The cost-effectiveness of a uniform versus age-based threshold for one-off screening for prevention of cardiovascular disease.

The objective of this article was to assess the cost-effectiveness of screening strategies for cardiovascular diseases (CVD). A decision analytic model was constructed to estimate the costs and benefits of one-off screening strategies differentiated by screening age, sex and the threshold for initiating statin therapy ("uniform" or "age-adjusted") from the Spanish NHS perspective. The age-adjusted thresholds were configured so that the same number of people at high risk would be treated as under the uniform threshold. Health benefit was measured in quality-adjusted life years (QALY). Transition rates were estimated from the European Prospective Investigation into Cancer and Nutrition (EPIC-CVD), a large multicentre nested case-cohort study with 12 years of follow-up. Unit costs of primary care, hospitalizations and CVD care were taken from the Spanish health system. Univariate and probabilistic sensitivity analyses were employed. The comparator was no systematic screening program. The base case model showed that the most efficient one-off strategy is to screen both men and women at 40 years old using a uniform risk threshold for initiating statin treatment (Incremental Cost-Effectiveness Ratio of €3,274/QALY and €6,085/QALY for men and women, respectively). Re-allocating statin treatment towards younger individuals at high risk for their age and sex would not offset the benefit obtained using those same resources to treat older individuals. Results are sensitive to assumptions about CVD incidence rates. To conclude, one-off screening for CVD using a uniform risk threshold appears cost-effective compared with no systematic screening. These results should be evaluated in clinical studies.

Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis.

Aims: The hypothesis of 'metabolically healthy obesity' implies that, in the absence of metabolic dysfunction, individuals with excess adiposity are not at greater cardiovascular risk. We tested this hypothesis in a large pan-European prospective study. Methods and results: We conducted a case-cohort analysis in the 520 000-person European Prospective Investigation into Cancer and Nutrition study ('EPIC-CVD'). During a median follow-up of 12.2 years, we recorded 7637 incident coronary heart disease (CHD) cases. Using cut-offs recommended by guidelines, we defined obesity and overweight using body mass index (BMI), and metabolic dysfunction ('unhealthy') as ≥ 3 of elevated blood pressure, hypertriglyceridaemia, low HDL-cholesterol, hyperglycaemia, and elevated waist circumference. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CI) within each country using Prentice-weighted Cox proportional hazard regressions, accounting for age, sex, centre, education, smoking, diet, and physical activity. Compared with metabolically healthy normal weight people (reference), HRs were 2.15 (95% CI: 1.79; 2.57) for unhealthy normal weight, 2.33 (1.97; 2.76) for unhealthy overweight, and 2.54 (2.21; 2.92) for unhealthy obese people. Compared with the reference group, HRs were 1.26 (1.14; 1.40) and 1.28 (1.03; 1.58) for metabolically healthy overweight and obese people, respectively. These results were robust to various sensitivity analyses. Conclusion: Irrespective of BMI, metabolically unhealthy individuals had higher CHD risk than their healthy counterparts. Conversely, irrespective of metabolic health, overweight and obese people had higher CHD risk than lean people. These findings challenge the concept of 'metabolically healthy obesity', encouraging population-wide strategies to tackle obesity.

Relationship between drugs affecting the renin-angiotensin system and colorectal cancer: The MCC-Spain study.

The potential protective effect of renin-angiotensin system (RAS) inhibitors is a subject of increasing interest due to their possible role as chemopreventive agents against colorectal cancer (CRC). To evaluate this association, we conducted a case-control study with 2165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3912 population controls frequency matched (by age, sex and region) from the Spanish multicenter case-control study MCC-Spain. We found a significant protective effect of the angiotensin-converting enzyme Inhibitors (ACEIs) against CRC, limited to the under-65years group (OR=0.65 95%CI (0.48-0.89)) and to a lesser degree to men (OR=0.81 95%CI (0.66-0.99). In contrast, the angiotensin receptor blockers (ARBs) did not show a significant effect. Regarding the duration of use, a greater protection was observed in men as the length of consumption increases. In contrast, in the under-65 stratum, the strongest association was found in short-term treatments. Finally, by analyzing ACEIs effect by colon subsite, we found no differences, except for under 65years old, where the maximum protection was seen in the proximal intestine, descending in the distal and rectum (without statistical significance). In conclusion, our study shows a protective effect on CRC of the ACEis limited to males and people under 65years old, which increases in proximal colon in the latter. If confirmed, these results may suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location.

Association of diabetes and diabetes treatment with incidence of breast cancer.

