Epidemiology of coronary heart disease risk factors in a free-living population

PREVENTIVE

MEDICINE

8,

Epidemiology

445-462 (1979)

of Coronary Heart Disease Risk Factors in a Free-Living Population

Jo& NEUMAN,MARIA P. DE NEUMAN,ELINAVALERO,AND

DANIELLINDENTAL Department of Preventive Medicine, Instituto de Obra Social de1 Ejercito (IOSE), Buenos Aires, Argentina A project for the detection and treatment of multiple risk factors (MRF)for coronary heart disease (CHD) has been initiated in Argentina. After complete medical and routine laboratory studies, 462 apparently normal subjects were found. The prevalence of RF was: hyperlipoproteinemia (HLP) 43.9%. hypertension (2 160-95) 17.3%, smoking habits 35% (heavy smokers 7.%), psychosocial stress 49.5%, overweight (weight/height > 1.10) 40.3%, sedentary habits 44.8%, family history of CHD lo.%, diabetes 6.%, and minor electrocardiographic abnormalities 6.6%. The distribution of the different types of HLP showed that type IV, with a frequency of 21.%, was the most common. Types IIa and IIb had a prevalence of 1I.5 and 10.6%, respectively. An extra pre-P band was detected in 25% of the population. Striking sex differences were found. Both type IV HLP prevalence and serum uric acid levels were significantly higher (P < 0.001) in males than in females. On the contrary, sedentary habits and psychosocial stress were significantly more prevalent in women than in men (P < 0.001). RF associations have been demonstrated between type IV HLP, overweight, hypertension, tobacco smoking, and diabetes. RF prevalence tended to increase with advancing age with the exception of smoking habits. In this apparently normal population, 36.9% of the men and 19.4% of the women had two or more major risk factors requiring treatment because of their high CHD risk.

INTRODUCTION In Argentina, a project for the detection and treatment of multiple risk factors (RF) for coronary heart disease (CHD) and atherosclerotic sudden death (ASD) has been initiated by an organization which provides social and medical care to tens of thousands of civil workers in the Army and some military men and their families throughout the country. In this epidemiological approach to preventive medicine, the health status of this population is assessed through a medical and biochemical survey. To date, 780 subjects have been screened of whom 452 are apparently normal. In this paper the prevalence of risk factors in this apparently overtly normal population of 462 individuals is discussed. MATERIAL AND METHODS Baseline Studies Complete medical history and physical examination, blood pressure readings, standard 12 lead electrocardiogram, chest x-ray, ophthalmoscopic examination, vital capacity, and relative weight determination. Laboratory Measurements Twenty milliliters of venous blood were drawn from each participant after a 12to 14-hr overnight fast. One aliquot was collected in a tube containing EDTA (1 mg/ml) for lipid determination and the remainder was used for determination of 445 0091-7435/79/040445-18$02.OWO Copyright @ 1979 by Academic Press. tnc. All right’s of reproduction in any form reserved.

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blood sugar, blood urea, serum uric acid, red cell count, hematocrit, hemoglobin, white cell and differential count, sedimentation rate, serum transaminases (SGOT and SGPT), VDRL, and prothrombin time. Standard urinalysis was also performed. Plasma lipid determinations were made, consisting of: total cholesterol, using the method of Rappaport and Eichhorn (50); triglycerides, using the enzymatic method of Eggstein and Kreutz (13); and lipoprotein fractions, using agarose gel electrophoresis, a slight modification of the Noble method (43). Electrophoresis was performed within 24 hr after blood extraction to detect extra pre-p bands. One normal plasma sample was always obtained in each electrophoretic test for visual comparison of the bands and to estimate qualitative variations of low (LDL), very low (VLDL), and high (HDL) density lipoproteins. In previous studies, the results obtained by the Rappaport and Eichhom method for total cholesterol compared well with other reported data on cholesterol distributions. Criteria for Lipoprotein Normal. Cholesterol

Typing

and triglyceride levels up to 250 and 150 mg/lOO ml, respectively; on electrophoresis neither a chylomicron band at the origin nor prominent p or pre-P bands. Type ZZa. Plasma cholesterol above 250 mg/lOO ml and /3 bands of the electrophoretogram more intensely stained than normal. Normal triglyceride levels and normal pre-/3 band. Type ZZb. Elevated cholesterol and triglyceride plasma levels. A prominent p band and pre-/3 more intensely stained than the normal pattern. Type IV. Normal or moderately elevated cholesterol levels, normal /3 band, triglyceride levels greater than 150 mg/lOO ml and a prominent pre-p band. The formula LDL = total cholesterol - (triglyceride/5 + HDL) was applied to differentiate type IV from type IIb in some intermediate states. For practical purposes, HDL cholesterol was considered 45 mg/lOO ml (32). Results above 190 mg/lOO ml were indicative of type IIb, hyperlipoproteinemia. The population under survey can be considered typical of urban middle class people, most of whom are physically inactive and are burdened with everyday worries and tensions. They include employees, executives, technicians, professionals, and housewives. The Department of Preventive Medicine Program attracted people because of the complete free checkup and our interest in studying individuals in good health. The results herein reported were obtained from consecutively examined persons over a period of 1.5 years. Norma; people were considered those without history, symptoms, or signs of heart disease or other complaints and without manifestations of vascular disease or known arterial hypertension before the examination. Included in this group were those hypertensive subjects detected in this screening and persons with minor ST segment and T wave changes, slight intraventricular conduction defects or benign transitory arrhythmias. Ischemic cardiovascular diseases and atherosclerotic events were defined by a history of angina1 pain, myocardial infarction, stroke, transient ischemic attacks, intermittent claudication and, in some cases, electrocardiographic diagnosis including ergometry.

