Prehypertension and its Risk Factors in Suburban Nepal -Findings from the Dhulikhel Heart Study.

Background Prehypertension, defined as a systolic blood pressure of 120-139 mmHg or a diastolic blood pressure of 80-89 mmHg, leads to higher rates of incident hypertension, and is associated with excess morbidity and deaths from cardiovascular diseases. Objective To estimate the prevalence of and examine the factors associated with prehypertension in Dhulikhel. Method This cross-sectional study utilized data from the 752 participants of the Dhulikhel Heart Study (DHS). The data collectors interviewed the participants at their home using a tablet based structured pre-tested questionnaire and measured blood pressure using a standard digital blood pressure machine (Microlife, Switzerland). Multivariate analysis was conducted using generalized estimating equations with multivariate logistic regression (with household as cluster) adjusting for age, sex, ethnicity, marital status, income, education, alcohol consumption, smoking, physical activity, body mass index (BMI) and food consumption. Result Males had a three-fold higher odds of prehypertension than females (OR:3.17, 95% CI:1.91-5.26). The odds of prehypertension increased with being overweight (OR:2.29, 95% CI:1.42-3.70) and with being obese (OR:5.00, 95% CI:1.81-13.79) compared to normal BMI. Education reduced the odds of developing prehypertension (OR:0.51, 95% CI:0.29-0.91). Those who met the recommended level of physical activity (OR:0.61, 95% CI:0.40-0.95) also were associated with lower prehypertension prevalence. Conclusion Obese/overweight and being male increased the odds of prehypertension whereas formal education and recommended level of physical activities were associated with lower prehypertension prevalence. Primordial prevention against cardiovascular risk factors at the community level, especially targeting the young adult male, is imperative.

Quit Intentions and Attempts among Smokers in Sub-urban Nepal: Findings from the Dhulikhel Heart Study.

Background The most effective way for smokers to avoid or minimize the harmful effects is to quit smoking. Smoking cessation has been attributed to multiple factors operating at physiological, psychological, environmental and social level. There is common consensus that smoking cessation programs should be tailored for specific populations. However, there has been lack of data regarding factors that influence smoking cessation in Nepal, which has hindered the development of effective smoking-cessation interventions. Objective To assess the prevalence of quit attempts, successful quitting and the factors associated with them in a randomly selected, population-based adult participants in sub-urban Nepal. Method This cross-sectional study utilized data from the first wave of the baseline survey of the Dhulikhel Heart Study (DHS). A total of 2225 households of Dhulikhel city were enumerated and a third of the households (n=735) were randomly selected. Questions on tobacco use were ascertained using the questions based on the WHO STEPS survey questionnaire and questions on past quit attempts. Result Out of 1073 participants, 248 (23.1%) were current smokers and 99 (9.2%) were former smokers. Only 58% of the current smokers mentioned that they had attempted to quit smoking. When asked if they were interested in quitting if helped, almost 90.5% mentioned they were willing. Brahmins were less likely to have quit smoking (former smoker) compared to Newars (OR: 0.41, 95% CI: 0.18-0.90). We also observed that those who had high alcohol consumption were less likely to have quit smoking (OR: 0.36, 95% CI: 0.17-0.76). We didn't find any meaningful significant association between socio-demographic factors or other CVD risk factors and the quit attempts. Conclusion As the country braces to address the burden of non-communicable diseases in Nepal, it is crucial to incorporate tobacco cessation programs in the national health system to meet the global target of bringing tobacco consumption to less than 5% by 2040. We recommend future studies to get a broader understanding of quit effort and factors associated with thereby supporting the development of evidence-based strategies to address tobacco cessation.

Prevalence and Correlates of Tobacco Use in a Suburban community of Nepal: Findings from the Dhulikhel Heart Study.