AIMS: The aim of this study was to evaluate the association of diabetes and diabetes treatment with risk of postmenopausal breast cancer. METHODS: Histologically confirmed incident cases of postmenopausal breast (N = 916) cancer were recruited from 23 Spanish public hospitals. Population-based controls (N = 1094) were randomly selected from primary care center lists within the catchment areas of the participant hospitals. ORs (95 % CI) were estimated using mixed-effects logistic regression models, using the recruitment center as a random effect term. Breast tumors were classified into hormone receptor positive (ER+ or PR+), HER2+ and triple negative (TN). RESULTS: Diabetes was not associated with the overall risk of breast cancer (OR 1.09; 95 % CI 0.82-1.45), and it was only linked to the risk of developing TN tumors: Among 91 women with TN tumors, 18.7 % were diabetic, while the corresponding figure among controls was 9.9 % (OR 2.25; 95 % CI 1.22-4.15). Regarding treatment, results showed that insulin use was more prevalent among diabetic cases (2.5 %) as compared to diabetic controls (0.7 %); OR 2.98; 95 % CI 1.26-7.01. They also showed that, among diabetics, the risk of developing HR+/HER2- tumors decreased with longer metformin use (ORper year 0.89; 95 % CI 0.81-0.99; based on 24 cases and 43 controls). CONCLUSION: This study reinforces the need to correctly classify breast cancers when studying their association with diabetes. Given the low survival rates in women diagnosed with TN breast tumors and the potential impact of diabetes control on breast cancer prevention, more studies are needed to better characterize this association.

Validity of self-reported prevalent cases of stroke and acute myocardial infarction in the Spanish cohort of the EPIC study.

BACKGROUND: Information on the validity of self-reported cases of stroke and acute myocardial infarction (AMI) is varied. The aim of this study was to assess the validity and agreement of self-reported prevalent cases of stroke and AMI in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: At recruitment, 1992-1996, and in the follow-up (3 years after recruitment), each participant in the Spanish EPIC cohort (15,630 men and 25,808 women) was asked if a doctor had ever said that they had had a stroke or AMI, and the results were compared with information available in medical records. Validity of self-reported prevalent cases of stroke and AMI was examined by calculating sensitivity, specificity, positive predictive values and κ statistics. RESULTS: The sensitivity of self-reported prevalent cases of stroke was 81.3% and that for AMI was 97.7%. The positive predictive value was 22.2% and 60.7% for stroke and AMI, respectively, whereas specificity was very high (>99%) for both diseases. The agreement between self-report questionnaire results and medical records was substantial (κ=0.75) for AMI but not for stroke (κ=0.35). CONCLUSION: Self-reported information on stroke and AMI included in the EPIC questionnaire is a valid instrument for the assessment of AMI disease but should be used with caution in stroke.

Unfavourable life-course social gradient of coronary heart disease within Spain: a low-incidence welfare-state country.

OBJECTIVE: Social position has yet to be established as a risk factor of coronary heart disease (CHD). Our aim was to investigate an individual life-course social position gradient link with CHD incidence in the EPIC-Spain cohort. METHODS: 41,066 participants, mostly 30-65 years old, and free of cardiovascular disease at baseline (1992-1996) were followed up for a mean of 10.4 years. A combined score of paternal occupation in childhood and own adult education was used to assess individual life-course risk accumulation. Hazard ratios of CHD were estimated using Cox models, stratifying by centre, and age, and adjusting for cardiovascular risk factors. RESULTS: 583 participants (80 % men) developed a definite CHD event. Paternal occupational class IV was associated with CHD in all models in men. The educational gradient remained significant after adjusting for diet and physical activity (p = 0.01). All adjusted risk of incident CHD rose by 23 % (95 % CI 6-42 %) per category increase of life-course social position score in men. No significant associations were found in women. CONCLUSIONS: Individual life-course social position gradient was adversely related to incident CHD in Spanish men.

Saturated fat intake and alcohol consumption modulate the association between the APOE polymorphism and risk of future coronary heart disease: a nested case-control study in the Spanish EPIC cohort.

