Ischemic Heart Disease in German Immigrants and Their Descendants in a Region of Southern Brazil: A Comparison of Initial Symptoms Reported between two Generations

Background: Nothing is known about ischemic heart disease (IHD) in the Germans who emigrated to Brazil during the last century. Objective: We sought to compare age at diagnosis and IHD manifestations between German immigrants and their first-generation descendants in the region of Blumenau, Brazil. Methods: We reviewed medical records of hospitals in Blumenau. Comparison of the groups in the evaluation times was made by analysis of variance (ANOVA) with repeated measures, and comparison of two factors was made by two-way ANOVA. The level of significance was set at p <0.05. Results: Study population comprised 68 patients who were born in Germany (group G) and 99 descendants (group D). Twenty-nine patients of group D had two German parents and 70 had one. Mean age at diagnosis was 66.8 ± 10.6 years, with a significant difference between the groups, four years higher in Group G than group D (69.0 ± 8.8 vs 65.4 ± 11.5 years old) (p = 0.025). There was no significant difference in risk factors or coronary angiography data between the groups. HDL cholesterol levels were significantly higher in group G than in group D (48.4 ± 11.1 mg/ dL vs 43.3 ± 11.2 mg/dL, p = 0.005). Conclusion: At the time of first IHD diagnosis, mean age of the group G was significantly higher than group D, with no differences between groups in sex, risk factors, LDL levels, or clinical and angiographic manifestations. An earlier manifestation of the disease could be part of lifestyle changes in descendants, in this population that mantained eating habits characterized by high saturated fat consumption.

were above 400 mg/dL, calculation was performed using the standard lipid profile method. 19 LDL cholesterol levels were obtained at two time points (baseline and during treatment). Blood samples obtained during acute coronary events, regardless of whether the patient was already using lipid lowering agents, were not considered for analysis. HDL cholesterol levels were directly measured.

Statistical analysis
All variables were analyzed descriptively. Quantitative variables were expressed as mean and standard deviation. For qualitative variables, absolute and relative frequencies were calculated. The normality of the data was tested using the Kolmogorov-Smirnov test. 20 For comparison of means between two groups, the unpaired Student's t-test was used. 20 To test the homogeneity between proportions, the chi-square test 20 or Fisher exact test 20 was used. Comparison of the groups in the evaluation moments was made by analysis of variance (ANOVA) with repeated measures, 21 comparison of two factors was made by two-way ANOVA. 20 The statistical software used for the calculations was SPSS 21.0. The level of significance was set as 5%.
Sample size was not calculated because this retrospective study aimed to explore an existing and limited population in which all patients who were registered and attended cardiology services in the region were surveyed. They used the same strategy in a previous study comparing Japanese subjects and descendants (nisei) in Brazil 22 where we found a 10-fold greater probability of an early coronary event in Japanese descendants than in the Japanese group.

Results
A total of 299 records were obtained; 167 patients were included in the study and separated into two groups: group G, 68 patients (40.7%) who had emigrated from Germany, and group D, 99 patients (59.28%) born to German mothers and/or fathers. The other 132 subjects were excluded for the following reasons: a) not enough data were available in 80 records, b) no data related to IHD were available in 44 records, c) seven patients did not undergo coronary angiography and had no documented AMI, and d) one patient had only temporarily lived in the area (Figure 1) Studies around the world have explored the incidence and characteristics of ischemic heart disease (IHD) caused by coronary artery disease (CAD) in immigrants. For example, Japanese immigrants living in the USA or in Brazil, [4][5][6][7][8][9][10][11][12] Italians who migrated to Australia, 13 Norwegians, Finns, Germans and Hungarians who migrated to Sweden, 14 and Turkish immigrants living in Germany. 15 However, no previous study has assessed the German population and their first-generation descendants in Brazil to determine their risk factors for IHD. This would allow the implementation of health actions that would specifically promote good health to these populations. Additionally, such studies could identify changes from traditional habits that may have contributed to increased incidence of specific diseases. The aim of the study was to address relevant consequences of German migration to confined and specific areas in Brazil.

