The Clinical Observation Of Low Diastolic Blood Pressure In Old Patients And Correlation Between ALDH2 Gene Polymorphisms And Blood Pressure

Objective and Backguangd:Hypertension is one of the most important cardiovascular disease risk factor, and is common diseases and frequently-occurring disease of older persons. Hypertension in the elderly has its own characteristics:systolic blood pressure increased mainly and apparent increase in diastolic blood pressure or it is not high, diastolic blood pressure is low in a large part of the elderly. The patients over age of 80 are special people, their blood pressure characteristics and antihypertensive therapy problems caused more and more concern. Low diastolic blood pressure will lead to organ insufficiency, seriously affecting the life quality and physical health of older persons, and it will cause confusion antihypertensive therapy. Nitrates can improve the pulse pressure increased in elderly hypertensive patients.The present study found that aldehyde dehydrogenase 2 (ALDH2) is a key enzyme of the biological metabolism of nitroglycerin in the body, the nitroglycerin (NTG) is metabolife of by ALDH2 and it can produce NDG and nitric oxide (NO), NO has vasodilative tunction.The polymorphism of ALDH2 gene result in reduced activities of some aldehyde dehydrogense(or no activity).Comparing systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) between ALDH2 genotypes to explore the relationship between the nitrates to improve the increased pulse pressure in elderly hypertensive patients.24-hour average diastolic blood pressure (24hmDBP) have certain advantages to reflect the phenomena of low diastolic blood pressure, we can take into account the duration of hypotension and daily activities on blood pressure. Retrospective the ambulatory blood pressure characteristics in elderly patients with hypertension and the correlation between low diastolic blood pressure and myocardial ischemia and cardiac function, and by comparing the ambulatory blood pressure parameters of different genotypes of ALDH2 patients with coronary heart disease (both routine taking nitroglycerin) to observe the effect of nitroglycerin. Subjects were divided into three parts:The first part:Ambulatory blood pressure characteristic of the very elderly patients with hypertensionMethods:Selected 193 hypertension patients in hospitalized the General Hospital of Beijing Military Region in November 2005 to July 2009.The patients were divided into three groups by age:age older group (n=88,≥80 years old), old age group (n=80,60～79 years), and middle-aged group (n=25,<60 years). Retrospective analyzed the ambulatory blood pressure parameters, the incidence of abnormal circadian blood pressure and the lowest diastolic< 60mmHg.Results:1.The situation of treatment:All patients were treated with lifestyle intervention therapy, including reasonable exercise, limiting sodium intake, potassium calcium, giving up smoking and limiting alcohol.89.6% patients receive regular antihypertensive treatment, in which monotherapy accounted for 27.5%, the two drugs combined accounted for 29%, taking 3 and more than 3 antihypertensive drugs are 64 cases, accounting for 33.1%.The difference was not statistically significant(χ2=12.85, P=0.23).2.The 24 hours ambulatory blood pressure parameters:The difference of 24hmSP,dmSBP and nmSBP of three groups were not significant.24hmDEP,dmDBP and nmDBP of age older group were lower than old age group and middle-aged group (P<0.01).24hmPP,dmPP and nmPP of age older group were higher than old age group and middle-aged group (P<0.01).3.24 hours circadian rhythm of blood pressure:The rate of abnormal BP day-night rhythm in age older group more than old age group and middle-aged group (χ2=15.53,P=0.017).4.Diastolic minimum value:The rate of the lowest diastolic pressure lower than 60mmHg in age older group were higher than old age group, the difference were both significant (P<0.01).5.Blood pressure overload rates:No significant difference in the daytime overload of systolic blood pressure and diastolic blood pressure among the three groups. Old age group, older group of night-time systolic and diastolic pressure overload was significantly lower than that of middle-aged group (P<0.01).Conclusion:In 24h ambulatory blood pressure monitoring of patients aged>80 years old with hypertension,more attention should be paid to low diastolic pressure and the abnormal BP day-night rhythm during