The association is still not clear between the common APOE polymorphism and coronary heart disease (CHD) risk, nor its modulation by diet. Thus, our aim was to study the association between the APOE genotypes and incident CHD and how dietary fat and alcohol consumption modify these effects. We performed a nested case-control study in the Spanish European Prospective Investigation into Cancer and Nutrition cohort. Healthy men and women (41,440, 30-69 years) were followed up over a 10-year period, with the incident CHD cases being identified. We analyzed 534 incident CHD cases and 1123 controls. APOE, dietary intake and plasma lipids were determined at baseline. The APOE polymorphism was significantly associated with low-density lipoprotein cholesterol (LDL-C), and gene-alcohol interactions in determining LDL-C were detected. In the whole population, the E2 allele was significantly associated with a lower CHD risk than E3/E3 subjects [odds ratio (OR), 0.58; 95% confidence interval (CI), 0.38-0.89]. The E4 allele did not reach statistical significance vs. E3/E3 (OR, 1.17; 95% CI, 0.88-1.58). However, saturated fat intake modified the effect of the APOE polymorphism in determining CHD risk. When saturated fat intake was low (<10% of energy), no statistically significant association between the APOE polymorphism and CHD risk was observed (P=.682). However, with higher intake (≥10%), the polymorphism was significant (P=.005), and the differences between E2 and E4 carriers were magnified (OR for E4 vs. E2, 3.33; 95% CI, 1.61-6.90). Alcohol consumption also modified the effect of the APOE on CHD risk. In conclusion, in this Mediterranean population, the E2 allele is associated with lower CHD risk, and this association is modulated by saturated fat and alcohol consumption.

Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort.

Phytosterol intake with natural foods, a measure of healthy dietary choices, increases plasma levels, but increased plasma phytosterols are believed to be a coronary heart disease (CHD) risk factor. To address this paradox, we evaluated baseline risk factors, phytosterol intake, and plasma noncholesterol sterol levels in participants of a case control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort who developed CHD (n = 299) and matched controls (n = 584) who remained free of CHD after a 10 year follow-up. Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake (P = 0.026). HDL-cholesterol level increased, and adiposity measures, cholesterol/HDL ratios, and levels of glucose, triglycerides, and lathosterol, a cholesterol synthesis marker, decreased across plasma sitosterol tertiles (P < 0.02; all). Compared with controls, cases had nonsignificantly lower median levels of phytosterol intake and plasma sitosterol. The multivariable-adjusted odds ratio for CHD across the lowest to highest plasma sitosterol tertile was 0.59 (95% confidence interval, 0.36-0.97). Associations were weaker for plasma campesterol. The apolipoprotein E genotype was unrelated to CHD risk or plasma phytosterols. The data suggest that plasma sitosterol levels are associated with a lower CHD risk while being markers of a lower cardiometabolic risk in the EPIC-Spain cohort, a population with a high phytosterol intake.

[Evaluation of the surveillance system for human immunodeficiency virus infections of Navarra, Spain, 1985-2003]. / Evaluación del sistema de información de Navarra sobre diagnósticos de infección por el VIH, 1985-2003.

BACKGROUND: Navarra has an information system of HIV diagnoses working since the beginning of the epidemic up to the present day. This study aims at describing and evaluating this system, focusing on its sensitivity. METHODS: The updated guidelines for evaluating public health surveillance systems from the CDC were used to describe the purpose and operation of the system and to analyse its attributes for the period 1985-2003. For the evaluation of the sensitivity the regional database of antiretrovirals distribution was used. RESULTS: The HIV surveillance system of Navarra is confidential and name-based, and includes all HIV-infection cases diagnosed each year. The information sources of the system are: (a) all the laboratories in the public health system that perform the western blot test, and (b) hospital discharge registries. The system covers the entire population of Navarre (584,734 inhabitants). It uses the HIV case definition proposed by the European Centre for the Epidemiological Monitoring of AIDS. The system is well-accepted by the community and by all the stakeholders, including those providing data. By the end of 2003 it included 2302 HIV cases, and 98.8% of all patients who had ever received antiretrovirals in Navarra. CONCLUSIONS: The HIV information system of Navarra is simple, useful, well-accepted and highly sensitive. The information about antiretroviral distribution was useful for this evaluation.

Smoking and myocardial infarction case-fatality: hospital and population approach.

