Yue Qi

Dietary factors associated with hypertension

Hypertension is one of the major risk factors for cardiovascular disease, with an impact on global health. Multiple studies have suggested that various dietary factors are associated with blood pressure (BP) and hypertension. The purpose of this Review is to provide up-to-date knowledge on the impact of dietary factors on BP and hypertension, to compare types and recommended intakes of dietary factors in hypertension management and prevention guidelines from different countries and organizations, and to outline global population-based healthy-diet strategies for hypertension control. Of the 27 dietary factors we evaluated on the basis of specified review criteria, 17 have been proposed to have protective effects against hypertension, six were proposed to be risk factors for hypertension, and the association between BP and the remaining factors was considered inconclusive. Excessive sodium intake is a causal risk factor for hypertension, whereas a diet rich in fruit, vegetables, and low-fat dairy products, and low in sodium and saturated fat has been recommended to prevent and reduce hypertension on the basis of strong evidence. Notable differences exist in the recommended types and intakes of dietary factors among available hypertension management and prevention guidelines. Available evidence supports the vigorous implementation of dietary strategies against hypertension through population-based, national action plans.

The relationship between apolipoprotein E ε2/ε3/ε4 polymorphisms and hypertension: a meta-analysis of six studies comprising 1812 cases and 1762 controls

We performed a meta-analysis in an effort to systematically explore the association between apolipoprotein E (ApoE) ɛ2/ɛ3/ɛ4 polymorphisms and hypertension. We searched for case–control studies in English-language publications performed with human subjects using MEDLINE and included appropriate studies that had been published as of 6 May 2009. Fixed-effects models were used to pool data when between-study heterogeneity was absent, and random-effects models were used otherwise. Data and study quality were assessed in duplicate. Publication bias was assessed by calculating the fail-safe number. From six heterogeneous studies that included a total of 1812 patients with hypertension and 1762 controls, we found that the ApoE ɛ4 allele was significantly associated with hypertension using a random-effects model (odds ratio (OR)=1.79; 95% confidence interval (CI): 1.04 to 1.19; P=0.04). With regard to ApoE genotypes, we observed that the association with hypertension was more prominent when ApoE4/4 was compared with E3/3, with a nearly twofold increased risk identified for the ApoE4/4 genotype using a random-effects model (OR=1.97; 95% CI: 1.11 to 3.52; P=0.02). Furthermore, after restricting our analysis to Asian populations, the contrasts between the risk of hypertension among individuals possessing ApoE ɛ4 vs. ɛ3 and ApoE4/4 vs. ApoE3/3 were positively reinforced, with ORs of 1.97 (95% CI, 0.93 to 4.15; P=0.08) and 2.27 (95% CI, 1.03 to 4.98; P=0.04), respectively. The fail-safe number supported these significant associations at a significance level of 0.05. Taken together, our meta-analysis expands the data available regarding genetic risk factors for hypertension by illustrating that the presence of the ApoE ɛ4 allele is associated with an increased risk of developing hypertension and that it appears to be recessive. Of note, this effect was more pronounced in Asians.

Association of interleukin-6 circulating levels with coronary artery disease: A meta-analysis implementing mendelian randomization approach ☆

BACKGROUND We aim to investigate whether the association between circulating interleukin 6 (IL-6) levels and the risk for coronary artery disease (CAD) is robust and perhaps even causal by a meta-analysis implementing mendelian randomization approach with IL-6 gene G-174C polymorphism as an instrument. METHODS Data were available from 19 articles encompassing 9417 CAD patients and 15982 controls. A random effects model was applied irrespectively of between-study heterogeneity, and publication bias was examined using a funnel plot and the corresponding statistics. RESULTS Overall, comparison of IL-6 gene alleles -174C with -174G had 4% increased risk for CAD (95% confidence interval [95% CI]: 0.97-1.10; P=0.285), accompanying marginal heterogeneity (I(2)=38.3%; P=0.033). This association was potentiated in dominant model as odds ratio (OR) reached 1.08 (95% CI: 0.96-1.22; P=0.204) and heterogeneity was significant (I(2)=58.4%; P<0.0005). Subgroup analysis by ethnicity indicated that carriers of -174C allele were associated with a 12% increased risk for CAD in prospective studies involving White populations (OR=1.12; 95% CI: 0.95-1.33; P=0.184), whereas the association in East Asians was remarkably reversed with 37-46% reduced risk. Relative to -174GG homozygotes, carriers of -174C allele had an overall 0.24 pg/ml high circulating IL-6 levels (P=0.047). The predicted OR for 1 pg/ml elevation in IL-6 levels was 1.60 (95% CI: 1.44-1.72; P<0.01) in prospective studies involving White populations. Publication biases were absent for all comparisons (P>0.1). CONCLUSION Our findings provided strong evidence on the causal association of circulating IL-6 levels with the development of CAD in White populations.