Methods
We performed a retrospective study of patients with IHD who reside in the Blumenau region. Data were collected from the medical records of hospitals and cardiology clinics in the region. Then we separated patients into two groups, G-Germans and D-descendants.
The diagnosis of IHD was made based on: a) a coronary angiography or a computed tomographic angiography for coronary anatomy showing at least one artery with a lumen obstruction of > 50% or b) the patient had experienced an acute myocardial infarction (AMI) that was confirmed by electrocardiographic criteria and/ or biochemical markers of myocardial necrosis.
Regarding the clinical data, the time of onset of CAD was defined as the date of the first presentation of IHD recorded in the medical record and/or presence of AMI or angina pectoris. Angina was classified according to the criteria of the Canadian Cardiovascular Society (CCS); 16 sex and age on the date of the first symptoms were recorded. Diabetes was defined as the use of oral antidiabetic drugs or insulin, and hypertension was defined according to the ESH/ESC Guidelines for managing arterial hypertension. 17 We determined whether the patient was a smoker at the time they were diagnosed and identified former smokers those who quit smoking at least five years before, and nonsmokers as those who had never smoked. 18 Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald formula. In cases in which triglyceride levels There was no significant difference in sex, smoking status, hypertension, or diabetes between the groups.
However, when we divided the populations using age cutoff values for CAD risk 23 of 55 years for men and 65 years for women, we found significantly older people in group G than in group D ( Table 1). No data regarding smoking were found in seven subjects and no data regarding arterial hypertension were found in two subjects.
There was no significant difference between groups in the occurrence of AMI with or without ST segment elevation, Canadian Cardiovascular Society class of angina, or presence of angina. The first manifestation of IHD was AMI in 72 (43.4%) of all patients: 39 (39.8%) in group D and 33 (48.5%) in group G. Of those with AMI, 67 (93.1%) displayed ST elevation, 35 (89.7%) in group D and 32 (97%) in group G. No data were obtained regarding AMI in one subject and regarding angina in three subjects (Table 2).
Baseline LDL values were 159.0 ± 48.9 mg/dL in group D and 157.4 ±42.9 mg/dL in group G, and this difference was not statistically significant (p = 0.355). When we compared baseline and post-treatment cholesterol measurements between the groups, no statistically differences were found (Table 3). HDL levels, however, were significantly higher in Germans than in descendants (48.4 ± 11.1 mg/dL vs. 43.3 ± 11.2mg/ dL; p= 0.005). No data regarding HDL levels were available in 13 patients. Mean age of all patients at IHD diagnosis was 66.9 ± 10.6 years old (range, 40-90 years old); 65.4 ±11.5 years old in group D, and 69.0 ± 8.8 years old in group G. The difference was statistically significant (p=0.025), four years on average, as shown in Figure 2 as a normal curve and a cumulative normal curve.
We then sought to determine whether there were associations between age at diagnosis and gender or initial symptoms. We found significant differences by age and sex groups (Table 4). We also evaluated differences in age at diagnosis among descendants according to ancestry, and found that in the 70 descendants with only one German parent, mean age was 64.2 ± 11.9 years old, and in the 29 descendants with two German parents, mean age was 68.3 ± 11.3 years old (p = 0.02).
We did not observe any interaction between age at diagnosis and initial symptoms by sex or other variables (p = 0.574), including interaction between the class of angina and age at diagnosis with IHD.

Discussion
Previous studies have examined populations that emigrated from other countries to countries in the Americas. This study is the first to explore IHD in German immigrants living outside their country of origin in a confined area in Brazil. This allowed the evaluation of IHD manifestations in German immigrants and their descendants without a strong cultural interference.
An important difference observed between Germans and their descendants was age at the time of the first diagnosis of IHD symptoms. Mean age was four years higher in the first generation of immigrants compared as descendants, even though both populations may have maintained their eating habits and other habits of life.
There was no difference in other IHD characteristics, such as coronary anatomy and disease extension, or the occurrence of AMI with or without ST segment elevation. We did not observe differences between the groups in the incidence of systemic arterial Probably we did not find the same results because our population was concentrated in Blumenau area without major external interferences. Blood test results were also similar, except for HDL cholesterol, which was higher in Germans than their descendants.
Except for the differences we observed in HDL cholesterol levels and age at the first manifestation of disease, no other variable was different in the univariate analysis, so we did not perform a multivariate regression. Such analysis would be justified if we wanted to correct for a confounding factor. We used the analysis of variance of two factors (sex and age) when    There are some limitations needed to be addressed. First, in the region of Blumenau, where this survey was performed, periodic floods occur because of intense rains that overflow the rivers. Hence, many patient records were missing, and for this reason, we were unable to include in this cohort a larger number of cases, especially those related to patients who originated from Germany. 25 Second, the number of patients were small, despite representative of Blumenau population. Third, not all data were available from the medical records of patients, which is seen the variation of "N" in the tables. Finally, we do not know the age of patients who died from AMI, and therefore we do not know whether Germans died at an early age or had a higher prevalence of cardiovascular risk factors.

Conclusion
Mean age at the first diagnosis of IHD was four years higher in German immigrants than in the firstgeneration descendants. German patients had higher HDL-cholesterol levels, which may be explained by the fact that these individuals did more legwork than their descendants.

Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.

Sources of Funding
There were no external funding sources for this study.

Study Association
This article is part of the thesis of Doctoral submitted by Sergio Luiz Zimmermann, from Universidade de São Paulo -INCOR.

Ethics approval and consent to participate
This article does not contain any studies with human participants or animals performed by any of the authors.