BACKGROUND: Smoking is a risk factor for coronary heart disease, but it has been associated with better short-term prognosis in hospitalized patients with acute myocardial infarction. The aims of this study were to determine the association between smoking and myocardial infarction 28-day case-fatality in hospitalized patients and at the population level; and, whether smokers presenting with fatal myocardial infarction are more likely to die before reaching a hospital. DESIGN AND METHODS: Population-based myocardial infarction registry, carried out in 1997-1998 in seven regions of Spain, used standardized methods to find and analyze suspected myocardial infarction patients (10 654 patients; 7796 hospitalized). Four categories of smoking status were defined: never-smokers, former smokers for more than 1 year, former smokers for less than 1 year, and current smokers. RESULTS: The main end-point was 28-day case-fatality, found to be 20.1, 17.1, 15.6, and 8.9%, in the four smoking status categories, respectively, for hospitalized patients; and 37.4, 33.0, 24.5, and 23.2%, respectively, at population level. Hospitalized current smokers had lower age, sex, and comorbidity-adjusted 28-day case-fatality than never-smokers (odds ratio=0.71; 95% confidence interval: 0.56-0.90). This association held at population level (odds ratio=0.68; 95% confidence interval: 0.60-0.76), in which former smoking was also associated with lower case-fatality. In fatal cases, recent former smokers presented a lower risk of out-of-hospital death than never-smokers (odds ratio=0.47; 95% confidence interval: 0.29-0.77), whereas current smoking was marginally associated with out-of-hospital death (odds ratio=1.22; 95% confidence interval: 0.99-1.50). CONCLUSIONS: Current smoking is associated with lower 28-day case-fatality in hospitalized myocardial infarction patients. This association held at population level. Among fatal cases, smoking is associated with higher and recent former smoking with lower risk of dying out-of-hospital.

Regional variability in population acute myocardial infarction cumulative incidence and mortality rates in Spain 1997 and 1998.

BACKGROUND: Myocardial infarction (MI) incidence and mortality display a high geographic variation. AIMS: The objective of the present study was to analyze MI mortality, cumulative incidence rate variability in seven regions of Spain from 1997 to 1998. METHODS AND RESULTS: Standardized methods were used to identify, find, register, and classify MI cases that were classified as definite, possible, insufficient-data MI, and non-MI. The total population of the seven monitored regions was 7,364,682 inhabitants. Of the 11,256 cases fulfilling eligibility criteria to investigate, 10,660 were selected to calculate MI rates: 6554 (61.5%) non-fatal definite MI, 1179 (11.1%) fatal definite MI, 1859 (17.4%) fatal possible MI, 1068 (10.0%) fatal cases with insufficient data. The IBERICA 25-74 years age-standardized cumulative incidence rates for men and women, were 207 (range: 175-252) and 45 (range: 36-65) per 100,000, respectively. The age-standardized mortality rates for men and women, were 73 (range: 62-94) and 20 (range: 13-29) per 100,000, respectively. Age-standardized case-fatality was 31.4 and 24.2% in men aged 25-74 and 35-64 years, respectively, and 32.7 and 27.0%, respectively, in women. CONCLUSIONS: MI cumulative incidence and mortality rates are low compared with other industrialized countries but, vary considerably among regions in a Mediterranean country like Spain.

[Myocardial infarction. Population case-fatality in seven Spanish autonomous communities: the IBERICA Study]. / Mortalidad poblacional por infarto agudo de miocardio. Estudio IBERICA.

BACKGROUND AND OBJECTIVE: The magnitude of the problem of myocardial infarction (MI) is better understood by assessing the population case-fatality than by analyzing only the number of patients attending hospitals. PATIENTS AND METHOD: Our data come from the IBERICA Study (Investigation, Specific Search and Registry of Acute Myocardial Ischemic Syndrome). Twenty eight-day MI population case-fatality is described in the population aged 25 to 74 years during 1997 and 1998 in the following Spanish autonomous communities: Castilla-La Mancha (Toledo and Albacete), Catalonia (Girona), Valencia Community (Valencia), Balearic Islands (Majorca), Murcia, Navarra and Basque Country. The relationship between case-fatality and other variables such as sex, age and geographic area is also analyzed. RESULTS: A total of 10,660 MI cases were registered, 4,106 of whom died within the period of 28 days following the onset of symptoms (38.5%; CI 95%, 37.6-39.4%). The overall case-fatality was 37.0% (CI 95%, 35.9-38.0%) in men and 44.3% (CI 95%, 42.3-46.4%) in women. Death occurred out of hospitals in 2,869 (69.9%) cases. An increased case-fatality in women was associated with a higher in-hospital case-fatality (45% higher than men). The proportion of patients who died before reaching a hospital was similar in both genders. Classical symptoms of MI were more common among men than women (82.7% vs. 77.6%, p < 0,001). The interval between symptoms' onset and hospitalization was 30 minute longer among hospitalized women as compared with men (p < 0,001). CONCLUSIONS: Population MI case-fatality is high in the seven Spanish autonomous communities studied. Approximately 2 out of 3 deaths occur without patients being able to reach a hospital. These results emphasize the importance of primary and secondary prevention measures and the necessity to design ready-access systems to defibrillation and resuscitation manoeuvres for patients with cardiopulmonary arrest.