Background Smoking and oral tobacco use are important risk factors for cancer and other chronic diseases. The distribution of tobacco consumption in Nepal varies across the population subgroups. There is little information on the correlates of tobacco use among suburban population in Nepal. Objective To estimate the prevalence of smoking and oral tobacco use; and determine the socio-demographic and other CVD risk factors associated with them in a suburban population of Dhulikhel, Nepal. Method This cross sectional study utilized data from the first wave of the baseline survey of the Dhulikhel Heart Study (DHS). A total of 2225 households of Dhulikhel city were enumerated and a third of the households (n=735) were randomly selected. Questions on tobacco use were ascertained from 1073 adults age 18 years and older using the questions based on the WHO STEPS survey questionnaire. Result More than a third (36%) of the men were current smokers and 12% reported regular use of oral tobacco. About 14% of the women were current smokers and only 0.5% reported to use oral tobacco regularly.In the multivariate analysis, sex, ethnicity, education, alcohol consumption and body mass index were significantly associated with tobacco use. Males were 2.6 times as likely as females to smoke (95%: 1.53-4.59; p<0.001). Brahmin/Chhetri were 2.8 times more likely to smoke compared to Newars (95% Ci: 1.53-5.18; p=0.001). Education reduced the odds of smoking; compared to those with no formal education, those with up to high school and those with a high school degree or higher were 0.50 (95% CI: 0.27-0.92; p=0.02 ) and 0.38 (95% CI: 0.16-0.91; p=0.03) percent less likely to smoke, respectively. Moderate drinkers were 8 times more likely (95% CI: .54 - 18.40; p<0.001) and high drinkers were 13 times (95% CI: 6.63 - 24.26; p<0.001) compared to non-drinkers. Regarding oral tobacco use males were 15 times as likely as females to use oral tobacco (95% CI: 4.1-58.8; p<0.001). Compared to Newars, Brahmin/Chhetri were 2.7 times as likely to use oral tobacco (95% CI: 1.08 - 6.66; p=0.03). Conclusion Although Nepal has made some progress in passing progressive laws for tobacco control, and national surveys have shown slight reduction on tobacco use, this is far from satisfactory to meet the global target of bringing tobacco consumption to less than 5% by 2040. We recommend future studies to focus on socio-cultural, gender and behavioral aspects of tobacco use in addition to the epidemiological aspects.

Topographical Differences of Infant Mortality in Nepal.

Background Infant mortality is a major problem in Nepal, particularly in the mountainous region of the country. Objective To identify factors that contributes to the high rate of infant mortality in the mountain zone in Nepal. Method Data were derived from the 2011 Nepal Demographic and Health Survey (NDHS). Infant mortality was analyzed across three ecological zones in a sample of 5,306 live births in the five years preceding the survey. The contribution of risk factors to the excess infant mortality was assessed using multiple logistic regression. Result Infant mortality rate (deaths per 1000 live births) in the ecological zones were 59 (95% CI: 36, 81), 44 (35, 53), and 40 (33, 47) for the mountain, hill and terai zones, respectively. Women living in the mountain zone were more likely to report that distance to care was a "big problem" and had a greater risk of infant mortality compared to the terai zone (OR=1.42, 95% CI: 1.01, 2.02, p=0.04). This increased risk was observed only among births to mothers who perceived distance to the nearest health facility as a "big problem" (aOR=1.57, 95% CI: 1.01, 2.40, p=0.04) controlling for other risk factors. Conclusion These findings suggest that the higher Infant mortality rate (IMR) in the mountain zone was among the women who perceived distance to health facilities as a big problem. Improved accessibility to health services, particularly in this zone, is an essential strategy for reducing infant mortality in Nepal.

Estimation of Causes of Death in Suburban Nepal Using Verbal Autopsy.