Cholesterol-Overloaded HDL Particles Are Independently Associated With Progression of Carotid Atherosclerosis in a Cardiovascular Disease-Free Population: A Community-Based Cohort Study

BACKGROUND Cholesterol-overloaded high-density lipoprotein (HDL) particles exert a negative impact on the antiatherogenic function of HDL in experimental studies. However, it remains unclear whether cholesterol-overloaded HDL particle is involved in the development of atherosclerosis in humans. OBJECTIVES The objective of this study was to explore whether cholesterol-overloaded HDL particles are associated with the progression of carotid atherosclerosis in a cardiovascular disease-free population. METHODS Baseline HDL particle number was measured using nuclear magnetic resonance spectroscopy in 930 participants ages 45 to 74 years in a community-based cohort study. An estimate of cholesterol molecules per HDL particle (HDL-C/P ratio) was calculated as the ratio of HDL cholesterol to HDL particles. HDL-C/P ratio was categorized as <41.0 (lowest), 41.0 to 46.9, 47.0 to 52.9, and ≥53.0 (highest) using a fixed increment method. Modified Poisson regression was used to assess the association between HDL-C/P ratio and 5-year progression of carotid atherosclerosis as indicated by progression of carotid plaques and change in total plaque area (TPA). RESULTS Mean baseline HDL-C/P ratio was 46.4 ± 9.3 (range 23.8 to 86.9). Baseline HDL-C/P ratio was significantly associated with 5-year progression of carotid atherosclerosis. Participants with the highest HDL-C/P ratio had 1.56-fold (95% confidence interval: 1.14 to 2.13; p = 0.006) increased progression compared with those with the lowest level. Among participants without baseline plaque, TPA in re-examination was larger by 9.4 mm(2) in the subgroup with the highest level when compared with the lowest level. CONCLUSIONS Our findings suggest that cholesterol-overloaded HDL particles are independently associated with the progression of carotid atherosclerosis. This may explain why in recent trials raising HDL cholesterol was not beneficial. This study strongly suggests that the combination of cholesterol content and particle number determines the antiatherogenic function of HDLs, rather than either parameter alone.

An updated meta-analysis of methylenetetrahydrofolate reductase gene 677C/T polymorphism with diabetic nephropathy and diabetic retinopathy

Studies investigating the association of methylenetetrahydrofolate reductase (MTHFR) gene 677C/T polymorphism with diabetic nephropathy and diabetic retinopathy have so far reported inconclusive results. We therefore aim to address this inconclusiveness by conducting a meta-analysis. Random-effects model was applied irrespective of between-study heterogeneity. Data and study quality were assessed in duplicate. A total of 7807 and 1599 subjects from 21 and 8 studies were analyzed for diabetic nephropathy and diabetic retinopathy, respectively. Carriers of 677TT genotype were 1.71 (95% confidence interval [95% CI]: 1.02-2.88; P=0.042) and 2.89 (95% CI: 1.51-5.53; P=0.001) times more likely to develop diabetic nephropathy separately relative to diabetic patients without nephropathy and nondiabetic controls. Likewise, this association was preserved for diabetic patients with retinopathy referring to those without (odds ratio [OR]=1.86; 95% CI: 1.21-2.86; P=0.004). Subgroup analyses showed that ethnicity was a possible confounder, especially in West Asians and Africans, and so were gender and duration of diabetes mellitus in diabetic nephropathy studies. Probability of publication bias was low across all comparisons as reflected by the funnel plot and corresponding test. Taken together, our results demonstrate that MTHFR gene 677TT genotype might confer a moderately augmented risk for diabetic nephropathy and diabetic retinopathy.

