombosis (DVT) are considered parts of the same pathological process and generally share the same risk factors. Sparse data raise the possibility of additional Black/White disparity in clinical VTE presentation; specifically, larger proportions of presentation with PE in Blacks than Whites and vice versa with DVT in Whites compared to Blacks. We present here relevant data from a new study with 4,674 VTE subjects. Hypothesis: The Black/White disparity in VTE may be concentrated in greater risk of Blacks for PE. Methods: We studied composite VTE risk in 61,459 members of a comprehensive health plan, who had supplied self-classified ethnicity data on prior health examinations between 1978 and 1985 and remained plan members in 1996, when out-patient diagnoses were added to electronic health records. Subjects were 28% Black, (n = 17,442), and 53% White (n = 32,557). From 1996 through 2015, at least one diagnosis of VTE was made during an outpatient visit or hospitalization for 4,675 persons (1,554 Black and 2,576 White). With Whites as referent we performed logistic regressions with 5 covariates. Models stratified by race were performed to explore traits of specific VTE codes and circumstances of diagnosis (hospitalization, out-patient, etc.). Results: The table shows HRs (95% CI) of Blacks vs Whites. Increased VTE risk of Blacks in each sex was entirely concentrated in subjects with PE and with hospitalization diagnoses. Among covariates sex, education, and smoking were unrelated to VTE risk while BMI was directly associated; results were similar in Whites, Blacks and race-stratified models within the diagnosis code and location of diagnosis groups. Conclusion: Compared to Whites, Black persons have an unexplained increased risk of PE but not of DVT.

CONTEXT South Asians (ancestry in India, Pakistan, Bangladesh, or Sri Lanka) may have lower cancer risk than other racial-ethnic groups. OBJECTIVE To supplement published cohort data suggesting low cancer risk in South Asians. DESIGN Logistic regression models with 7 covariates to study cancer mortality through 2012 in 273,843 persons (1117 South Asians) with baseline examination data from 1964 to 1985. MAIN OUTCOME MEASURE Cancer mortality. RESULTS Through 2012, death was attributed to cancer in 28,031 persons, of which 1555 were Asians, including 32 South Asians. The all-Asian vs white adjusted odds ratio was 1.0, and the South Asian vs white odds ratio was 0.5 (p < 0.001). In separate regressions, South Asians were at lower risk than blacks, Chinese, Filipinos, Japanese, or other Asians. The South Asian-white disparity was concentrated in men but was generally similar when strata of smoking, body mass index, baseline age, and date of death were compared. CONCLUSION These data support the observation that compared with whites and other Asian groups, South Asians, especially men, have a lower risk of cancer.

Background: Several studies suggest a lower risk of venous thromboembolism (VTE) in Asians compared to other racial groups, and genetic mechanisms have been suspected. Despite their biological and cultural diversity, data have been sparse comparing risk of VTE among specific Asian ethnicities. Our previous report from 2000 on hospitalizations for VTEs in Asian Americans had included 337 subjects (all races) and numbers were insufficient to study specific Asian groups. We present here data from a new study with 4,674 VTE subjects. Hypothesis: Similar low VTE risk is present in multiple Asian ethnic groups. Methods: We studied composite VTE risk in 61,459 members of a comprehensive health plan, who had supplied self-classified ethnicity data on prior health examinations between 1978 and 1985 and had remained plan members in 1996, when outpatient diagnoses were added to computerized files. The subjects were 58% (n = 35,573) female and 42% (n= 25,886) male. From 1996 through 2015, at least one diagnosis of VTE was made during an outpatient visit or hospitalization for 4,675 persons. With Whites as the referent group, we performed logistic regressions controlled for age, sex, education, BMI, and smoking, yielding hazard ratios (HR) and 95% confidence intervals (CI). Results: The table shows HRs (CI) versus Whites (n=32,557) with 2,576 VTE. These lower HRs for VTE in Asians were generally similar in men and women. In the Asian stratum, a model with Chinese as referent showed an increased HR = 1.87 (1.09-3-21; p=0.02) for South Asians. Among covariates sex, education, and smoking were unrelated to VTE risk and BMI was positively associated; these results were similar in Whites, Blacks, and Asians. Conclusions: In conclusion, Chinese, Japanese, Filipinos and Other Asian Americans but not South Asians had substantially lower VTE risk compared to Whites. These data indirectly support a genetic explanation.

Lower risk of venous thromboembolism in Asians compared to Whites has been suggested. Despite the biological and cultural diversity of Asian Americans, data are sparse for specific ethnic groups. In our prior study of lower Asian American risk, the small number of subjects (337 in all races) precluded accurate study of specific Asian American groups. We present here a new study with 4674 venous thromboembolism subjects diagnosed between 1996 and 2015. Our study population was derived from 61,459 voluntary health examinees in a comprehensive northern California health plan with self-classified ethnicity: 53.0% Whites, 28.4% Blacks, 11.6% ASAMs, 6.8% Others. Of Asian Americans, 44.7% were Chinese, 32.8% Filipinos, 12.9% Japanese, 4.5% South Asians, and 5.0% Other Asians. Chinese, Japanese, Filipinos, and Other Asians each had lower venous thromboembolism risk than both Whites and South Asians, who had risk similar to each other. These data indirectly support a genetic explanation.

Context Controversy persists about optimal body weight. Many experts define "normal" (healthy) body mass index (BMI) as 18.5 to 24.9 kg/m2, 25 to 29.9 kg/m2 as overweight, and 30 kg/m2 or greater as obese. Obesity is subdivided into 30 to 34.9 kg/m2 (Grade 1), 35 to 39.9 kg/m2 (Grade 2), and 40 kg/m2 and above (Grade 3). Studies consistently show higher mortality for underweight and Grade 2 or 3 obesity, but results conflict for the overweight category and Grade 1 obesity. Objective To study 30-year risk of death related to baseline BMI. Design Retrospective cohort study in a multiracial population of 273,843 persons using logistic regression with 7 covariates (sex, age, race-ethnicity, education, marital status, smoking, alcohol intake). Main outcome measures Mortality risk by baseline BMI. Results With average follow-up exceeding 30 years, there were 103,218 deaths: 41,215 attributed to cardiovascular causes and 62,003 to noncardiovascular causes. Odds ratios (and 95% confidence intervals) for all deaths in BMI categories, with a BMI of 18.5 to 24.9 kg/m2 as the referent, were BMI below 18.5 kg/m2 = 1.1 (1.0-2.0), BMI 25 to 29 kg/m2 = 1.1 (1.1-1.2), BMI 30 to 34 kg/m2 = 1.5 (1.4-1.5), BMI 35 to 39 kg/m2 = 2.1 (1.9-2.3), and BMI 40 kg/m2 or higher = 2.7 (2.4-3.0). Disparities existed regarding age, race/ethnicity, cause of death, and interval to death. Conclusion Compared with persons with BMI defined as normal, persons who were underweight, overweight, and obese were at increased risk of death over 30 years.