Background Nepal is in the midst of a disease transition, including a rapid increase of noncommunicable diseases. In order for health policy makers and planners to make informed programmatic and funding decisions, they need up to date and accurate data regarding cause of death throughout the country. Methods of improving cause of death reporting in Nepal are urgently required. Objective We sought to validate SmartVA-Analyze, an application which computer certifies verbal autopsies, to evaluate it as a method for collecting mortality data in Nepal. Method We conducted a medical record review of mortality cases at Dhulikhel Hospital, Kathmandu University Hospital. Cases with a verifiable underlying cause of death were used as gold standard reference cases. Verbal autopsies were conducted with caregivers of 48 gold standard cases. Result Of the 66 adult gold standard mortality cases reviewed, 76% were caused by cancer, cirrhosis, cardiovascular disease, COPD or injury. When assessing concordance between cause of death from verbal autopsy vs. gold standards, we found an overall agreement (Kappa) of 0.50. Kappa based on broader ICD-10 categories was 0.69. Cause-Specific Mortality Fraction Accuracy was 0.625, and disease specific measures of concordance varied widely, with sensitivities ranging from 0-100%. Conclusion Ongoing, countrywide mortality data collection is crucial for evidence-based priority setting in Nepal. Though not valid for all causes, we found SmartVA-Analyze to provide useful general cause of death data, particularly in settings where death certification is unavailable.

A novel Alzheimer disease locus located near the gene encoding tau protein.

APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10(-6)) and temporal cortex (P=2.6 × 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.

Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.

A genome-wide association meta-analysis of plasma Aß peptides concentrations in the elderly.

Amyloid beta (Aß) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aß peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aß peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aß-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aß1-40 and Aß1-42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10(-)(5)). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aß1-42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aß1-42 secretion. In conclusion, our study results suggest that plasma Aß peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.

Risk Factors for Pneumonia in Children under 5 Years in a Teaching Hospital in Nepal.

BACKGROUND: Pneumonia is a leading cause of mortality among children under-five years of age globally. The WHO (2014) has reported that indoor air pollution caused by cooking and heating with biomass fuel, living in crowed homes and parenting smoking are risk factors of pneumonia. OBJECTIVES: The objective of the study was to identify the risk factors for pneumonia among children under-5 years of age. METHODS: A case control study was carried out among the mothers having under-5 years children who were admitted in the paediatric ward of Dhulikhel Hospital in 2012/13. A convenience sampling technique was used to select 50 children with pneumonia and 150 children with non-pneumonia diseases matched on age, sex and setting. A semi-structured interview consisting of questions related to risk factors for pneumonia was used to collect data from mothers of both cases and controls. RESULTS: Sex of the child did not differ by case/control group whereas the children with pneumonia were slightly older with 26% cases and 15% controls older than 3 years of age. Mother's education was similar in both groups as was family income. Living in a household with a chulo with smoke increased the odds of having pneumonia significantly, with the risk almost 4 times greater if the chulo was located within the same building (OR: 3.76, 95% CI: 1.20-11.82, p=0.02). Children who had diarrhea in the past 3 months were protected from pneumonia (OR: 0.38, 95% CI: 0.18- 0.82, p=0.01). An increasing trend of pneumonia was observed among children of tobacco smoking parents with greater risk if both parents smoked; it was, however, not statically significant (OR: 2.21, 95% CI: 0.56-8.82, p=0.26). CONCLUSION: The present study suggests that two factors related to smoke, presence of a smoky chulo in a household and both parents smoking, are modifiable risk factors related to pneumonia in young children. Reliable longitudinal studies, interventions, and programs to educate parents in prevention are important for reducing mortality and morbidities related to acute respiratory illnesses in Nepal.

ATP5H/KCTD2 locus is associated with Alzheimer's disease risk.

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10(-6) were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10(-7) in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.

Cancer linked to Alzheimer disease but not vascular dementia.

OBJECTIVE: To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD). METHODS: Cox proportional hazards models were used to test associations between prevalent dementia and risk of future cancer hospitalization, and associations between prevalent cancer and risk of subsequent dementia. Participants in the Cardiovascular Health Study-Cognition Substudy, a prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean of 5.4 years for dementia and 8.3 years for cancer. RESULTS: The presence of any AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.20-0.84) and pure AD (HR = 0.31, 95% CI = 0.12-0.86) was associated with a reduced risk of future cancer hospitalization, adjusted for demographic factors, smoking, obesity, and physical activity. No significant associations were found between dementia at baseline and rate of cancer hospitalizations for participants with diagnoses of VaD. Prevalent cancer was associated with reduced risk of any AD (HR = 0.72; 95% CI = 0.52-0.997) and pure AD (HR = 0.57; 95% CI = 0.36-0.90) among white subjects after adjustment for demographics, number of APOE epsilon4 alleles, hypertension, diabetes, and coronary heart disease; the opposite association was found among minorities, but the sample size was too small to provide stable estimates. No significant association was found between cancer and subsequent development of VaD. CONCLUSIONS: In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration.