Cardiovascular risk assessment: a global perspective

An important strategy in primary prevention of cardiovascular diseases (CVD) is the early identification of high-risk individuals. Effective implementation of a strategy to identify these individuals in a clinical setting is reliant on the availability of appropriate CVD risk-assessment models and guideline recommendations. Several well-known models for CVD risk assessment have been developed and utilized in the USA and Europe, but might not be suitable for use in other regions or countries. Very few reports have discussed the development of risk-assessment models and recommendations from a global perspective. In this Review, we discuss why risk-assessment methods developed from studies in one geographical region or ethnic population might not be suitable for other regions or populations, and examine the availability and characteristics of predictive models in areas beyond the USA or Europe. In addition, we compare the differences in risk-assessment recommendations outlined in CVD clinical guidelines from developed and developing countries, and consider their potential effect on clinical practice. This overview of cardiovascular risk assessment from a global perspective can potentially guide low-to-middle-income countries in the development or validation of their own CVD risk-assessment models, and the formulation of recommendations in their own clinical guidelines according to local requirements.

A meta-analysis of receptor for advanced glycation end products gene: four well-evaluated polymorphisms with diabetes mellitus.

Genetic association studies on the gene encoding receptor for advanced glycation end products (RAGE) and diabetes mellitus have reported conflicting results. To evaluate the association of RAGE gene four widely-evaluated polymorphisms (T-429C, T-374A, Gly82Ser and G1704T) and diabetes mellitus, a meta-analysis was conducted. A random-effects model was applied irrespective of between-study heterogeneity. There were a total of 5808/3742 (n=14) case-patients/controls (studies) for T-429C, 8259/6935 (n=19) for T-374A, 7029/5266 (n=19) for Gly82Ser, and 2843/3302 (n=13) for G1704T. Overall results detected no significant association of polymorphisms T-429C, T-374A and Gly82Ser with diabetes risk. There was a trend toward an increased risk for alleles 1704T relative to 1704G (odds ratio [OR]=1.09; 95% confidence interval [CI]: 0.98-1.22; I(2)=0). Subgroup analysis by ethnicity indicated that allele 1704T conferred a significantly increased risk in East Asians (OR=1.21; 95% CI: 1.04-1.4; I(2)=0) but not in Caucasians (OR=0.8; 95% CI: 0.6-1.07; I(2)=0), and that by type of diabetes mellitus indicated that association was potentiated exclusively for G1704T with diabetic retinopathy (OR=1.24; 95% CI: 1.01-1.51; I(2)=0). No publication bias was observed. Our results provide convincing evidence regarding the association of RAGE gene 1704T allele with an increased risk of diabetes mellitus, especially diabetic retinopathy. Notably, this effect was more pronounced in East Asians.

Association between plasma PCSK9 levels and 10-year progression of carotid atherosclerosis beyond LDL-C: A cohort study

BACKGROUND To evaluate the association of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels with the progression of carotid atherosclerosis and identify additional PCSK9-lipoprotein-atherosclerosis pathway beyond low-density lipoprotein cholesterol (LDL-C). METHODS Among 643 participants (aged from 45 to 74years) free of cardiovascular disease at baseline, carotid ultrasound examinations were performed in 2002 (baseline) and 2012 (follow-up). None of the participants were taking lipid-lowering drugs or had detectable carotid plaques at baseline. Carotid plaque formation and total plaque area (TPA) were used to reflect 10-year progression of atherosclerosis. RESULTS Baseline plasma PCSK9 levels have a wide variation, ranged from 64.60-532.20ng/mL (median: 192.57ng/mL). PCSK9 levels were significantly associated with new plaque formation after adjusting for LDL-C levels and other risk factors (relative risk for per quartile increase=1.09, 95% confidence interval: 1.03-1.15). PCSK9 levels were also linearly associated with TPA after multivariate adjustment including LDL-C (P=0.008). Among participants with the lowest or second tertile of LDL-C, PCSK9 quartiles were linearly associated with TPA (P=0.021), but the association lost significance after additional adjustment for very low-density lipoprotein cholesterol (VLDL-C) tertiles (P=0.072). Further stepwise linear regression (entry, 0.05; removal, 0.05) indicated that VLDL-C tertiles could be entered into the model but PCSK9 quartiles could not. CONCLUSIONS Plasma PCSK9 levels are associated with 10-year progression of atherosclerosis. The LDL-independent association of PCSK9 levels may through its ability to regulate VLDL-C levels. Further research is needed to systematically investigate the role of PCSK9 for the pathogenesis of atherosclerosis, beyond LDL-C metabolism.