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RISK FACTORS: DEFINITIONS Hyperlipoproteinemia. Plasma total cholesterol and triglyceride levels above 250 and 150 mg/lOO ml, respectively, were considered to be elevated. Lipoprotein typing was done according to the WHO Bulletin (2), as described below. Arterial hypertension. Two consecutive measurements were taken after 5 min in the supine position. The point when sounds ceased was recorded as the diastolic blood pressure. The initial measurement was the basis for classification. The procedure was subsequently repeated when it showed arterial hypertension (defined as two or more readings for systolic blood pressure 160 mm or over), or diastolic blood pressure 95 mm or over (WHO criteria). Blood pressure was measured with mercury sphygmomanometers in the right arm and diaphragm stethoscopes. Tobacco smoking. Smoking was categorized by number of cigarettes: up to 10, 11-19, and 20 or more cigarettes per day (heavy smokers). Diabetes. Fasting serum glucose, over 120 mg%. Borderline individual cases (above 100 mg/lOO ml) were confirmed by the glucose tolerance test. Curves were considered to be abnormal when the peak value exceeded 160 mg/lOO ml and/or 2-hr levels were higher than 120 mg/lOO ml. Overweight. Overweight was defined as degree of relative weight (rw) above 1.10 or 1.20 measured with the weight/height index (weight in kg divided by height in cm minus 100). Sedentary habits. Minimal physical activity was defined by no manual work, exercise or sports, and walking less than 20 blocks daily. Psychosocial stress. A standard questionnaire was used to determine the existence of anxiety situations, personality or family troubles, and/or psychiatric history. People with some major occupational, socioeconomic, or psychological problems in their lives sufficient to disturb their emotional equilibrium were classified as having psychosocial stress. Family history. Persons with parents who had atherosclerotic events prior to age 50. Major risk factors. MRF in this survey: arterial hypertension, hyperlipoproteinemia, heavy cigarette smoking, and diabetes were considered as MRF. Statistical methods. Significance of the difference between means and proportions was obtained from t and x2 tests, respectively. Probability (P) was considered significant at values of 0.05 or smaller (p s 0.05). RESULTS Age and Sex Of the 780 subjects screened, 462 were apparently normal as previously defined (230 men aged 15-78 years and 232 women aged 15-83 years). Figure 1 shows the distribution of this population by age and sex; 63.9% of the people (295/462) were between 41 and 60 years old. Hyperlipoproteinemia (HLP) Prevalence of HLP was 43.9% in the apparently healthy population. Type IV was the most prevalent (21.9%) compared with 11.5 and 10.6% for types IIa and IIb, respectively. No subjects with types I, III, or V HLP were detected. Males

448

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FAO

2l30

ET

B-LO

AL.

W-Y) Sk60

61-70 > 70 years

FIG. 1. Distribution

of subjects by age and sex.

showed a significantly higher prevalence of HLP than females, in a ratio of 54.3 to 33.6%. Differences between the sexes were due to the higher prevalence of type IV in males than in females (30.4 vs 13.4%). However, there were no sex differences for types IIa and IIb (Table 1). Type IV patterns were more frequent in men than in women at all ages, particularly in those individuals over 30 years of age. Type IIa HLP showed a higher prevalence in women than in men in the sixth decade (19.7 vs 9.6%) (Fig. 2). Type IIa HLP was absent in females at ages 15-20, compared with a frequency of 16.7% in males of the same age; but the number of young subjects is small. Men presented more type IIb patterns in the fifth decade, while females in the sixth decade showed a striking increase in all types of lipoprotein patterns encountered, compared with younger groups (Fig. 2). Plasma cholesterol levels in men rose gradually with advancing age, showing the highest values between 41 and 70 years and then declining; cholesterol levels in women peaked during the sixth decade (Table 2). Significant sex differences TABLE PREVALENCEOF

H~PERLIPOPROTEINEMIA

Females

Type

Males (230)fl (960) 11.7 12.2 30.4 54.3

11,

I&l IV Total U Number of subjects.

I

PATTERNSAMONG"NORMAL"POPULATION

Cm

Statistical significance

Both sexes (462)

m’u)

P

mJ)

11.2 9.0 13.4 33.6

NS NS
11.5 10.6 21.9 43.9

449

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T FEMALES

MALES N

YEARS

OF AGE

FIG. 2. Prevalence of hyperlipoproteinemic

patterns among population by age and sex.

