| Hypertension is one of the most common chronic diseases, as well as the most important risk factor of cardiovascular disease (CVD). The major complications of hypertension, such as coronary heart disease (CHD), heart failure, stroke and chronic kidney disease (CKD), cause a heavy burden for families and society. With the social and economic development, the incidence of hypertension increases year by year, and has become an important public health problem of the21st century in China.Many clinical studies have demonstrated that hypertension is a chronic disease which can be prevented and controlled. Prevention and treatment of high blood pressure can significantly reduce the burden of CVD and CKD. However, the rates of awareness, treatment and control for hypertension patients remain low in China. Therefore, we must emphasize the importance of primary prevention of hypertension. In2003, the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) proposed a new blood pressure (BP) category of120-139mmHg systolic blood pressure (SBP) or80-89mmHg diastolic blood pressure (DBP) and designated it as "prehypertension". The incidence of prehypertension is up to30-50%. Prehypertensive individuals are prone to progress into frank hypertension, and most of them, are with clustering of other cardiovascular risk factors. However, the term of "prehypertension" has been contentious. Most arguments against using this term include that it could cause the public anxiety and overtreatment, there is heterogeneity within this category because the risk of progressing to hypertension and developing CVD is higher in people with BP130-139/85-89mmHg range than in those with BP120-129/80-84mmHg, and it remains unclear whether mild BP elevation directly increases the risk of CVD or whether other concurrent risk factors are responsible for the increase.Given these inconsistent results, we conducted a retrospective analysis to explore the prevalence of prehypertension, and the cardiovascular risk factors in the sub-groups of prehypertension. Furthermore, we performed a series of meta-analyses of prospective cohort studies to evaluate the association between prehypertension and all cause and cardiovascular mortality, CVD, CHD, stroke and end-stage renal disease (ESRD) incidence. This study is comprised of six parts:Chapter I Prevalence and Risk Factors Associated with Prehypertension in Shunde District, Southern ChinaIn China, the incidence of hypertension is significantly higher in the northern than that in the southern area. Such regional factors may also affect the incidence of prehypertension. However, the incidence of prehypertension in Guangdong province was rarely reported. Furthermore, whether the concurrent cardiovascular risk factors in subgroups of prehypertension are different remains unanswered. In this chapter, we performed a retrospective study in Shunde Destrict, Guangdong Province, using the community-based health check-up information, to explore the incidence and combined cardiovascular risk factors of prehypertension. Methods Community-based health check-up information was collected in the Health Management Center of the First People’s Hospital of Shunde. Individuals were divided into hypertension (SBP≥140mmHg and/or DBP≥90mmHg, or previous diagnosed as hypertension and now taking anti-hypertensive medicines); prehypertension (SBP120-139mmHg and/or DBP80-89mmHg) and optimal BP (SBP<120mm Hg and DBP<80mmHg). Prevalence and risk factors of prehypertension were analyzed. Prehypertension was further divided into low range (SBP120-129and/or DBP80-84mmHg) and high range (SBP130-139mmHg and/or DBP85-89mmHg) subgroups. The cardiovascular risk factors in the subgroups were compared. Results1.5,362cases (aged>35years) were initially reviewed and651of them were excluded due to missing data. Finally,4711cases (male2674, female2037) were analyzed. The proportion of optimal BP, prehypertension and hypertension were39.1%(1842cases),38.6%(1819cases) and22.3%(1050cases) respectively. The incidence of prehypertension was higher in male than in female (43.5%vs.32.2%, P<0.001).2. The average age, proportion of male, overweight, impaired fasting glucose (IFG), dyslipidemia, hyperuricemia, levels of fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), body mass index (BMI) and serum uric acid (UA) were significantly higher in prehypertension group than that in optimal BP group (all P<0.05).3. The proportion of male, overweight and IFG, levels of BMI and FPG were higher in low range prehypertension than that in optimal BP group (all P<0.05), but there were no significant differences in other cardiovascular risk factors (all P>0.05). The proportion of male, overweight, obesity, dyslipidemia, diabetes, IFG and hyperuricemia, levels of BMI, TC, low density lipoprotein-cholesterol, TG, FPG and UA were higher in high range prehypertension than that in optimal BP group (all P<0.05). Compared with low range prehypertension, the proportion of overweight, dyslipidemia and IFG were higher in the high range prehypertension (all P<0.05).4. Multivariate logistic regression analysis showed that overweight [odds ratio (OR)=2.89,95%confidence interval (CI)=1.56-5.35, P<0.001], male (OR=2.15,95%CI=1.37-3.37, P<0.001) and hyperuricemia (OR=1.69,95%CI=1.18-2.64, P=0.02) were independent risk factors for prehypertension. Conclusions Prehypertension is highly prevalent in Shunde Destrict, Guangdong Province. Prehypertensive individuals were companied with other cardiovascular risk factors, such as overweight, dyslipidemia, impaired glucose and uric acid metabolism. There was heterogeneity of combined risk factors within the prehypertensive subgroups.Chapter II Meta Analysis of Prehypertension