Knee height and arm span: a reflection of early life environment and risk of dementia.

OBJECTIVES: To determine if anthropometric measures, as markers of early life environment, are associated with risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD). METHODS: A total of 2,798 subjects were followed as part of the Cardiovascular Health Cognition Study for an average of 5.4 years; 480 developed dementia. Knee height was measured 3 years prior to and arm span 4 years after the study's baseline. Cox proportional hazard models were used to examine their association with subsequent risk of dementia, AD, and VaD. RESULTS: Among women, greater knee height and arm span were associated with lower risks of dementia (knee height: HR per 1-inch increase 0.84; 95% CI 0.74-0.96; arm span: HR per 1-inch increase 0.93; 95% CI 0.88-0.98) and AD (knee height: HR per 1-inch increase 0.78; 95% CI 0.65-0.93; arm span: HR per 1-inch increase 0.90; 95% CI 0.85-0.96). Women in the lowest quartile of arm span had approximately 1.5 times greater risk of dementia (HR 1.45; 95% CI 1.03-2.05) and AD (HR 1.70; 95% CI 1.10-2.62) than other women. Among men, only arm span was associated with lower risks of dementia (HR per 1-inch increase 0.94; 95% CI 0.89-1.00) and AD (HR per 1-inch increase 0.92; 95% CI 0.84-1.00). For each gender, knee height was not associated with VaD, while arm span was associated with a nonsignificant lower risk of VaD. CONCLUSIONS: Our findings with knee height and arm span are consistent with previous reports and suggest early life environment may play an important role in the determination of future dementia risk.

NSAID use and dementia risk in the Cardiovascular Health Study: role of APOE and NSAID type.

BACKGROUND: Epidemiologic and laboratory studies suggest that nonsteroidal antiinflammatory drugs (NSAIDs) reduce risk of Alzheimer disease (AD). We therefore investigated the association between use of NSAIDs, aspirin, and the non-NSAID analgesic acetaminophen with incidence of dementia and AD. METHODS: Participants in the Cardiovascular Health Cognition Study included 3,229 individuals aged 65 or older, free of dementia at baseline, with information on medication use. We used Cox proportional hazards regression to estimate the association of medication use with incident all-cause dementia, AD, and vascular dementia (VaD). Additional analyses considered the NSAID-AD relationship as a function of age, presence of at least one epsilon 4 allele at APOE, race, and individual NSAIDs' reported ability to reduce production of the amyloid-beta peptide variant A beta(42). RESULTS: Use of NSAIDs was associated with a lower risk of dementia (adjusted hazard ratio or aHR 0.76, 95% CI or CI 0.60-0.96) and, in particular, AD (aHR 0.63, CI 0.45-0.88), but not VaD (aHR 0.92, CI 0.65-1.28). No similar trends were observed with acetaminophen (aHR 0.99, CI 0.79-1.24). Closer examination suggested AD risk reduction with NSAIDs only in participants having an APOE epsilon 4 allele (aHR 0.34, CI 0.18-0.65; aHR for others 0.88, CI 0.59-1.32). There was no advantage in AD risk reduction with NSAIDs reported to selectively reduce A beta(42). CONCLUSIONS: Results were consistent with previous cohort studies showing reduced risk of AD in NSAID users, but this association was found only in those with an APOE epsilon 4 allele, and there was no advantage for A beta(42)-lowering NSAIDs.

Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.

OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS). METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician's assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4. RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28% (95% CI: 0.51 to 1.02), and AD by 41% (95% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect. CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.

Hypertension, heart rate, use of antihypertensives, and incident prostate cancer.

