Background  The baseline characteristics of patients in a multinational trial are possibly related to cardiovascular outcome. This study compared the baseline characteristics of patients recruited in China with those recruited in other countries.
Methods  A total of 508 Chinese hypertensive men and 728 women over the age of 80 years who entered the Hypertension in the Very Elderly Trial (HYVET) were compared with those in 860 men and 1348 women who entered the trial in other countries.
Results  The Chinese subjects were slightly younger, had less previous hypertension but more previous strokes than the subjects from other countries. The Chinese subjects smoked more than those from other countries, but drank less alcohol. They had less previous episodes of myocardial infarction and were, on average, lighter and shorter. The Chinese had lower mean concentrations of blood urea, uric acid and creatinine as well as higher concentrations of high density lipoprotein (HDL) cholesterol. The concentration of total cholesterol was, on average, lower in the Chinese subjects as was blood glucose. The levels of serum sodium and potassium, blood hematocrit and hemoglobin were all, on average, lower in the Chinese subjects.
Conclusions  Calorie restriction, compared with the rest of the world, may have resulted in lower stature and weight, and recent increases in calorie intake have not changed the metabolic profile of the very elderly hypertensive patients in China. Some of these biochemical differences may reflect different dietary lifestyle in the Chinese.

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The Hypertension in the Very Elderly Trial (HYVET) is being performed to determine the risks and benefits of treating the very elderly (aged 80 years and over) hypertensive patients with a low-dose diuretic indapamide 1.5 mg slow release (SR), to which perindopril 2–4 mg may be added aiming at reaching goal blood pressure (150/80 mmHg) or below. The trial is conducted double blind versus placebo around the world.¹ The entry criteria include an average systolic blood pressure (after 1–2 months of taking placebo tablets) of 160 to 199 mmHg and a diastolic pressure <110 mmHg. The trial aims to include an ethnic mix of patients so that the results are generalized. The active countries include China; Bulgaria, Romania and Russia in Eastern Europe; Finland, France and the United Kingdom in Western Europe; and Tunisia and New Zealand. Thus the HYVET recruits a mixed population but has few Black Africans or Asians from the Indian subcontinent. Nevertheless, the results will be representative of several populations although the diverse nature of these different populations has to be examined.

The characteristics of the very elderly in China are of particular interest owing to the high stroke and low cardiac mortality observed in this country,² and the fact that the prevalence of the metabolic syndrome is increasing rapidly in China.^3,4 Moreover, China is a very large country and the prevalence of constituents of the metabolic syndrome varies considerably from North to South, and from urban to rural areas. The prevalence is lower in the South and in the rural areas,⁵ because of a lower socio-economic status.^6,7 This article compares the baseline characteristics of patients recruited in China with those recruited in the other countries.

The subjects who thought to be eligible for the HYVET (aged 80 years or over, hypertensive, no serious co-morbidity likely to impair survival) were given an information sheet in the local language, and written informed consent was obtained. Ethical committee agreement was obtained at local and national levels as required. The trial protocol has been published¹ as have the main sub-study protocols.^8-10 After obtaining the consent, the investigator asked the subject to stop all antihypertensive medications and to take the trial treatment (1 placebo tablet daily). After one month the subject returned to have sitting blood pressure measured and this constituted the first reading contributing to the entry blood pressure. After one more month the patient again attended and a second entry sitting blood pressure was measured together with the standing pressure. Each blood pressure measurement was performed twice. If the average of the two readings on 2 occasions (4 measurements) was 160 to 199 mmHg for sitting systolic pressure and <110 mmHg for sitting diastolic pressure and all other inclusion criteria were met, the subject may be randomised into the trial. Three visits were designated randomisation month minus 2 (M-2), randomisation month minus 1 (M-1) and at randomisation (M-0), respectively, the latter being the last reading. Anthropometric measures, blood tests and all other baseline information were collected between visits M-2 and M-0 and reported at M-0. The data presented in this article consist of known and suspected cardiovascular risk factors reported at M-0. These data are required for a full understanding of the outcome of the trial and also indicate any regional differences in risk factors in the HYVET.

The baseline results for China were compared with those for the other areas of the world. There were 508 Chinese men and 728 Chinese women who were compared with 860 men and 1348 women from other countries. The information considered is listed in Tables 1 and 2 and was available in over 98% of men and women with the exception of urea (96% and 95% of other men and women, respectively) and high density lipoprotein (HDL) cholesterol (87% and 90% of men and women from other countries, respectively). The non-available results included a minimal number of grossly out-lying results. A total of 59.0% of the Chinese subjects were women and 61.1% of the subjects from other countries (P=0.22).

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Table 1. Characteristics of subjects at entry to the HYVET in China and other countries

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Table 2. Baseline measurements on subjects entered in the HYVET in China and other countries

Because of the slightly different proportions of women in the 2 groups, the qualitative data were analyzed using log likelihood method to simultaneously determine a Z score and significance for both regional and gender differences and regional x gender interaction terms. The quantitative data were analyzed using a multiple regression model including region, gender and interaction terms. P <0.05 was considered statistically significant.