Background Short QT syndrome (QTc ≤ 300 ms) is a novel hereditary channelopathy linked to syncope, paroxysmal atrial fibrillation, and sudden cardiac death. However, its epidemiological features remain unsettled. Objectives (1) To assess the prevalence of short QT in a large population-based sample; (2) to evaluate its demographic and clinical correlates and; (3) to determine its prognosis. Methods A database of 6.4 million electrocardiograms (ECGs) obtained between 1995 and 2008 among 1.7 million persons was used. An internal, population-based method for heart rate correction (QTcreg) was used and all ECGs with QTcreg ≤300 ms were manually validated. Linked health plan databases were used for covariate and survival ascertainment. Results Of 6,387,070 ECGs, 1086 had an ECG with machine-read QTcreg ≤300 ms. Only 4% (45/1086) were validated yielding a prevalence of 0.7 per 100,000 or 1 of 141,935 ECGs. At the person level, the overall prevalence of QTcreg ≤300 ms was 2.7 per 100,000 or 1 of 37,335. The factors independently and significantly associated with validated QTcreg ≤300 ms were age over 65 years, Black race, prior history of ventricular dysrhythmias, chronic obstructive pulmonary disease, ST-T abnormalities, ischemia, bigeminy pattern, and digitalis effect. After 8.3 years of median follow-up and relative to normal QTcreg, validated QTcreg ≤300 ms was associated after multivariate adjustment with a 2.6-fold (95% confidence interval [CI] = 1.9–3.7) increased risk of death. Conclusion QTcreg ≤300 ms was extraordinarily rare and was associated with significant ECG abnormalities and reduced survival.

There is compelling evidence that heavy alcohol drinking is related to increased risk of several cancer types, but the relationship of light–moderate drinking is less clear. We explored the role of inferred underreporting among light–moderate drinkers on the association between alcohol intake and cancer risk. In a cohort of 127,176 persons, we studied risk of any cancer, a composite of five alcohol-associated cancer types, and female breast cancer. Alcohol intake was reported at baseline health examinations, and 14,880 persons were subsequently diagnosed with cancer. Cox proportional hazard models were controlled for seven covariates. Based on other computer-stored information about alcohol habits, we stratified subjects into 18.4 % (23,363) suspected of underreporting, 46.5 % (59,173) not suspected of underreporting, and 35.1 % (44,640) of unsure underreporting status. Persons reporting light–moderate drinking had increased cancer risk in this cohort. For example, the hazard ratios (95 % confidence intervals) for risk of any cancer were 1.10 (1.04–1.17) at

OBJECTIVE To study risk factors for cell types of lung cancer. METHODS Cohort study of 126,293 persons with 1852 subjects with incident cancer. We performed Cox proportional hazards models (8 covariates) to estimate risk of the 4 most numerous specific cell types: adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and bronchioloalveolar carcinoma. RESULTS Smoking 1 or more cigarette packs per day was a powerful predictor (p < 0.0001) of all cell types, with hazard ratios ranging from 5.8 for bronchioloalveolar to 62.7 for squamous cell carcinoma. Other hazard ratio ranges included male/female from 0.6 (bronchioloalveolar, p < 0.05) to 2.0 (squamous, p < 0.001); black/white from 0.8 (small cell, p < 0.05) to 1.7 (squamous, p < 0.001); Asian/white from 0.8 (small cell) to 1.9 (bronchioloalveolar); and alcohol intake of 3 or more drinks per day from 1.0 (squamous) to 1.5 (adenocarcinoma, p < 0.01). College graduation and increasing body mass index were inversely related to risk of several cell types. Noteworthy sex-specific associations included increased risk of Asian vs white women for adenocarcinoma, squamous cell carcinoma and bronchioloalveolar carcinoma and substantially increased risk of adenocarcinoma in women with alcohol intake of 3 or more drinks per day. CONCLUSIONS These risk factor disparities for lung cancer cell types presumably reflect biologic differences. Future investigation may contribute to increased understanding of tumorigenesis and optimal treatment.

To supplement published cohort data about incident cancer in Asian Americans (Asians) including risk of specific Asian ethnic groups. A cohort study in 124,193 persons (13,344 Asians) with baseline examination data in 1978–1985 used Cox proportional hazards models with seven covariates to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Through 2012 cancer was diagnosed in 18,687 persons including 1,522 Asians. Compared to Whites, the HR (CIs) for any cancer in Asians was 0.8 (0.7–0.9, p

Population study data about relations of coffee drinking to arrhythmia are sparse.To study relations of coffee drinking to risk of cardiac arrhythmia in 130,054 persons with previous data about coffee habits.Design and Outcome Measure: We used Cox proportional hazards models with 8 covariates to study coffee-related risk in 3137 persons hospitalized for cardiac arrhythmia. We conducted a similar analysis of total caffeine-related risk in a subgroup with data about other caffeine intake (11,679 study participants; 198 hospitalized).With non-coffee-drinkers as the referent, the adjusted hazard ratio (HR) for any arrhythmia at the level of1 cup of coffee per day was 1.0 (95% confidence interval [CI] = 0.9-1.1; p = 0.7); for 1-3 cups/day, it was 0.9 (CI, 0.8-1.0; p = 0.2), and for ≥4 cups/day, it was 0.8 (CI, 0.7-0.9; p = 0.002). With coffee intake as a continuous variable, the HR per cup per day was 0.97 (CI, 0.95-0.99; p = 0.001). RESULTS were similar for several strata, including persons with history or symptoms of possible cardiore-spiratory disease and those without such history or symptoms. Coffee had similar relations to atrial fibrillation (48% of participants with arrhythmia) and most other specific arrhythmia diagnoses. Controlled for number of cups of coffee per day, total caffeine intake was inversely related to risk (HR highest quartile vs lowest = 0.6; p = 0.03).The inverse relations of coffee and caffeine intake to hospitalization for arrhythmias make it unlikely that moderate caffeine intake increases arrhythmia risk.