and the Risk of All-Cause and Cardiovascular MortalityWe had documented in chapter I that prehypertension was highly prevalent and companied with multiple cardiovascular risk factors. There was heterogeneity of combined risk factors within the prehypertensive subgroups. However, studies of prehypertension and mortality are controversial after adjusting for other cardiovascular risk factors. This meta analysis sought to evaluate the association of prehypertension with all-cause and cardiovascular mortality. Methods The PubMed, EMBASE, and Cochrane Library databases, and conference proceedings were searched for studies with data on prehypertension and mortality. The relative risks (RRs) of all-cause, cardiovascular, CHD, and stroke mortality were calculated and reported with95%CIs. Subgroup analyses were conducted according to BP ranges, age, gender, ethnicity, follow-up duration, participant number, and study characteristics. Results1. Data from1,129,098participants were derived from20prospective cohort studies. Prehypertension significantly increased the risk of cardiovascular, CHD, and stroke mortality (RR=1.28,95%CI=1.16-1.40, P<0.001; RR=1.12,95%CI=1.02-1.23, P=0.02and RR=1.41,95%CI=1.28-1.56, P<0.001respectively), but did not increase the risk of all-cause mortality after multivariate-adjustment (RR=1.03,95%CI=0.97-1.10, P=0.35). The difference between the CHD mortality and the stroke mortality was significant (P<0.001). Subgroup analyses showed that high range prehypertension significantly increased the risk of cardiovascular mortality (RR=1.28,95%CI=1.16-1.41, P<0.0001) but low range prehypertension did not increase the risk (RR=1.08,95%CI=0.98-1.18, P=0.12). Conclusions Prehypertension is associated with cardiovascular mortality, especially with stroke mortality, but not with all-cause mortality. The risk cardiovascular mortality is largely driven by high range prehypertension.Chapter III Meta Analysis of Prehypertension and Incidence of Cardiovascular DiseaseIn chapter I, we found that individuals with prehypertension, even those in low range group, was associated with increased BMI and impaired glucose metabolism. However, we found that the increased cardiovascular mortality associated with prehypertension was largely driven by high range, but not low range group in chapter Ⅱ. It should be noted that cardiovascular mortality is not equal to CVD incidence. Prospective cohort studies of prehypertension and the incidence of CVD are controversial after adjusting for other cardiovascular risk factors. This meta analysis aimed to evaluate the association between prehypertension and composite CVD morbidity. Methods Two independent reviewers searched the same databases described in chapter II for prospective cohort studies with data on prehypertension and CVD morbidity. The RRs of CVD, CHD, and stroke morbidity were calculated and reported with95%CIs. Subgroup analyses were conducted according to BP ranges, age, gender, ethnicity, follow-up duration, number of participants, and study quality. Results Pooled data included the results from499,308participants from20prospective cohort studies. Prehypertension elevated the risks of CVD (RR=1.58,95%CI=1.43-1.73, P<0.001); CHD (RR=1.50,95%CI=1.30-1.74, P<0.001); and stroke (RR=1.74;95%CI=1.60-1.89, P<0.001). The difference between the CHD and stroke incidence was not significant (P=0.09). In the subgroup analyses, even for low range prehypertension, the risk of CVD was significantly higher than for optimal BP (RR=1.47,95%CI=1.34-1.61, P<0.001), and further increased with high range prehypertension (RR=1.85,95%CI=1.62-2.12, P<0.001). The relative risk was significantly higher in the high range prehypertensive populations than in the low range populations (P=0.005). There were no significant differences among other subgroup analyses (all P>0.05). Conclusions Prehypertension, even in the low range, elevates the risk of CVD after adjusting for multiple cardiovascular risk factors.Chapter IV Meta Analysis of Prehypertension and the Risk of StrokeWe had found that the incidence of CVD was increased from the low range prhypertension in chapter III. Among cardiovascular events, stroke shows the strongest association with BP. We also documented that the risk of stroke mortality was higher than CHD mortality in prehypertensive individuals in chapter II. However, the risks of stroke in different BP ranges of prehypertension have not been explored. This meta analysis sought to evaluate the risk of stroke (including stroke mortality and morbidity) associated with prehypertension, as well as its different subgroups. Methods We searched the same databases described in chapter II for prospective cohort studies with data on prehypertension and stroke. Two independent reviewers assessed the reports and extracted data. Prospective studies were included if they reported multivariate-adjusted RRs with95%CIs for the associations between stroke and prehypertension, or its two sub-ranges (low range prehypertension:120-129/80-84mmHg; high range prehypertension:130-139/85-89mmHg). We conducted subgroup analyses according to BP ranges, stroke type, endpoint, age, sex, ethnicity, and study characteristics. Results Pooled data included the results with762,393participants from19prospective cohort studies. Prehypertension increased the risk of stroke (RR=1.66,95%CI=1.51-1.81, P<0.001) compared with optimal BP (<120/80mmHg). In the subgroup analyses, even low range prehypertension increased the risk of stroke (RR=1.44,95%CI=1.27-1.63, P<0.001), and the risk was greater for high range prehypertension (RR=1.95,95%CI=1.73-2.21, P<0.001). The relative risk was higher with high range than with low range prehypertension (P<0.001). There were no significant differences among all subgroup analyses (all P>0.05). Conclusions After adjusting for multiple cardiovascular risk factors, prehypertension is associated with increased risk of stroke. The results were consistent across stroke type, stroke endpoint, age, study characteristics, follow-up duration, and ethnicity. Although the risk is largely driven by high range prehypertension, it is also increased in people with low range prehypertension.Chapter V Meta Analysis of Prehypertension and the Risk of Coronary Heart DiseaseWe had reported that prehypertension was associated with composite CVD and stroke risk. However, the effects of abnormal BP on coronary and cerebral arteries are not identical. Coronary perfusion is closely related to BP (especially DBP), so low BP levels may lead to increased risk of CHD (J-curve phenomenon). However, the findings are not consistent. In the prior chapters, we had reported that prehypertension was associated with CHD incidence and mortality respectively. However, the risks of CHD in different BP range of prehypertension have not been explored. Furthermore, the risks of CHD is significant different in different ethnicities. However, whether prehypertension affects the risk of CHD in Asians and Westerners differently remains unclear. This meta analysis sought to evaluate the risk of CHD (including CHD mortality and morbidity) associated with prehypertension, as well as its different subgroups. Methods We searched the same databases described in chapter II for prospective cohort studies with data on prehypertension and CHD. Two independent reviewers assessed the reports and extracted data. Prospective studies were included if they reported multivariate-adjusted RRs with95%CIs for the associations between CHD and prehypertension, or its two sub-ranges. We conducted subgroup analyses according to BP ranges, CHD endpoint, age, sex, ethnicity, and study characteristics. Results Pooled data included the results with561,664participants from17prospective cohort studies. Prehypertension increased the risk of CHD (RR=1.43,95%CI=1.26-1.63, P<0.001) compared with optimal BP (<120/80mmHg). In the subgroup analyses, even low range prehypertension increased the risk of CHD (RR=1.27,95%C/=1.07-1.50, P=0.007), and the risk trended to increase for high range prehypertension (RR=1.58,95%CI=1.24-2.02, P<0.001). The difference between low range and high range prehypertension was not significant (P=0.15). The risk of CHD was higher in Westerners than in Asians (Westerners:RR=1.71,95%CI=1.54-1.89, P<0.001; Asians:RR=1.23,95%CI=1.13-1.33, P<0.001; subgroup comparison:P<0.001). Conclusions After adjusting for multiple cardiovascular risk factors, prehypertension is associated with increased risk of CHD, especially in Westerners. The risk is also increased in people with low range prehypertension.Chapter VI Meta Analysis of Prehypertension and the Risk of End-stage Renal DiseaseIn the prior chapters, we had reported that prehypertension was associated with increased risks of CVD, CHD and stroke. However, studies of prehypertension and renal damage are controversial. Data from cross-section studies showed that prehypertension, particularly high-range prehypertension, is associated with CKD and ESRD. However, it is difficult to establish the detrimental effect of prehypertension on the kidneys from cross-section studies, as kidney disease itself can elevate BP. Prospective studies evaluated the association of prehypertension and ESRD are controversial after adjusting for other cardiovascular risk factors. This meta analysis aimed to evaluate the association of prehypertension with the incidence of ESRD. Methods The same databases described in chapter Ⅱ were searched for studies with data on prehypertension and ESRD. The RRs of ESRD morbidity were calculated and reported with95%CIs. Subgroup analyses were conducted according to BP ranges, age, gender, ethnicity, and study characteristics. Results Data from1,003,793participants were derived from6prospective cohort studies. Prehypertension significantly increased the risk of ESRD (RR=1.59,95%CI=1.39-1.91, P<0.001). In the subgroup analyses, prehypertension significantly predicted higher ESRD risk across subgroups with analyses conducted according to BP ranges, participant’s age, gender, ethnicity, and study characteristics. Even low range prehypertension increased the risk of ESRD compared with optimal BP (RR=1.44,95%CI=1.19-1.74, P<0.001), and the risk further increased with high range prehypertension (RR=2.02,95%CI=1.70-2.40, P<0.001). The relative risk was significantly higher in the high range than in the low range prehypertensive populations (P=0.01). Conclusions Prehypertension is associated with ESRD morbidity. The increased risk is largely driven by high range prehypertension.SummaryPrehypertension is a common worldwide health problem. The prevalence of prehypertension is more than30%, and most of the individuals are companied with multiple cardiovascular risk factors. Furthermore, the combined risk factors are more significant in people with high range prehypertension. After adjusting for multiple cardiovascular risk factors, prehypertension is associated with increased risks of cardiocascular and renal mortality and morbidity. These findings reaffirmed the importance of the definition of prehypertension, as well as the inhomogeneity of the prehypertension subcategories. Healthcare professionals should recommend lifestyle changes to subjects after prehypertension is discovered. High-risk subpopulations with prehypertension, especially high range prehypertension, are needed to be selected for future controlled trials of pharmacological treatment. |