TABLE PLASMA

Age range (years) 15-20

CHOLESTEROL

-

TRIGLYCERIDE

Females

209 + 38”

195 k 27

1% + 33

41-50

250 c 44

231 k 39 (75)

>70

245 2 43 (83)

258 + 42

255 _f 49

249 r 54

234 -i- 47 (10)

Males

Females

88 5 35

96 + 39

90 r 46

100 5 44

150 + 70

109 + 41

co.05

169 + 82

112 t 51

10.001

170 + 108

141 t 72

co.05

162 k 81

137 f 45

P

(26) 214 k 35 (25)

(25)

Pii

200 k 36

236 + 35 (24)

61-70

POPULATION

(6)

31-40

(66)

FOR “NORMAL”

Triglycerides (mg/lOO ml)

Males

(16)

51-60

2 LEVELS

Cholesterol (mg/lOO ml)

(6)’ 21-30

AND

-co.01

(71)

(21) 231 k 28

134 k 53

138 + 89

(7)

n Significance between sex (t test). L Mean 2 standard deviation. (( Number of subjects in which cholesterol and triglycerides were determined.

* Significance ** P < 0.01. ***p < 0.001.

of difference

154 26 21 31

28 69

IIb IV

Females Normolipemic 11, IIb IV

27

106

11,

Males Normolipemic

No.

between

8.4 23.1 14.3 38.7***

25.0 21.7

11.1

19.8

proportions

19.5 19.2 19.0 16.1

17.9 23.2

33.3

21.7

against

TABLE

3

group:

1.9 11.5’; 9.5” 9.72:

10.7 17.4**

7.4

3.8

Diabetes

NORMOLIPEMIC

normolipemic

10.4 23.1 33 3** 48 4***

32.l** 30,4***

14.8

10.4

>I.20

AMONG

Obesity

FACTORS

>I.10

(‘36) OF RISK

Hypertension

PREVALENCE

10.4 7.7 14.3 6.5

17.9 18.8

25.9

14.1

>lO

Cigarette

1.3 0 4.8 3.2

17.9 20.3*

11.1

9.4

>19

smoking

HYPERLIPOPROTEINEMIC

P < 0.05.

AND

64.9 69.0 57.1 64.5

46.4 56.5

29.6

46.3

Sedentary habits

SUBJECTS

61.0 65.4 71.4 48.4

44.9 32.1

37.0

42.4

Stress

10.4 11.5 19.0 19.3

14.3 10.1

11.1

8.5

Family history

P

z

z

z

z

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were absent except in the fifth decade where cholesterol concentration was significantly higher (P < 0.01) in males than in females. Women in the age range of 5’1-60 years showed higher cholesterol’levels than men, but the diierence was not significant. Plasma triglyceride concentrations were elevated significantly in males compared with females in the fourth, fifth, and sixth decades (Table 2). Obesity (weight/height index greater than 1.20) was more prevalent among persons with type IV and type IIb HLP (P < 0.001 and P < 0.01, respectively) than among their normolipemic counterparts (Table 3). Male heavy smokers predominated (P < 0.05) in type IV HLP (Table 3). Hypertension was more common in hyperlipemic females than in males; the difference was significant in type IV. Diabetes was significantly more prevalent among men than women in type IV, and among women in types IIa, IIb, and IV (Table 3). An extra pre-/3 band was observed in the electrophoretic strips in 25% of the total population. Sex was not a significant factor. Arterial

Hypertension

Arterial hypertension was present in 17.3% of the total population (Fig. 3) and in 1% of the population between 41 and 60 years (56/295). Prevalence was slightly higher for males than females: 20.1% (30/149) vs 17.8% (26,046). High blood pressure, as previously defined, appeared in the fourth and fifth decade in men and women, respectively. Hypertension was more frequent in men until the fifth decade and then became more common in women (Fig. 4). Hypertension was significantly associated with HLP in women and with overweight in both sexes at ages 41-60 years (Fig. 5).

50

r 44.8 -

40.3 193

>I2

2l 1.10 6.5

FIG.

3. Prevalence

of risk factors

for CHD

;I

in a free-living

population

of 462 “normal”

people.

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Cigarette Smoking Thirty-five percent (Fig. 3) of the population smoked cigarettes, 7.9% being heavy smokers. Men smoked significantly (P < 0.001) more than women (13.9 vs 1.8%), the proportion decreasing in both sexes with age (Fig. 4). Diabetes Diabetes prevalence rose with advancing age after the fourth and fifth decade for men and women, respectively (Fig. 4). Diabetes was diagnosed in 13 cases (2.8%). In another 19 persons (4.1%), suspected diabetes was confirmed by oral glucose tolerance test. Thus, the prevalence in the total population was 6.9%. Prevalence was higher in males than in females (9.1 vs 4.7%, nonsignificant).

FIG,

4. Prevalence

of risk factors

by age and sex.

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STUDY IN ARGENTINA

453

NORMOTENSIVES HY PERTENSIVES MALES

:EMALES

FIG. 5. Prevalence of risk factors for CHD in a group of 56 hypertensive and 239 normotensive subjects aged 41 to 60 years.

Overweight of the total population, 40.3% presented with a relative weight over 1.10 (Fig. 3); in 19.3%, the index was over 1.20. Overweight (>l. 10) rose with age from the fourth decade in both sexes (Fig. 4). Total prevalence among males and females was 42.6 and 37.%, respectively. Serum Uric Acid Males showed significantly higher levels (4.1 5 1.0 mg%) than females (3.2 t 0.9 mg%) (P < 0.001) (Table 4). Only 1.7% of the men and 0.4% of the women had levels of 6.5 mg% or more. Gouty arthritis was detected in 1.1% of the population. Sedentary Habits Sedentary habits (Fig. 3) showed a total prevalence of 44.8%, with significantly more frequency (P < 0.001) in women (57.3%) than in men (32.2%). This difference was observed in every decade (Fig. 4). Psychosocial Stress Emotional stress derived from occupational, economic, or personal problems appeared in 49.5% of the group (Fig. 3). Women showed a significantly (P < 0.001) greater frequency than men (58.2 vs 40.9%).