PURPOSE: Recent studies have reported conflicting results on a possible relationship between hypertension, heart rate, and prostate cancer. A model has been developed suggesting that high blood pressure and high heart rate may both be markers for increased central sympathetic nervous activity, which may result in androgen-mediated stimulation of prostate cancer growth. METHODS: In this study we examined the associations between hypertension, heart rate, use of antihypertensive medications, and incident prostate cancer in a cohort of 2442 men. Data from the Cardiovascular Health Study (CHS), an NHLBI-sponsored observational study of adults age 65 or older in four U.S. communities, were analyzed using Cox proportional hazards regression. Seated systolic and diastolic blood pressures were measured using a standardized protocol at the initial clinical examination and annually at follow-up visits. Medications data were transcribed by trained interviewers from prescription medication containers brought into the clinic by participants. RESULTS: A total of 209 cases of incident prostate cancer were identified from either an ICD-9 code of 185 in hospital medical records (n = 130) or by self-report from annual surveillance interviews (n = 79). An average of 5.6 years of follow-up was available for analyses. No associations between blood pressure measures at entry into the study and prostate cancer were found, although these results may have been affected by subsequent treatment of hypertension. An association between resting heart rate (HR) equal to or greater than 80 beats per minute and incident prostate cancer was found compared to men with a rate of less than 60 beats per minute (HR: 1.6, 95% confidence interval [CI]: 1.03-2.5). An inverse association was found between risk of incident prostate cancer and use of any antihypertensive medication (HR: 0.7, 95% CI: 0.5-0.9). A test of heterogeneity found no difference between use of the specific classes of antihypertensive medication and the association with prostate cancer risk. CONCLUSIONS: These data tend to support the hypothesized causal pathway between vascular disease markers and prostate cancer.

Use of calcium channel blockers and breast carcinoma risk in postmenopausal women.

BACKGROUND: The use of calcium channel blockers in an elderly population recently was reported to be associated with the incidence of cancer. The Cardiovascular Health Study, a multisite observational cohort study, provided the opportunity to investigate the epidemiologic association between the use of calcium channel blockers and breast carcinoma risk in 3198 women age > or = 65 years. METHODS: Standard questionnaires and clinical procedures were administered at four study sites annually from 1989-1990 to 1993-1994. Drug usage was assessed by a medication inventory and hospitalizations for 75 incident invasive breast carcinoma cases were identified using International Classification of Diseases-9 Clinical Modification codes. Time-dependent Cox proportional hazards regression models were used to assess associations between incident breast carcinoma and the use of specific antihypertensive medication including calcium channel blockers. RESULTS: In adjusted Cox proportional hazards models, an elevated risk of breast carcinoma was associated with use of calcium channel blockers (hazard ratio [HR]: 2.57; 95% confidence interval [CI], 1.47-4.49). This association persisted when the comparison group was users of other antihypertensive medication. No associations between the use of other antihypertensive medication with incident breast carcinoma were found. Associations were enhanced by assessment of high dose at baseline (HR: 4.42; 95% CI, 1.37-14.27) and when calcium channel blockers were combined with estrogen use (HR: 4.48; 95% CI, 1.58-12.75). The association was found to be strongest for the use of estrogens with immediate release calcium channel blockers (HR: 8.48; 95% CI, 2.99-24.08). CONCLUSIONS: Although the number of cases was limited in this observational study, associations found between the use of calcium channel blockers and incident invasive breast carcinoma warrant further investigation. Site specific carcinomas should be included as an outcome of ongoing and planned long term clinical trials using calcium channel blockers.

Surveillance and ascertainment of cardiovascular events. The Cardiovascular Health Study.

While previous prospective multicenter studies have conducted cardiovascular disease surveillance, few have detailed the techniques relating to the ascertainment of and data collection for events. The Cardiovascular Health Study (CHS) is a population-based study of coronary heart disease and stroke in older adults. This article summarizes the CHS events protocol and describes the methods of surveillance and ascertainment of hospitalized and nonhospitalized events, the use of medical records and other support documents, organizational issues at the field center level, and the classification of events through an adjudication process. We present data on incidence and mortality, the classification of adjudicated events, and the agreement between classification by the Events Subcommittee and the medical records diagnostic codes. The CHS techniques are a successful model for complete ascertainment, investigation, and documentation of events in an older cohort.