Purpose To identify ethnic differences for risk of hospitalization for asthma and chronic obstructive pulmonary disease (COPD). Methods We undertook a cohort study with 126,019 participants: 55% whites, 27% blacks, 11% Asians, and 4% Hispanics. To estimate asthma and COPD risk, we used Cox proportional hazards models adjusted for age, sex, body mass index, education, smoking, and alcohol intake. End points were hospitalizations for asthma or COPD. Results Compared with whites, relative risks (RR) with 95% confidence intervals (95% CI) for asthma among other groups were: blacks, 1.7 (1.4–2.0); Hispanics, 0.9 (0.6–1.4); and Asians, 1.6 (1.2–2.1). Among Asians, increased risk was concentrated in Filipino men and women and South Asian men. For COPD, whites were at highest risk; RR of blacks was 0.9 (0.7–1.0); Hispanics, 0.6 (0.3– 0.9); and Asians, 0.4 (0.3–0.6). COPD risk among Asians was lowest in Chinese with RR of 0.3 (0.1–0.5). Conclusions Ethnic disparities in risk of asthma and COPD as well as between both diseases exist, especially for Asian Americans, who have high asthma risk and low COPD risk. While residual confounding for smoking or other environmental factors could be partially responsible, genetic factors in Asians may be involved in decreased COPD risk.

Background: Limited data suggest that moderate alcohol drinkers may have better lung airways function than abstainers. Because few studies have fully accounted for confounders (including smoking and coronary disease), and some might have been biased by the inclusion with nondrinkers of alcohol drinkers who quit because of illness, we performed a cross-sectional analysis in a large free-living population. Methods: We studied the relation between alcohol and airways function in 177,721 members of a comprehensive health plan. An item on a questionnaire administered as part of a health examination asked for “usual number of drinks in the past year.” Respondents were asked to lump “wine, beer, whiskey, and cocktails” together. Health history queries included 47 items indicative of possible cardiorespiratory (CR) illness; participants with one or more positive response (61.0%) were classified as “CR yes.” Lung function measurements were part of the health examination; we studied one-second forced expiratory volume (FEV1), forced vital capacity (FVC), and FEV1/FVC by analysis of covariance and FEV1/FVC

Purpose Limited data suggest that alcohol drinking may have an inverse relation to risk of non-Hodgkin's lymphoma (NHL). Prospective data about alcohol, NHL, and other hematologic malignancies (HM) are sparse. Methods We carried out a cohort study in a multiethnic population of 126,293 adults who supplied baseline information at health examinations. There were subsequent HM diagnoses in 1244 persons. We used Cox proportional hazards models with seven covariates. The role of beverage types was studied by comparing groups with preponderant choices and by studying the role of frequency of drinking beverage types. Results Using lifelong abstainers plus infrequent drinkers as referent, adjusted relative risks (95% confidence intervals) for HM follow: less than one drink per day = 1.0 (0.9–1.2), one to two drinks per day = 0.9 (0.7–1.0), greater than three drinks per day = 0.7 (0.6–0.9, p = 0.008). For 673 NHL these were 1.2 (1.0–1.5), 0.9 (0.7–1.2), and 0.9 (0.6–1.2). Persons reporting greater than three drinks/day had inverse relations to lymphocytic (n = 146) and myelocytic (n = 169) leukemias, with relative risk of 0.5 (0.2–1.0, p

A paper showing that about one half of persons stating lifelong alcohol abstinence had previously reported drinking (Am J Epidemiol 2008; doi:10.1093/aje/kwn093) reopens debate about the validity of this frequently used referent group in alcohol-health studies. Misclassification of lifelong abstainers could result in underestimation of harmful effects of heavy drinking and overestimation of benefits of lighter drinking. Imprecise and unreliable ascertainment of alcohol intake is the rule in the area of alcohol epidemiology research. However, inaccurate ascertainment of past infrequent drinking may have less effect upon outcome estimates than the consequences of other measurement errors such as underreporting of intake. Communication about alcohol-health relations would be improved if all research reports explicitly described queries and methods by which alcohol intake was categorized and if limitations were always frankly acknowledged. Language: en

To evaluate further the relation between alcohol consumption and total mortality, we have carried out new Cox proportional hazards model analyses of 21,535 deaths through 2002 in the Kaiser Permanente study. This follow-up includes 2,618,523 person-years of observation, with a mean follow-up of 20.6 years. We adjusted for age, sex, ethnicity, body mass index, marital status, education, and smoking. New methodology was used to stratify light-moderate drinkers into groups felt more or less likely to include under-reporters. The analysis reconfirms that the relation of alcohol drinking to total mortality is J-shaped, with reduced risk (mainly because of less cardiovascular disease) for lighter drinkers and increased risk for persons reporting more than 3 drinks per day. Infrequent (occasional) drinkers have risk similar to that of lifelong abstainers, while former drinkers are at increased risk, especially for noncardiac death. The general shape of the relation of alcohol to mortality is similar for men and women. Age differences are substantial, with the apparent benefit from light-moderate drinking not seen before middle life. Our data indicate further that the apparent magnitude of benefit of lighter drinking is probably reduced by systematic underreporting.