NEUMAN

454

ET AL.

TABLE 4 MEAN SERUM URIC ARID LEVELS (mgi100 ml) IN “NORMAL” Age range (years)

No. of subjects

15-20 21-30 31-40 41-50 51-60 61-70 >70 Total

6 16 24 66 82 25 10 229

Males 3.8 3.8 3.9 4.2 4.2 4.1 3.8 4.1

+ k -t + + f k 2

0.8” 0.5 1.0 1.0 1.1 0.9 1.0 1.0

No. of subjects

POPULATION Females

6 27 25 75 70 21 7 231

3.2 3.2 3.2 3.1 3.5 3.0 3.5 3.2

P”

t 0.4 2 0.9 k 0.9 L 0.8 k 0.9 Tk 0.9 ? 1.1 t 0.9

CO.02 ‘Co.02
fl Significance between sex (r test). BMean ? standard deviation.

Family History

Family

history was positive in 10.9% of the subjects (Fig. 3).

Electrocardiographic

Changes

In these apparently normal people, 5.5% had bundle branch block or left anterior hemiblock (Table 5). Total prevalence, including minor repolarization, ST or T wave changes, was 6.6%; 4.5% had isolated premature ventricular or atrial premature beats or sinus tachycardia. One man had an episode of paroxysmal atria1 fibrillation. Population at Risk

(Fig. 6). Of those with major risk factors, 44.3% of the men had only one MRF, 30% had two MRF, 6.9% had three or four MRF; among women, the corresponding frequencies were: 34.9, 15.5, and 3.9%. In the total population, only 6.9% of the females and 5.2% of the males had none of the MRF and none of the other RF investigated in this study. DISCUSSION Epidemiology and Risk Factors for Atherosclerotic

Retrospective

studies have demonstrated

Cardiovascular Disease

the association

between risk factors

TABLE 5 ALTERATIONS OF THE ELECTROCARDIOGRAM IN APPARENTLY “NORMAL”

PEOPLE

No. of persons

Right bundle block Left bundle block Left anterior hemiblock Premature ventricular beats Premature atria1 beats Sinus tachycardia Atria1 fibrillation

Male

Female

6 1 11 6 4 3 1

3 4 3 1 2 -

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r 44.3

1 MRF P< 0.05 FIG. 6. Prevalence

0

MALES

2 MRF - ~---. PC 0.001 of major

risk factors

3OR4 MRF (MFR)

in the “normal”

WITHOUT MRF PC ox)01 population.

and atherosclerotic diseases. Prospective studies (30, 52) have shown the possibility of predicting morbidity and mortality, including atherosclerotic sudden death (ASD), in terms of the major risk factor combinations (18, 20, 28, 31). The coronary risk profile (11, 42) and knowledge of plausible mechanisms of action of the RF (1, 16, 61) are in keeping with demonstrations in experimental animals (62) and humans (65). RF are difficult to change (9), but in spite of criticism (59), some results are encouraging (58) and suggest that RF detection is advisable as early as possible (19,48). Many primary prevention trials are in progress in different parts of the world (56). In secondary prevention, the problem of identifying and treating individuals susceptible to ASD (12) has not yet yielded results (34). Community surveillance for CHD (35, 53) can provide data on the results of the intervention programs. Hyperlipoproteinemia The high prevalence and the remarkable sex difference of type IV HLP found in this study is similar to previous results (5, 63). To compare data obtained from different populations, age and sex distribution, as well as criteria applied for lipoprotein typing must be taken into account. We chose the study by Brown et al. (5) for comparison as the upper limits for cholesterol and triglycerides were in accordance with those used in our study, although the age ranges were not similar. Thus, these authors reported a frequency of 37.4% of type IV HLP in males aged 35-44 years which is quite close to the prevalences of 37.5 and 33.3% in males aged 31-40 and 41-50 years, respectively, found in the present study. The striking sex difference in type IV HLP observed in this study for the