BP lowering therapy.The second part:The clinical observation of low diastolic blood pressure in elderly hypertensive patients.Methods:Selected 168 elderly hypertension patients in hospitalized the General Hospital of Beijing Military Region in November 2005 to July 2009. Divided into three groups according to 24hmDBP:group A(n=43,24 hmDBP<60 mmHg), group B(n=71,24 hmDBP:60 mmHg-69 mmHg) and group C(n=54,24 hmDBP> 70 mmHg).Analysis the incidence of myocardial ischemia,the incidence of heart failure and cardiac function relevant indicators between three groups.Results:1. A general comparison of clinical features:The difference of average age was significant (χ2= 16.45,P<0.01),Sex, associated medical history, medication situation and the bilateral common carotid artery IMT values were no statistically significant difference among the three groups (P> 0.05).2.The incidence of coronary heart disease and heart failure and related indicators:By Logistic regression analyse, we found that age is a risk factor for coronary heart disease (OR:1.06,95% CI:1.01-1.11,P=0.012),24hmDBP with the incidence of coronary heart disease was significantly associated(OR:0.49,95%CI:0.29-0.86, P=0.01),the prevalence of coronary heart disease among the three groups were 86.0%,83.1%,and 55.6%; At the same time,24hmDBP also occur with myocardial ischemia rate (OR:0.58,95%CI:0.37-0.92, P=0.02) and the prevalence of heart failure (OR:0.62,95%CI:0.39-0.99, P= 0.04),the correlate was significantly. The lower 24hmDBP,the higter incidence of coronary heart disease, myocardial ischemia incidence and cardiac dysfunction. LVEF values between the three groups with no significant difference. The E/A value (H=7.29, P=0.03) and BNP(H=6.60, P=0.04) among the three groups, the difference were statistically.Conclusion:In elderly patients with hypertension treatment condition, the incidence of coronary heart disease,myocardial ischemia,and heart failure increased with the decrease of 24hmDBP. Low diastolic blood pressure on cardiac function may be mainly realized for the diastolic dysfunction.Antihypertensive therapy should be considered in coronary perfusion.The third part:Correlation between ALDH2 gene polymorphisms and hypertentionMethods:Selected 57 coronary heart disease patients in hospitalized the General Hospital of Beijing Military Region in November 2008 to November 2009.Using Pyrosequencing Analysis of ALDH2 gene G487A polymorphism,divide patients into two groups according to genotype: ALDH2 gene GG genotype group (n=43) and AA/AG genotype group (n=14), all patients who regularly take long-nitrates drugs and nitroglycerin. Comparison the incidence of hypertension, cardiovascular disease risk factors and systolic blood pressure, diastolic blood pressure, pulse pressure during treatment between the two groups in order to evaluate the correlation between the aldehyde dehydrogenase 2 gene polymorphism and blood pressure and to explore the nitrates in improving the low diastolic blood pressure in the elderly patients with coronary heart disease.Results:1.Results of ALDH2 genotype:According Pyromark ID pyrophosphate based sequencing results, ALDH2 genotype have three kinds:AA-type, GG-type and AG-type (Figure 2,3,4). AA-type is detected 3 cases (5.2%), GA-type has 11 cases(19.3%),and GG-type has 43 cases (75.5%).2.The general information of ALDH2 gene GG-type group and the AA/AG genotype group: the gender composition ratio, age, smoking, drinking, diabetes, FPG, CRP, TC, TG, LDL-c, HDL-c, BMI as well as the medication were no statistically significant differences between two groups (P> 0.05).3.The blood pressure characteristics of ALDH2 gene GG-type group and the AA/AG genotype group:The hypertension incidence of AA/AG genotype group (85.7%) was significantly higher than GG-type group (53.5%), the difference was statistically significant (χ2=4.63, P= 0.03).The difference of systolic and diastolic blood pressure between the two groups were not statistically significant,while the pulse pressure of AA/AG group (64.86±15.80mmHg) was significantly higher than GG group (49.84±12.92mmHg), the difference was statistically significant (Z=2.87,P<0.01). Conclusion:The G487A variant of aldehyde dehydrogenase-2(ALDH2) gene polymorphisms may be risk factor for hypertension, one of the mechanism may be related to the endogenous NO generation. In addition, its effect on the nitroglycerin may increase the pulse pressure in old patients with coronary heart disease.