Context: Heavy intake of alcoholic beverages is associated with an increased risk of developing several types of cancers at specific body sites. However, evidence is conflicting regarding alcohol-associated cancers in other sites of the body as well as the role played by choice of wine, liquor, or beer. Objective: To study incident cancer risk from 1978 to 1985 and through followup in 2012 relative to light-to-moderate and heavy drinking and to the choice of alcoholic beverage in a cohort of 124,193 persons. Design: Cohort. Main Outcome Measures: 1) Cox proportional hazards models controlled for 7 covariates to analyze alcohol-associated risk of any cancer and multiple specific types. 2) Similar analyses in strata of drinkers with or without a preponderant choice of wine, liquor, or beer and with or without inferred likelihood of underreporting. Results: With lifelong abstainers as referent, heavy drinking (≥ 3 drinks per day) was associated with increased risk of 5 cancer types: upper airway/digestive tract, lung, female breast, colorectal, and melanoma, with light-to-moderate drinking related to all but lung cancer. No significantly increased risk was seen for 12 other cancer sites: stomach, pancreas, liver, brain, thyroid, kidney, bladder, prostate, ovary, uterine body, cervix, and hematologic system. For all cancers combined there was a progressive relationship with all levels of alcohol drinking. These associations were largely independent of smoking, but among light-to-moderate drinkers there was evidence of confounding by inferred underreporting. Beverage choice played no major independent role. Conclusion: Heavy alcohol drinking is related to increased risk of some cancer types but not others. Because of probable confounding, the role of light-to-moderate drinking remains unclear. credits available for this article — see page 96.

A link exists between alcohol intake and increased blood pressure (BP), with many studies showing increased hypertension prevalence in heavy drinkers. The harmful and beneficial effects of alcohol can confound the study of the long-term risks of alcohol-related hypertension. We therefore studied cardiovascular sequelae separately in heavy drinkers, light drinkers, and abstainers among 127,212 subjects with BP and alcohol intake ascertained at 1978 to 1985 health examinations. Subsequent cardiovascular end points included mortality risk, hospitalization risk, and outpatient diagnosis of hypertension. Analyses were performed for all subjects and stratified by 5 alcohol-drinking categories (from never drinkers toor=3 drinks/day). With120/80 mm Hg as the referent, Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals for 3 higher BP categories (120 to 129/80 to 84, 130 to 139/85 to 89, andor=140/90 mm Hg). The covariates were age, gender, race, body mass index, education, and smoking. The risk of all outcomes was progressively higher for increasing BP categories, with a similarly increased risk for abstainers, light drinkers, and heavy drinkers. The interaction tests for alcohol and BP were not statistically significant for the mortality and hospitalization outcomes. Interpretation was limited by an inability to separate subjects with increased BP from alcohol consumption from those with other etiologies. In conclusion, the data indicate that the risks of hypertension are similar regardless of the amount of alcohol consumption.

Heavy alcohol drinking is associated with increased prevalence of systemic hypertension (HTN), but the relationship between moderate drinking and HTN remains unclear. We explored the possible role of underreporting among moderate drinkers.In a cross-sectional analysis of 105,378 persons, we defined a subset among persons reporting three or fewer drinks per day that was likely to include a disproportionate number of underreporters. This subset included persons who, on another occasion, indicated intake of three or more drinks per day or who ever had a diagnosis of an alcohol-related condition; these persons are called "positive." Persons who never reported three or more drinks per day and who had no alcohol-related diagnosis were called "negative." Logistic regression models estimated the odds ratios (ORs) for prevalent HTN (140/90 mm Hg or greater) in the positive and negative subgroups, compared with lifelong abstainers as referent. All persons and four race-gender groups were studied, and they were controlled for age, education, smoking, and body mass index. We also studied the relationship of blood liver transaminase enzyme levels in the positive and negative subgroups at specific alcohol intake strata.For persons reporting one to two drinks per day, the OR (95% confidence interval) of HTN was 1.32 (1.21-1.43) for positive persons and 1.16 (1.09-1.25) for negative persons. For those reporting less than one drink per day, the ORs were 0.97 (0.89-1.06) for positives and 0.92 (0.87-0.98) for negatives. For those reporting one to two drinks per day, positive/negative comparisons showed approximately a 75% increased prevalence of high liver transaminase enzymes. For those reporting less than one drink per day, the positive/negative difference was approximately 30%.In these data, increased prevalence of HTN among persons reporting one to two drinks per day appears to be partially due to underreporting of alcohol intake.

Myocardial damage from heavy alcohol intake can cause the heart failure (HF) syndrome, but the relation of lighter alcohol intake to HF has rarely been studied. We examined the risk of HF hospitalization among 126,236 subjects who supplied data about alcohol during health examinations from 1978 to 1985. Among 2,594 subjects who were subsequently hospitalized for HF, record review established an association between coronary artery disease (CAD) and HF (CAD-HF) in 1,559 patients. Among the remaining 1,035 subjects who had HF (non-CAD-HF), we attempted determination of preponderant etiologic and contributory factors. Analyses used Cox models that were controlled for 7 covariates, with usual alcohol intake studied categorically compared with that in subjects who did not drink alcohol. Heavier drinkers (or =3 drinks/day) but not light to moderate drinkers had increased risk of non-CAD-HF; e.g., relative risk for subjects who reportedor =6 drinks/day was 1.7 (95% confidence interval 1.1 to 2.6). This association of non-CAD-HF with heavy drinking was limited to subsets with cardiomyopathy or of unclear preponderant etiology. Alcohol drinking was inversely related to risk of CAD-HF (e.g., at 1 to 2 drinks/day, relative risk 0.6, 95% confidence interval 0.5 to 0.7), with consistency across subgroups of age, gender, ethnicity, education, smoking status, interval to diagnosis, and presence or absence of baseline heart disease or systemic hypertension. Moderate drinking was inversely related to non-CAD-HF only in subjects who had diabetes mellitus (n = 252). In conclusion, heavy, but not light, alcohol drinking is associated with increased risk of non-CAD-HF and that apparent protection by alcohol drinking against CAD-HF risk provides confirmation of a protective effect of alcohol against CAD.

The sparseness of prospective data about hemorrhagic stroke (HS) risk among Asian American ethnic groups led to the investigation of 128,934 persons with self-classified ethnicity at health examinations in 1978–1985. Subsequently, 431 persons were hospitalized for HS; 31% for subarachnoid hemorrhage (SAH) and 69% for intracerebral hemorrhage (ICH). Ethnic predictors of HS were studied by Cox proportional hazard models with 7 covariates. With whites as reference, the adjusted relative risk (95% CI) of all Asians for HS was 1.6 (1.1–2.3, p = 0.01), due substantially to increased risks of SAH in Japanese people and ICH in Filipinos. These data mandate emphasis upon preventive measures in these groups.