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population aged 3 l-50 years tends to decrease in older age groups. Females aged 51-60 showed a higher prevalence of this disorder compared with younger women. Types IIa and IIb HLP were also more common in the 50s and older, suggesting that hormonal disturbances strongly influence plasma lipid levels. A high prevalence of obesity was found in types IV and IIb HLP for both sexes at weight/height indices greater than 1.20. Heavy smoking was associated with type IV patterns in men; the increased release of free fatty acids by nicotine (29) could be the mechanism involved. Hypertension was also found to be significantly more prevalent in type IV HLP females, and diabetes showed a greater frequency in hyperlipemic subjects compared with normolipemics. Arterial Hypertension Hypertension is associated with an increased incidence of coronary, cerebrovascular (26), or occlusive arterial diseases (44). Its reduction diminishes cardiovascular mortality and morbidity (44,56, 58). The total prevalence of hypertension in this population (17.3%) is comparable with other American and European surveys (23, 27, 55). Palmer0 obtained 10% prevalence of arterial hypertension in Cordoba, Argentina (49). It is important that our blood pressure readings are casual and do not always remain high in successive determinations. Labile hypertension represents a large segment of the population initially identified as having hypertension (7). The association of hypertension with other RF, especially with HLP and obesity (Fig. 5), is clearly shown in this population and is evident in other reports (27). Cigarette Smoking Our results do indicate the great prevalence of cigarette smoking as a RF. Heavy smokers accounted for only 7.9% of this apparently normal group, which is lower than values reported elsewhere (57). Smoking exerts an influence in each sex and age group and relates an increasing number of cigarettes smoked to an increasing risk of CHD (51, 60). Cigarette smoking, added to hypertension and/or hyperlipoproteinemia, seems to have the strongest influence on the development of cardiovascular disease or ASD. In our study, the number of cigarettes smoked was significantly less (P < 0.001) in women and decreased with increasing age. There is suggestive evidence that cessation of smoking can reverse the risk; other projects will provide more data about this possible benefit (22). Diabetes Mellitus and Chemical Diabetes Diabetes and glucose intolerance are considered independent RF for CHD (14, 21). In aged people, the risk for myocardial infarction was twice as high in diabetic men and three times as high in diabetic women as in the nondiabetics (33). In our population, the prevalence figures were similar to those reported by others; we also found a highly significant increase in serum p-glucuronidase in patients with either clinical or chemical diabetes which may indicate atherogenic traits (40, 41). Nevertheless, a low frequency of CHD was found in the Honolulu study, despite the fact that Japanese men had an unusually high prevalence of glucose intolerance (25).

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Overweight Obesity increases the risk for CHD, primarily because of its association with hypertension, hyperlipoproteinemia, tobacco smoking, sedentary habits, and diabetes (52). The influence of relative weight as an independent RF was much weaker in Framingham than in Honolulu or Puerto Rico where Kagan and his colleagues (25) found a strong association with CHD incidence. The prevalence of obesity in our population is similar to that reported by others (57). Our results support the hypothesis of hormonal protective action, showing a lower prevalence of HLP in females than in men in spite of their higher relative weight and more sedentary lifestyle. Serum Uric Acid Levels The results obtained with the method used (6) confirm the known significant differences between the sexes and the insignificant change with age. In the Honolulu study (25), using univariate and multivariate analyses, uric acid levels of 6.5 mg/lOO ml or more were associated with increased CHD risk. Similar results were found in Framingham, with a twofold increase of risk in gouty arthritis. Our results showed lower mean levels of serum uric acid than reported by Kagan and colleagues using a different method, in Japanese men in Japan, Hawaii, or California (42). Extra Pre-/3 Band This band was observed in the stained agarose electrophoretic strips of population with a similar frequency to that reported by Carlson and colleagues who identified it with the “sinking pre-0.” Further studies will determine significance of this band in connection with atherosclerotic disease as a RF CHD.

our (8) the for

Sedentary Living The poor physical activity of our population is characteristic of that in almost all large urban areas. The data on physical activity and CHD are contradictory but tend to support the thesis that activity is protective and that lack of it is a risk factor in economically developed countries. Relationships between physical inactivity, CHD frequency, and elevated RF have been observed (37, 46). In this population, physical inactivity among women antedated sedentary habits in men (Fig. 4); this trend could contribute to the genesis of other RF like overweight in young women as observed in our study. Psychosocial Tensions Our population, especially females, exhibited a high prevalence of emotional tensions. The frequency of this tension is not comparable with other investigations, as the methods of measurement differ and are difftcult to standardize. Premature atherosclerosis is a feature of the 20th~century lifestyle (56), including habits of overeating, high fat diets, tobacco smoking, sedentary habits, and psychological or socioeconomic stress. Personality types (4) and special circumstances [geographical mobility, urbanization, social status, life events, marital status (33), occupation, etc.] can predispose to CHD. “Sociophysiology” attempts

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to explain the neural or hormone mechanisms, pathways, and interrelation involved in the correlation of stress with acute events and the possible role of stress in chronic aiIments (24, 64). Family