Tables 1 and 2 show the regional results for men and women separately. The gender differences in alcohol consumption, smoking habits, previous myocardial infarction and stroke, body weight, body height, cholesterol, urea, creatinine, uric acid, hemoglobin and hematocrit are too well recognized to deserve further comment. The gender difference in total cholesterol was 0.2–0.3 mmol/L and higher in women.

The regional differences consisted of a slightly lower average age in the Chinese (0.1–1.0 year), and more smokers and fewer drinkers of alcohol in China. The Chinese had previously experienced fewer episodes of myocardial infarction and congestive heart failure and more strokes. They were lighter and shorter and had lower average body mass indices. The biochemical components of metabolic syndrome (except systolic blood pressure which was standardized by trial entry criteria) were all favourable in the Chinese. Total cholesterol was 11% lower, HDL cholesterol 8% higher, and glucose 2% lower in the Chinese. Fasting blood was taken in 97% of the Chinese and 86% of the subjects in other countries. Average fasting blood glucose was 5.29 mmol/L in the Chinese and 5.48 mmol/L in the subjects in other countries. Fasting blood glucose was therefore 3% lower in the Chinese subjects. The trial protocol was altered during the trial to allow the entry of subjects with normal levels of diastolic pressure (subjects with isolated systolic hypertension, ISH). These patients were recruited later in the trial than those in other countries, showing a higher proportion of subjects with ISH and therefore lower average diastolic pressures. Systolic pressures were similar at entry in women in China to the average observed in other countries. This was also true for the standing systolic in men but the sitting systolic pressure was lowered by 2 mmHg on average in Chinese men than men in other countries and the pulse rate was increased by 1 beat/minute.

Measures of renal function were better in the Chinese. Urea was lowered by 9%, creatinine by 8%, and uric acid by 5%. Average serum potassium was lowered by over 3% in the Chinese and serum sodium by 1.4%. Average hemoglobin was lowered by 1% and hematocrit by 2% in the Chinese.

Although the prevalence of the metabolic syndrome is reported to be increasing in China as the population becomes more affluent,^3,4 blood cholesterol and glucose were found to be lower in the very elderly Chinese population than the subjects in other countries. These countries were mainly in Eastern Europe including Bulgaria (n=1597), Romania (n=254) and the Russian Federation (n=198). The subjects in these countries have less favourable biochemical results than the Chinese in this study. This conclusion assumes that the laboratory methods are indeed equivalent in the different countries and that we studied equivalent proportions of urban and rural subjects. As far as we can determine we recruited in both rural and urban areas in both Europe and China. The differences between the HYVET patients recruited in the different European countries have been discussed previously.^11,12 The Chinese may prove to be particularly prone to develop the metabolic syndrome in comparison with Europeans.¹³ But the elderly Chinese recruited to the HYVET do not have this problem and they had a deficit of previous diagnoses of myocardial infarction and congestive heart failure.

The Chinese subjects, however, did report a higher prevalence of previous stroke, agreeing with the fact that more strokes are observed in the Chinese compared with European populations.^2,14 Sodium consumption is high in China, especially in the North, and the excess of strokes can be explained to some extent by higher body mass index, higher sodium intake and reduced potassium intake.⁵ Nevertheless, serum sodium was not increased in the Chinese subjects (in fact the reverse) but serum potassium was lower. This supports that the high Na⁺/K⁺ ratio in the diet in China may be less favourable.¹⁵ Certainly the Chinese diet is lower in dietary fat and sugars and higher in total carbohydrate and starch.¹⁶ The lower body mass index in our very elderly Chinese subjects presumably reflects lower calorie consumption and the relatively low haemoglobin and hematocrit fits into this pattern. The prevalence of anemia has been reported to be high in China and related to the risk of diabetes in women.¹⁷ The Chinese subjects drank less alcohol but were more likely to smoke. There is evidence, however, that smoking is associated with a more adverse metabolic profile and peripheral vascular disease in China.¹⁸ It is interesting that the blood pressure raising effects of alcohol may be more important in some Chinese populations than in others.¹⁹ The same may be true for the association between raised body mass index and raised blood pressure.¹⁹ The genetic differences between different populations in China may affect the concentration of serum cholesterol²⁰ and the level of serum uric acid²¹ and urban/rural differences in smoking and alcohol consumption are marked.²²

The finding that renal function is better preserved in Chinese subjects had been discussed previously. These studies considered the appropriate adjustments for body mass index and age^23-25 and the fact that renal function in Chinese is related to three candidate genes.²⁶

From the point of view of the HYVET, there is little reason to expect that the comparisons of actively and placebo treated patients will be affected by the baseline differences between the Chinese and the other elderly populations. Nevertheless, if active treatment is proportionally more beneficial to stroke reduction rather than reducing cardiac events, then, theoretically, active treatment may be more successful in China than in Europe. This possibility and the reverse situation of greater benefit in Europe will be explored in the final analyses of the trial.

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