The substantial medical risks of heavy alcohol drinking as well as the probable existence of a less harmful or safe drinking limit have been evident for centuries. Modern epidemiology studies suggest lowered risk of morbidity and mortality among lighter drinkers. Thus, defining "heavy" drinking as > or =3 standard drinks per day, the alcohol-mortality relationship is a J-curve with risk highest for heavy drinkers, lowest for light drinkers and intermediate for abstainers. A number of non-cardiovascular and cardiovascular problems contribute to the increased mortality risk of heavier drinkers. The lower risk of light drinkers is due mostly to lower risk of the most common cardiovascular condition, coronary heart disease (CHD). These disparate relationships of alcoholic drinking to various cardiovascular and non-cardiovascular conditions constitute a modern concept of alcohol and health. Increased cardiovascular risks of heavy drinking include: (1) alcoholic cardiomyopathy, (2) systemic hypertension (high blood pressure), (3) heart rhythm disturbances, and (4) hemorrhagic stroke. Lighter drinking is not clearly related to increased risk of any cardiovascular condition and, in observational studies, is related to lower risk of CHD, ischemic stroke, and diabetes mellitus. A protective hypothesis for CHD is supported by evidence for plausible biological mechanisms attributable to ethyl alcohol. International comparisons and some prospective study data suggest that wine is more protective against CHD than liquor or beer. Possible non-alcohol beneficial components in wine (especially red) support possible extra protection by wine, but a healthier pattern of drinking or more favorable risk traits in wine drinkers may be involved.

PURPOSE: Little is known about the traits of decaffeinated coffee drinkers, who are sometimes used to ascertain whether the health effects of coffee intake are due to caffeine or some other coffee ingredient. METHODS: We studied these traits in 12,467 persons who reported type of coffee consumed at health examinations; 36% drank caffeinated only, 13% drank decaffeinated only, 27% drank both types and 24% drank no coffee. RESULTS: Odds ratios estimated from logistic regression analyses revealed that compared with regular (caffeinated) coffee drinkers or abstainers, decaffeinated coffee drinkers were less likely to be heavy coffee drinkers, smokers, alcohol drinkers, users of caffeinated soft drinks and medication and to be free of illness. Increased decaffeinated coffee drinking was associated with older age, female sex, African American ethnicity, use of special diets and cardiovascular, gastrointestinal, or neuropsychiatric symptoms. Persons on special diets were more likely to drink decaffeinated coffee whether they had heart disease or were free of any illness. CONCLUSION: These data suggest that decaffeinated coffee use is related to illness in some persons but to a healthy lifestyle in others. These potential and possibly conflicting confounding factors need to be considered when studying the health effects of coffee or caffeine.

Purpose To evaluate the effect of the consumption of caffeine-containing beverages on the risk of symptomatic liver cirrhosis (LC). Methods From 1994 to 1998, all the consecutive cirrhotic inpatients admitted in 19 collaborative hospitals for signs of liver decompensation in whom the diagnosis of liver cirrhosis was made for the first time (274 cases) and one or two gender, age, and place of residence pair matched individuals (458 controls) were recruited. Data on years of education, lifetime cigarette use, lifetime intake of alcohol- and caffeine-containing beverages, usual consumption of 180 food items, and on markers of hepatitis B and C viral infection were collected. Results A statistically significant trend toward lowered cirrhosis risk with increasing exposure to coffee was observed. The LC odds ratios decreased from 1.0 (reference category: lifetime abstainers from coffee) to 0.47 (95% confidence interval: 0.20, 1.10), 0.23 (0.10, 0.53), 0.21 (0.06, 0.74), and 0.16 (0.05, 0.50) in 1, 2, 3, and 4 or more cups of coffee drinkers, respectively. There was no convincing evidence that coffee consumption modifies the effects of the known risk factors of liver cirrhosis (alcohol intake and viruses infection). Conclusions These findings support the hypothesis that coffee, but not other beverages containing caffeine, may inhibit the onset of alcoholic and nonalcoholic liver cirrhosis.

This study assessed utilization of health services among 1317 adults referred to an outpatient Psychiatry Department alcohol treatment program from July, 1988 through December, 1989. The mean number of visits/year for 1 year before and 4 years after treatment referral were compared for all outpatient clinics combined and 4 clinic subgroups; the mean number of hospitalizations and number of days hospitalized were also analyzed. Overall, utilization was higher before treatment than after, except for Psychiatry Department visits. Amount of treatment received had little effect on utilization. These results suggest that alcoholism treatment contributes to a reduction in higher cost health services utilization. [Translations are provided in the International Abstracts Section of this issue.]

After decades of conflicting studies, the relation of coffee drinking to coronary artery disease (CAD) risk remains unresolved. Using Cox proportional-hazards models with 5 covariates, 127,212 subjects who supplied baseline data at voluntary health examinations from 1978 to 1985 were studied. Subsequently, 8,357 subjects were hospitalized for CAD. Coffee drinking was unrelated to CAD risk in 58,888 never smokers, but in ex-smokers and current baseline smokers, daily coffee intake was associated with higher CAD risk. This disparity was generally consistent in stratified subgroups. In conclusion, this relation of coffee consumption to increased CAD risk only in smokers could be explained by incomplete control for smoking, by other traits of smokers, or by an adverse biologic interaction of a coffee ingredient with smoking effect on CAD.

Objectives This study examined the relation between alcohol use and utilization of health services during a 3-year period in a sample of 4,264 adult respondents to a member health survey in a health maintenance organization. Methods Respondents were categorized as abstainers (no drinks in the past year, n = 1,139), lighter drinkers (less than seven drinks/week, n = 2,330), moderate drinkers (seven to 13 drinks/week, n = 498), and heavier drinkers (> or =14 drinks/week, n = 297). Each drinker group was compared with abstainers on outpatient visits, hospital days, and number of hospitalizations controlling for age, race, and health plan membership. Results The mean number of outpatient visits was inversely related to the amount of alcohol consumed. Significant differences also were found for mean number of hospitalizations and mean days hospitalized per year. Compared with the three drinker groups, abstainers were significantly higher on both inpatient measures. Conclusions These results might be explained by the inclusion in the abstainer group of exdrinkers who quit because of illness, inattention to health problems by heavier drinkers, or lower rates of illness among drinkers. The findings underscore the importance of replicating our study in other cohorts in which problem drinkers can be identified and compared with non-problem drinkers and in which lifelong abstainers can be separated from exdrinkers in the analysis.