History

Atherosclerotic events in close relatives up to 50 years of age or other manifestations of cardiovascular disease in the family are considered as RF (17). Neufeld considered anatomic differences in the coronary arteries intima, in the first months or years of age, as genetically determined (39). Hyperlipoproteinemia can already be detected in umbilical cord blood (35). However, more importance is given today to the environment, as shown by twin studies, migrations, or secular changes (15) in prevalence of CHD. There are families in which vulnerability to CHD can be due to defined reasons: the same diet, smoking habits, or familial aggregations of hypertension, diabetes, or hyperlipoproteinemia (15, 17, 52). Abadal and colleagues (57) used different criteria from ours (parents and/or brothers with diabetes, hypertension, and atherosclerotic events prior to age 70) and reported a prevalence of a positive family history as high as 40% in people from a factory in Manresa (Spain), Two hundred ninety-five subjects, most of the people in this study, were 41 to 60 years of age (Fig. 1). CHD in adults within the United States starts to increase from age 25 and reaches a maximum at 55 to 74, a great proportion of events occurring under the age of 65. Nevertheless, there are many documented autopsies and clinical reports of lesions at younger ages (36). Therefore, atherosclerosis can also be considered a pediatric problem. The adult populations of developed countries have the highest CHD rates. However, death rates in the United States have been declining in the last few years (31). In our population, as in all others, most RF tend to increase with advancing age, the most remarkable finding being that HLP frequency peaks in women two decades later than in men. Obesity and sedentary habits are fully established at an earlier age. Risk factors are increased in older people with myocardial infarction, especially in women who show a significant increase of systolic and diastolic blood pressure and of plasma cholesterol (33). Moreover, complications occurring after coronary events, including ASD, increase with age in an exponential form (38). Sex Women are protected against CHD during their mature years possibly because of endocrine factors (56), although estrogen administration does not prevent recurrences (10). Moreover, administration of this hormone may cause thromboembolism. In a review of the possible reasons for the comparatively high resistance of women to heart disease, Seely (54) speculates on the role of menstrual hemorrhages. In our study, the fact that mature women presented lower triglyceride, lower uric acid levels, and less frequency of type IV HLP could be important. In spite of this protection, the rate of CHD in young women is increasing (45), possibly due to the increase in tobacco smoking, contraceptive pill use, and, as

CHD RISK FACTOR STUDY IN ARGENTINA

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observed in our female population, the high frequency of stress, sedentary habits, and obesity. In the BaItimore study (X), a higher incidence of CRD was found among men than among women in blacks and whites. In men, higher mean triglycerides and systolic blood pressure levels, more coexistence of RF, and a tendency to have larger increases in mean levels of the variables with age probably contribute to greater male susceptibility to ischemic heart disease (47). Bencze (3) considered the presence of serious disturbances in the enzymatic and hormonal regulation of the vascular system in the vulnerable white male subgroup to be of more importance than an estrogen-mediated protective effect in the female. In aged people there were no significant differences in the incidence of MI between sexes (33). Electrocardiographic

Changes

Normal people may have ST depressions less than 0.1 mm or slight T-wave abnormalities, but prospective studies have found a higher incidence of CHD for persons with those characteristics. Several studies, including our own, have found conduction disturbances, bundle branch block, hemiblocks, and paroxysmal arrhythmias, or sinus tachycardia among clinically normal people. Argentina requires a special investigation for Chagas disease in every person with conduction disturbances. Left ventricular hypertrophy is considered a key RF. Population at Risk

In our population, 18.8% of the men and 45.7% of the women had no MRF. This may explain to a large extent the protection of women against CHD. Our data are similar to those on men included in the “Pooling Project” in which 17% had no MRF (56). In our study (Fig. 6), 36.9% of the men and 19.4% of the women had two or more MRF; the corresponding figure for men, based on Pooling Project data, defining smoking as any use of cigarettes, was 38% (56). Stamler has calculated the presumed effect of preventive measures in the male population if they are applied to those with two or more MRF (27). If this is used as the criterion for selecting persons at highest risk and in particular need of preventive treatment, approximately one-third of the men and one-fifth of the women in our population would require such protection. If a single risk factor was to be considered a criterion, four-fifths of the men-essentially the entire adult male populationwould be eligible for active intervention. ACKNOWLEDGMENT We wish to thank Professor Dr. F. H. Epstein for his helpful criticism and advice in the preparation of the manuscript.

REFERENCES 1. Astrup, P. A. Tobacco smoking and coronary disease. Acta Cardiologica Suppl. 20, 105-117 (1974). 2. Beaumont, J. L., Carlson, L. A., Cooper, G. R., Fejfar, Z., Fredrickson, D. S., and Strasser, T. Classification of hyperlipidemias and hyperlipoproteinemias. Bull. WHO 43, 891-915 (1970). 3. Bencze, W. L. “Hypolipidemic Agents” (D. Kritchevsky, Ed.), Springer-Verlag, Berlin/New York, 1975.