Objective To determine the relationship between the use of low-dose (less than 50 /mg estrogen) oral contraceptives (OC) and myocardial infarction. Methods In this population-based case-control study, all incident myocardial infarctions in women, ages 15–44 years who were members of the Kaiser Permanente Medical Care Program, Northern and Southern California regions were ascertained during a 39-month period from 1991 through 1994. For each woman with myocardial infarction, up to three age- and facility-matched controls were chosen at random from female members. Information about OC use (predominantly low-dose preparations) was obtained in face-to-face interviews. Results There were 187 incident cases of myocardial infarction during 3.6 million woman-years of observation (incidence rate, 5.2 per 100,000 woman-years). The prevalence of several risk factors for myocardial infarction was lower in controls who were current users of OCs than in controls who were noncurrent (past and never) users. The odds ratio for myocardial infarction in current OC users compared with noncurrent users was 1.65 (95% confidence interval 0.45, 6.06) after adjustment for major risk factors and for race and ethnicity, corresponding to an excess risk of less than one case per 100,000 woman-years. The study had 80% power to detect a relative risk of 2.3 (one-sided test, α = .05). The odds ratio of myocardial infarction in past OC users was not elevated. Conclusion With respect to myocardial infarction, low-dose oral contraceptives can be used safely by women who lack risk factors for coronary heart disease.

Objectives: To review the effect of specific types of alcoholic drink on coronary risk. Design: Systematic review of ecological, case-control, and cohort studies in which specific associations were available for consumption of beer, wine, and spirits and risk of coronary heart disease. Subjects: 12 ecological, three case-control, and 10 separate prospective cohort studies. Main outcome measures: Alcohol consumption and relative risk of morbidity and mortality from coronary heart disease. Results: Most ecological studies suggested that wine was more effective in reducing risk of mortality from heart disease than beer or spirits. Taken together, the three case-control studies did not suggest that one type of drink was more cardioprotective than the others. Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found such an association for beer, and four for spirits. Conclusions: Results from observational studies, where alcohol consumption can be linked directly to an individual9s risk of coronary heart disease, provide strong evidence that all alcoholic drinks are linked with lower risk. Thus, a substantial portion of the benefit is from alcohol rather than other components of each type of drink. Key messages Key messages We examined the relation between specific alcoholic drinks and reduction of risk of coronary heart disease by summarising published reports from ecological, case-control, and cohort studies Most ecological studies suggested that wine was more effective in reducing risk of mortality than beer or spirits, whereas the three case-control studies together did not suggest that one type of drink was more cardioprotective than others Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found the association for beer, and four found it for spirits. The evidence suggests that all alcoholic drinks are linked with lower risk, so that much of the benefit is from alcohol rather than other components of each type of drink

▪ Abstract Disparities in the relationships between alcohol consumption and various cardiovascular conditions are now evident, with complex interrelationships between conditions. An inverse relationship of alcohol use to coronary heart disease is supported by many population studies. Interpretation of these data as a protective effect of alcohol against coronary disease is strengthened by plausible mechanisms. Although some experimental data suggest the hypothesis that wine, in particular, has additional protective benefit, prospective studies show no consensus on this point. Strong, consistent epidemiologic data support a relationship of heavier drinking to hypertension. Intervention studies show a pressor effect of alcohol, which appears and regresses within several days, but a mechanism has not yet been established. As with most aspects of alcohol and health effects, the data do not suggest monotonic relationships of alcohol with these conditions. Thus, amount of alcohol taken is a crucial consideration. Advice to concerned persons needs to take into account individual factors in drinkers or potential drinkers.

To supplement sparse data about ischemic heart disease in Asian Americans, hospitalization risk was prospectively examined in a group of Asian Americans living in Northern California. Analyses used Cox models with ischemic heart disease risk traits as covariables. With Whites as the referent category, relative risks by ethnic group were as follows: Chinese, 0.6 (P = .001); Japanese, 1.0 (P = .97); Filipinos, 1.0 (P = .95); South Asians, 3.7 (P < .001); other Asian Americans, 0.8 (P = .55). Thus, unexplained differences in ischemic heart disease risk exist among Asian-American ethnic groups, with Chinese Americans at lowest risk and persons of South Asian origin at highest risk.

The heart failure syndrome (HF) has diverse etiologies. In a 22-year study of predictors of HF in 126,235 persons, we attempted to identify etiologic factors independent of associated coronary heart disease (CAD) in 2594 persons hospitalized for the condition. For this purpose, subjects were stratified according to whether CAD was present. Of the subjects, 60% had evidence for CAD (CAD-HF). Because we also wished to study HF predictors in subjects without associated CAD according to specific HF etiology, the paper records of the other 40% of subjects (non-CAD-HF) underwent a detailed review so that we could determine the apparent primary etiology and contributory factors. A random sample of all subjects with CAD-HF underwent a similar paper record review so that we could ascertain contributory factors. The primary etiology among the subjects with non-CAD-HF was categorized as systemic hypertension (HTN) in 354, valve disease in 110, cardiomyopathies (including alcoholic and idiopathic) in 93, other specific miscellaneous in 55, and primary etiology not evident (unclear) in 423. The unclear-group subjects generally had multiple probable contributing factors. In addition to the preponderant etiology in subjects with non-CAD-HF, the mean number of contributory factors was 1.5; among subjects with CAD-HF, the mean number of contributory factors was 1.9. Frequent additional factors, in both CAD-HF and non-CAD-HF, were HTN, diabetes mellitus, atrial fibrillation, and heavy alcohol consumption. These data show that primary HF etiology is often uncertain and that HF etiology is usually multifactorial, whether or not CAD is present.

Purpose: We studied the hypothesis that possibly via shared inflammatory mechanisms, psoriatic arthritis (PsA) is associated with increased prevalence of cardiovascular (CV) conditions. Methods: Among a multiethnic population of 76,465 men and women with known demographics, we studied all persons (n = 99) with confirmed outpatient diagnoses of PsA. Associations of PsA with CV diagnoses were studied in the entire population by logistic regression with six covariates. With two matched control study subjects for each study subject with PsA, selected risk traits for CV conditions at time of PsA diagnosis were compared with findings on t-tests. Results: Study subjects with PsA did not exhibit more atherothrombotic disease (coronary and cerebrovascular) or diabetes mellitus but had increased prevalence of systemic hypertension and heart failure compared with study control subjects. In the case-control analysis, study subjects with PsA had a lower mean blood cholesterol, a higher mean body mass index, and a higher mean blood pressure compared with study control subjects; mean blood glucose was similar in both groups. Conclusions: In this analysis the associations of PsA with CV risk factors and CV conditions are mixed. Except for increased systemic hypertension, it is unclear whether PsA is related to higher prevalence of CV disease.

This study prospectively explores relations of usual alcohol intake in a Northern California population of 128,934 persons to risk of subsequent unnatural death. Of 385 such deaths during the 8-year study period, 88 were due to motor vehicle accidents (MVAs), 106 to suicide, 52 to homicide, and 139 to miscellaneous other unnatural causes. Comparisons of ex-drinkers and 5 levels of current drinkers to lifelong abstainers were studied by Cox proportional hazards models with 9 covariates. In adjusted analyses, persons reporting intake of 6 or more drinks daily were at greatly increased risk of death from suicide (6 times) and homicide (7 times), and at moderately increased risk of death from MVAs (2 times). Lighter and ex-drinkers were not at significantly increased risk for all unnatural deaths or any of its subsets. Among persons reporting 6 or more drinks/day, women and persons below 50 years of age were at especially high risk, but Blacks and Whites were at similar risk. Persons who usually drank liquor or wine were at greater risk for MVAs than those who usually drank beer; beverage choice was unrelated to the other causes of death. Among other covariates, men and not married persons were at higher risk and college graduates at lower risk, for each cause of death. The only major racial difference was a lower risk of suicide for Blacks (versus Whites). These data provide considerable detail about usual alcohol use and risk of unnatural death. They point to special need for preventive efforts among younger persons and women, with particular attention to suicide and homicide. Language: en

Since most heavy drinkers do not develop alcoholic cirrhosis, other causes or predisposing factors are probable. The authors studied traits of 128,934 adults who underwent health examinations at the Oakland and San Francisco, California, facilities of the Kaiser Permanente Medical Care Program from January 1978 to December 1985 in relation to subsequent hospitalization or death from cirrhosis of the liver. In analyses adjusted for nine covariates, past and current alcohol drinking were strongly related to cirrhosis risk, but usual choice of alcoholic beverage had no independent relation. Cigarette smoking was independently related to risk of alcoholic cirrhosis, with cigarette smokers of a pack or more per day at trebled risk compared with lifelong nonsmokers. Coffee drinking, but not tea drinking, was inversely related to alcoholic cirrhosis risk, with persons who drank four or more cups per day at one-fifth the risk of noncoffee drinkers. This inverse relation between coffee consumption and risk of alcoholic cirrhosis was consistent in many subsets, including persons free of gastrointestinal disease and those with 5 or more years before hospitalization or death. Cigarette smoking and coffee consumption were not consistently related to risk of hospitalization or death for nonalcoholic cirrhosis. These data could mean that cigarette smoking promotes alcoholic cirrhosis and that coffee drinking might be protective.

We studied the relationship of race to incidence of hospitalization for cerebrovascular disease among 74,096 white and 33,041 black persons who took health examinations in a prepaid health care program. Analyses were controlled for age, sex, body mass index, coffee use, smoking, alcohol use, systolic blood pressure, and baseline disease. Blacks were at higher hospitalization risk than whites for hemorrhagic cerebrovascular disease (relative risk = 2.4, 95% confidence interval = 1.3-5.8), cerebral thrombosis (relative risk = 1.9, 95% confidence interval = 1.2-2.9), and nonspecific cerebrovascular disease (relative risk = 1.6, 95% confidence interval = 1.2-2.2) but at lower hospitalization risk for extracranial occlusive disease (relative risk = 0.4, 95% confidence interval = 0.2-0.7). Blood pressure had a similar relation to all types of cerebrovascular disease in both races, but there were disparities in the relations of other atherosclerosis risk factors to different types of cerebrovascular disease. Educational attainment had little relation to hospitalization for extracranial occlusive disease, a finding that reduces the likelihood that selection bias explains the racial disparity. These data show unexplained racial differences in the type and location of cerebrovascular disease. The differences are important in understanding the pathogenesis of cerebrovascular disease and have practical clinical implications.

In recent decades alcohol use has joined other correlates of hypertension (HTN), such as obesity and salt intake, as a major research focus about HTN risk factors. In cross-sectional and prospective epidemiologic studies, higher blood pressure (BP) has consistently been found among persons reporting usual daily intake of three standard-sized drinks or more. Although definitive mechanisms have not been established, several aspects of the data, including short and intermediate term experiments, suggest a causal relationship. Heavier drinking may, in fact, be the commonest cause of reversible HTN, and reduction of heavy alcohol intake plays an important public health role in HTN management. Additional to the mechanism, unresolved issues about the alcohol-BP relationship include whether there is a threshold dosage of alcohol for association with HTN, the sequelae of alcohol-associated HTN and the roles of interactions with gender, ethnicity, other lifestyle traits, drinking pattern, and choice of beverage. This article reviews these areas and includes new data about the beverage choice aspect.

reduces the risk ofAlzheimer’s disease.” With the hintof greater longevity what non-redwine drinker wouldn’t feel pressureto start a red wine habit? What per-son over age 65 years wouldn’t con-sider a lifestyle change that prom-ised a lower chance of Alzheimer’s?The public has heard the impliedmessage. A

Disparities in associations of alcohol consumption to various cardiovascular conditions lead to separate consideration of several. These include (1) Alcoholic cardiomyopathy from chronic heavy drinking in susceptible persons. (2) Higher blood pressure (hypertension) in some heavier drinkers. (3) A relation of drinking to higher risk of hemorrhagic stroke but to lower risk of ischemic stroke. (4) Certain arrhythmias, especially among binge drinkers. (5) An inverse relation of alcohol use to coronary artery disease. A causal hypothesis of protection is strengthened by plausible mechanisms. The coronary disease data impact upon total mortality statistics, such that lighter drinkers are at slightly lower risk than abstainers of death within a given time period. (6) An inverse relation of drinking to type 2 (adult onset) diabetes mellitus in several recent studies. Because of close relations to cardiovascular disorders, diabetes is considered virtual cardiovascular "equivalent". (7) Composites of (1-6) result in a complex association between alcohol and the common heart failure syndrome. International comparisons suggest wine is more protective against coronary disease than liquor or beer. Reports of antioxidants, endothelial relaxants, and antithrombotic activity in wine (especially red) support hypothetical benefit from non-alcohol wine components. However, prospective population studies show apparent protection from beer, wine, or liquor. Thus, some suggest that favorable traits or drinking patterns of wine drinkers might explain the international comparison findings. Amount of alcohol taken is a crucial consideration in alcohol-health relations. Advice to concerned persons needs to take into account individual risk/benefit factors in drinkers or potential drinkers.