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4. Brand, R. J., Rosenman, R. H., Scholtz, R. I., and Friedman, M. Multivariate prediction of coronary heart disease in the western collaborative group study compared to the findings of the Framingham study. Circulation 53, 348-3.55 (1976). 5. Brown, D. F., and Daudiss, B. S. Hyperlipoproteinemia. Prevalence in a free-living population in Albany, New York. Circulafion 47, 558-566 (1973). 6. Caraway, W. T. Determinations of uric acid in serum by a carbonate method. Amer. J. C/in. Putho/. 25, 840-845 (1955). 7. Carey, R. M., Reid, R. A., Ayers, C. R., Lynch, S. S., McLain, W. L., and Darracott, V. E. The Charlottesville blood pressure survey. JAMA 236, 847-851 (1976). 8. Carlson, L. A., and Ericsson, M. Quantitative and qualitative serum lipoprotein analysis. Atherosclerosis 21,4!7-433 (1975). 9. Cohn, K., Sakai, S. J., and Langston, M. F. Effect of clofibrate on progression of coronary disease: A prospective angiographic study in man. Amer. Heart J. 89, 591-598 (1975). 10. Coronary Drug Project Research Group. Factors influencing long-term prognosis after recovery from myocardial infarction, three-year findings of the Coronary Drug Projects. J. Chron. Dis. 27, 267-285 (1974). 11. Prepared by Committee on Reduction of Risk of Heart Attack and Stroke. “Coronary Risk Handbook.” American Heart Association, New York 1973. 12. Doyle, J. T. Profile of risk of sudden death in apparently healthy people. Circulation 52(Suppl. III), 176- 179 (1975). 13. Eggstein, M., and Kreutz, F. H. Eine neue bestimmung derneutralfette im blutserum und gewebe. Klin. Wechenschr. 44, 262-267 (1%6). 14. Epstein, F. H. Hyperglycemia: A risk factor in coronary heart disease. Circulation 36, 609-619 (1967). 15. Epstein, F. H., and Krueger, D. E. The changing incidences of coronary heart disease. Mod. Trends Cardiol. 2, 17-35 (1969). 16. Epstein, F. H. Intolerancia a la glucosa y enfermedades Cardiovasculares. Triangulo 12, 3-8 (1975). 17. Epstein, F. H. Risk factors in coronary heart disease, Environmental and hereditary influences. hr. J. Med. Sci. 3, 594-607 (1967). 18. Friedman, G. D., Klatsky, A. L., and Siegelaub, A. B. Predictors of sudden cardiac death. Circulation 52(Suppl. III), 164-169 (1975). 19. Goldstein, J. I., Albers, J. J., Hazzard, W. R., Schrott, H. G., Brerman, E. L., and Motulsky, A. G. Genetic and medical significance of neonatal hyperlipidemia. J. C/in. Invest. 52, 35a (1973). 20. Gordon, T., Garcia Palmieri, M. R., Kagan, A., Kannel, W. B., and Schiffman, J. Differences in cqronary heart disease in Framingham, Honolulu and Puerto Rico. J. Chron. Dis. 27,329-344 (1974). 21. Hayner, N. S., Kjelsberg, M. O., Epstein, F. H., and Francis, T. Carbohydrate tolerance and diabetes in a total community. Tecumseh, Michigan. Diabefes 14, 413-423 (1965). 22. Holmes, W. L. “Multiple Risk Factor Intervention Trial,” presented at the IVth International Symposium on Atherosclerosis, Tokyo, Japan. August 1976. 23. Hypertension Detection and Follow-up Program, in “CVD Epidemiology Newsletter” (N. 0. Borhani, Ed.) No. 20, p. 53, January 1976. American Heart Association, New York. 24. Jenkins, C. D. Factores de riesgo psicologicos y sociales de la enfermedad coronaria. Orientation Medica 26, 493-503 (1977). 25. Kagan, A., Gordon, T., Rhoads, G. G., and Schiffman, J. C. Some factors related to coronary heart disease incidence in Honolulu Japanese men: the Honolulu heart study. Inr. J. Epidemiol. 4, 271-279 (1975). 26. Kannel, E. Current status ofthe epidemiology ofbrain infarction associated with occlusive arterial disease. Stroke 2, 295-318 (1971). 27. Kannel, W. B. and Dawber, T. R. Hypertensive cardiovascular disease: The Framingham Study, in “Hypertension: Mechanisms and M-anagement.” (G. Onesti, K. E. Kim, and J. H. Moyer, Eds.), pp. 93- 1IO, Grune & Stratton, New York, 1973. 28. Kannel, W. B., Doyle, J. T., McNamara, P. M., Quickenton, P., and Gordon, T. Precursors of

CHD RISK FACTOR

29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42.

43. 44. 45.

STUDY IN ARGENTINA

461

sudden coronary death. Factors related to the incidence of sudden death. Circulation 51, 606-613 (1975). Kershbaum, A., Bellet, S., Caplan, R. F., and Feinberg, L. J. Effect of cigarette smoking on free fatty acids in patients with healed myocardial infarction. Amer. J. Curdiol. 10,204-208 (1962). Keys, A. Coronary heart disease in seven countries. Circulation 41(Suppl. I), 211 (1970). Kuller, L., Perper, J., and Cooper, M. Demographic characteristics and trends in arteriosclerotic heart disease mortality: Sudden death and myocardial infarction. Circulation 52(Suppl. III), 1-15 (1975). Levy, R. I., Fredrickson, D. S., Shulman, R., Bilheimer, D. W., Breslow, J. L., Stone, N. J., Lux, S. E., Sloan, H. R., Krauss, R. M., and Herbert, P. N. Dietary and drug treatment of primary hyperlipoproteinemia. Ann. Int. Med. 77, 267-293 (1972). Librach, G., Schadel, M., Seltzer, M., and Hart, A. Assessing incidence and risk factors in myocardial infarction. Geriatrics 30, 79-907 (1975). Lown, B., Calvert, A. F., Armington, R., and Michael, R. Monitoring for serious arrhythmias and high risk of sudden death. Circulation 52(Suppl. III), 189- 198 (1975). Margolis, J. R., Gillurn, R. F., Feinleib, M., Brasch, R., and Fabsitz, R. Comparisons with the Framingham heart study and previous short-term studies. Amer. J. Cardiol. 37, 61-67 (1976). Mason, J. K. Asymptomatic disease of coronary arteries in young men. Brir. Med. J. 2, 1234- 1237 (1963). Morris, J. N. Physical inactivity and coronary heart disease. Acra Cardiol. Suppl. 20, 95-103 (1974). Moss, A. J. Profile of high risk in people known to have coronary heart disease: A review. Circulation 52(Suppl. III), 147- 154 (1976). Neufeld, H. N. Precursores de la arterioesclerosis coronaria en grupos de edad pediatrica y de adultos jovenes. Conceptos Mod. Enferm. Cardiovasc. 43, 35-39 (1974). de Neuman, M. P. P., Martiarena, J. L., and Neuman, J. Betaglucuronidasa serica en la cardiopatia isquemica. Medicina 33, 123- 131 (1973). de Neuman, M. P. P., Martiarena, J. L., and Neuman, J. Prevalencia de hiperlipoproteinemias en la cardiopatia coronaria. Rev. Argent. Cardiol. 44, lCK- 115 (1976). Nichaman, M. Z., Hamilton, H. B., Kagan, A., Grier, T., Sacks, S. T., and Syme, S. L. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: Distribution of biochemical risk factors. Amer. J. Epidemiol. 102, 491-501 (1975). Noble, R. P. Electrophoretic separation of plasma lipoprotein in agarose gel. J. Lipid Res. 9, 693-700 (1968). Oglesby, P. Una encuesta en la epidemiologia de la hipertensi6n arterial 1964- 1974. Concepros Mod. Enferm. Cardiovasc. 43, 41-46 (1974). Oliver, M. F. Ischaemic heart disease in young women: A re-appraisal of the sex factor. Acta Cardiol.

Suppl.

20, 59-68

(1974).

46. Oscai, L. B., Patterson, J. A., Bogard, D. L., Beck, R. J., and Rothermel, B. L. Normalization of serum triglycerides and electrophoretic patterns by exercise. Amer. J. Cardiol. 30, 775-780 (1972). 47. Ostrander, L. D., and Lamphear, D. E. Coronary risk factors in a community. Findings in Tecumseh, Michigan. Circulation 53, 152- 156 (1976). 48. Paffenbarger, R. S., Notkin, J., Krueger, D. E., Wolf, P. A., Thorne, M. C., LeBauer, E. J., and Williams, J. L. Chronic disease in former college students. II. Methods of study and observations on mortality from coronary heart disease. Amer. J. Pub. Health 56, 962-971 (1966). 49. Palmero, H. A., and Caeiro, A. Epidemiologia de la hipertension arterial en Cordoba, Argentina. I. La presion arterial en funcion de la edad y el sexo. Medicina 31, 393-417 (1971). 50. Rappaport, F., and Eichhom, F. Sulfosalicylic acid as a substitute for paratoluene sulfonic acid. Clin. Chim. Acra 5, 161-163 (1960). 51. Reid, D. D., Hamilton, P. J. S., McCartney, P., and Rose, G. Smoking and other risk factors for coronary heart disease in British civil servants. Lancer 2, 979-983 (1976). 52. Report of Inter-Society Commission for Heart Disease Resources. Primary prevention of the atherosclerotic diseases. Circulation 42, 55-95 (1970).

462

NEUMAN

ET

AL.

53. Rhoads, G. G., Kagan, A., and Yano, K. Usefulness of community surveillance for the ascertainment of coronary heart disease and stroke. Int. J. Epidemiol. 4, 265-270 (1975). 54. Seely, S. Possible reasons for the comparatively high resistance of women to heart disease. Amer. Heart .I. 91, 275-280 (1976). 55. Stamler, J. Hypertension and coronary risk. Implications of current knowledge. Acta Cardiol. Suppl. 20, 119-157 (1974). 56. Stamler, J. Primary prevention of sudden coronary death. Circulation 52, 258-279 (1975). 57. Tomas Abadal, L., Balaguer Vintro, I., and Bernardes Bernat, E. Factores de riesgo e incidencia de nuevos cases en el estudio prospective de la cardiopatia isquemica de Manresa. Rev. &pan. Cur&o/. 29, 127- 135 (1976). 58. Veterans Administration Cooperative Study Group on Antihypertensive Agent. Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 213, 1143-1152 (1970). 59. Werko, L. Risk factors and coronary heart disease: Facts or fancy’? Amer. Heart J. 91, 87-98 (1976). ’ 60. Wilhelmsson, C., Vedin, J. A., Elmfeldt, D., Tibblin, G., and Wilhelmsen, L. Smoking and myocardial infarction. Lancet 1, 415-419 (1975). 61. Wissler, R. W., Vesselinovich, D., and Getz, G. S. Abnormalities of the arterial wall and its metabolism in atherogenesis. Progr. Cardiovasc. Dis. 18, 341-369 (1976). 62. Wissler, R. W., and Vesselinovich, D. Studies of regression of advanced atherosclerosis in experimental animals and man. Ann. N. Y. Acad. Sci. 275, 363-378 (1976). 63. Wood, P. D. S., Stern, M. P., Silvers, A., Reaven, G. M. Z., and Von Der Groeven, J. Prevalence of plasma lipoprotein abnormalities in a free-living population of the Central Valley, California. Circulation 45, 114- 126 (1972). 64. Zanchetti, A., and Malliani, A. Neural and psychological factors in coronary disease. Acta Cardbl. Suppl. 20, 69-93 (1974). 65. Zelis, R., Mason, D. T., Braunwald, E., et al. Effects of hyperlipoproteinemias and their treatment on the peripheral circulation. .I. C/in. Invest. 49, 1007-1015 (1970).