Background: A minority of persons at risk develop liver cirrhosis, but knowledge of risk modulators is sparse. Several reports suggest that coffee drinking is associated with lower cirrhosis risk. Methods: We studied 125 580 multiethnic members of a comprehensive prepaid health care plan without known liver disease who supplied baseline data at voluntary health examinations from 1978 to 1985. Subsequently, through 2001, 330 of them were diagnosed with liver cirrhosis. Review of medical records confirmed the diagnosis of cirrhosis and ascertained probable etiology. The association of coffee drinking with cirrhosis was estimated by Cox proportional hazards models with 7 covariates. We also did a cross-sectional analysis of baseline aspartate aminotransferase and alanine aminotransferase levels, studied by logistic regression. Results: In the cohort study, relative risks of alcoholic cirrhosis (199 subjects) for coffee drinking (vs none) were less than 1 cup per day, 0.7 (95% confidence interval [CI], 0.4-1.1); 1 to 3 cups, 0.6 (95% CI, 0.4-0.8;P.001); and 4 or more cups, 0.2 (95% CI, 0.1-0.4; P.001). For 131 subjects with nonalcoholic cirrhosis, relative risks were less than 1 cup, 1.2 (95% CI, 0.6-2.2); 1 to 3 cups, 1.3 (95% CI, 0.8-2.1); and 4 or more cups, 0.7 (95% CI, 0.41.3). These relative risks for coffee drinking were consistent in subsets. Tea drinking was unrelated to alcoholic or nonalcoholic cirrhosis. In the cross-sectional analyses, coffee drinking was related to lower prevalence of high aspartate aminotransferase and alanine aminotransferase levels; for example, the odds ratio of 4 or more cups per day (vs none) for a high aspartate aminotransferase level was 0.5 (95% CI, 0.4-0.6;P.001) and for a high alanine aminotransferase level, 0.6 (95% CI, 0.6-0.7;P.001), with stronger inverse relations in those who drink large quantities of alcohol. Conclusion: These data support the hypothesis that there is an ingredient in coffee that protects against cirrhosis, especially alcoholic cirrhosis. Arch Intern Med. 2006;166:1190-1195

To the Editor: Defined as persons of Indian, Pakistani, Bangladeshi, or Sri Lankan ancestry, the South Asian (SA) population is believed to have a higher risk of coronary artery disease (CAD) than that of other ethnic groups [(1–6)][1]. Substantial evidence comes mostly from prevalence data or

To determine the risk for malignant primary adult-onset glioma (MPAG) associated with cigarette smoking and other lifestyle behaviors in a large, multiethnic, managed-care cohort.The study population included a cohort of 133,811 subscribers to the Kaiser Permanente Medical Care Program of Northern California who had received a multiphasic health checkup and questionnaire between 1977 and 1985, were at least 25 years old at their start of follow-up, and had no prior history of benign or malignant brain tumors. In this cohort, patients were followed for up to 21 years for the development of MPAG.Risk for MPAG among women increased with increasing packs of cigarettes smoked per day (p-for-trend = 0.04), adjusting for cigar and pipe smoking, patient age, sex, race, education, alcohol use and coffee consumption. A similar pattern was not observed for men. Individuals who smoked marijuana at least once a month, adjusting for cigarette smoking (packs smoked per day) and for the factors noted above, had a 2.8-fold (CI = 1.3-6.2) increased risk for MPAG. Relative risk for MPAG increased with increasing consumption of coffee (p-for-trend = 0.05).Cigarette smoking was associated with an increased risk for MPAG among women but not among men. Individuals who smoked marijuana at least once a month had an increased risk for MPAG, although no dose-response relation was observed. Drinkers of7 cups of coffee per day had a 70% increased risk for MPAG and smaller risk elevation for lower consumption. Alcohol usage was not associated with an increased risk for MPAG.

OBJECTIVES: We studied relationships of cigarette smoking and coffee drinking to risk of pancreatitis. METHODS: This was a cohort study among 129,000 prepaid health plan members who supplied data about demographics and habits in 1978-85. Among 439 persons subsequently hospitalized for pancreatitis, probable etiologic associations were cholelithiasis (168/439 = 38%), alcohol (125/439 = 29%), idiopathic (110/430 = 25%), and miscellaneous (36/439 = 8%). Cox proportional hazards models with seven covariates (including alcohol intake) yielded relative risk estimates for smoking and coffee use. RESULTS: Increasing smoking was strongly related to increased risk of alcohol-associated pancreatitis, less related to idiopathic pancreatitis, and unrelated to gallstone-associated pancreatitis. Relative risks (95% confidence intervals, Cl) of one pack per day (vs never) smokers for pancreatitis groups were: alcohol = 4.9 (2.2-11.2, p < 0.001), idiopathic = 3.1 (1.4-7.2, p < 0.01), and gallstone = 1.3 (0.6-3.1). The relationship of smoking to alcohol-associated pancreatitis was consistent in sex and race subsets. Drinking coffee, but not tea, was weakly inversely related to risk only of alcohol-associated pancreatitis, with relative risk (95% Cl) per cup per day = 0.85 (0.77-0.95; p = 0.003). Male sex, black ethnicity, and lower-educational attainment were other predictors of alcohol-associated pancreatitis. CONCLUSIONS: Cigarette smoking is an Independent risk factor for alcohol-associated and idiopathic pancreatitis. Coffee drinking is associated with reduced risk of alcohol-associated pancreatitis. The data are compatible with the hypotheses that smoking may be toxic to the pancreas or may potentiate other pancreatic toxins while some ingredient in coffee may have a modulating effect.