Review: Association between angiotensin converting enzyme G2350A polymorphism and hypertension risk: a meta-analysis

Background and objective: An exonic polymorphism G2350A (rs4343) in angiotensin converting enzyme (protein: ACE; gene: ACE) was shown to exert the most significant influence on plasma ACE levels. We therefore performed a meta-analysis to investigate association of ACE G2350A polymorphism with hypertension. Methods: Published case-control studies in English were identified. A total of four studies with 1699 cases and 1274 controls were identified. A random-effects model was performed irrespective of the between-study heterogeneity. Study quality was assessed in duplicate. Results: Compared with 2350G, the ACE 2350A allele conferred a protective effect on hypertension (odds ratio (OR) = 0.81; 95% confidence interval (CI), 0.56-1.18; p = .28). Similarly, comparisons of 2350AA and 2350GA with 2350GG generated a nonsignificant reduced risk, respectively. Under the dominant model, the ACE 2350A allele conferred a reduced hypertension risk and such associations were divergent between Han Chinese and Muslims from the Arab Gulf and Pakistan. Under the recessive model, this protective effect was totally reversed (OR = 1.01; 95% CI, 0.77-1.33; p = .94). Subgroup analyses indicated a significant protective effect of ACE 2350A compared with 2350G among Muslims from the Arab Gulf and Pakistan (OR = 0.55; 95% CI, 0.42-0.71; p < .00001). No publication biases were observed. Conclusions: Our results demonstrate that the ACE 2350A allele is associated with a significantly reduced hypertension risk among Muslims from the Arab Gulf and Pakistan, yet an elevated risk among Han Chinese.BACKGROUND AND OBJECTIVE An exonic polymorphism G2350A (rs4343) in angiotensin converting enzyme (protein: ACE; gene: ACE) was shown to exert the most significant influence on plasma ACE levels. We therefore performed a meta-analysis to investigate association of ACE G2350A polymorphism with hypertension. METHODS Published case-control studies in English were identified. A total of four studies with 1699 cases and 1274 controls were identified. A random-effects model was performed irrespective of the between-study heterogeneity. Study quality was assessed in duplicate. RESULTS Compared with 2350G, the ACE 2350A allele conferred a protective effect on hypertension (odds ratio (OR) = 0.81; 95% confidence interval (CI), 0.56-1.18; p = .28). Similarly, comparisons of 2350AA and 2350GA with 2350GG generated a nonsignificant reduced risk, respectively. Under the dominant model, the ACE 2350A allele conferred a reduced hypertension risk and such associations were divergent between Han Chinese and Muslims from the Arab Gulf and Pakistan. Under the recessive model, this protective effect was totally reversed (OR = 1.01; 95% CI, 0.77-1.33; p = .94). Subgroup analyses indicated a significant protective effect of ACE 2350A compared with 2350G among Muslims from the Arab Gulf and Pakistan (OR = 0.55; 95% CI, 0.42-0.71; p < .00001). No publication biases were observed. CONCLUSIONS Our results demonstrate that the ACE 2350A allele is associated with a significantly reduced hypertension risk among Muslims from the Arab Gulf and Pakistan, yet an elevated risk among Han Chinese.

Impact of Mineralocorticoid Receptor Antagonists on Changes in Cardiac Structure and Function of Left Ventricular Dysfunction

Background—A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists on cardiac remodeling is lacking. We aimed to evaluate the impact of mineralocorticoid receptor antagonists on changes in cardiac structure and function of left ventricular dysfunction. Methods and Results—Articles were identified by online searches in PubMed, EMBASE, Cochrane, and ClinicalTrials.gov databases before June 2012, by hand searches of reviews and relevant journals, and by contact with the authors. Qualified articles were restricted to randomized controlled trials. There were, respectively, 12, 4, and 3 qualified trials that randomized 572, 647, and 407 patients to spironolactone, canrenoate, and eplerenone, and 531, 655, and 395 patients to placebo or active treatment, respectively. Overall, under mineralocorticoid receptor antagonist treatment there was improvement in left ventricular ejection fraction (weighted mean difference, 2.97; 95% confidence interval [95% CI], 2.26–3.67; P<0.0005), left ventricular end-systolic and end-diastolic volume index (weighted mean difference, −5.64; 95% CI, −7.94 to −3.34; P<0.0005 and weighted mean difference, −7.46; 95% CI, −11.63 to −3.3; P<0.0005), serum amino-terminal peptide of procollagen type-III (weighted mean difference, −1.12; 95% CI, −1.49 to −0.74; P<0.0005), B-type natriuretic peptide (weighted mean difference, −67.06; 95% CI, −91.24 to −42.88; P<0.0005), peak velocities of early mitral inflow (E; weighted mean difference, −9.57; 95% CI, −12.98 to −6.17; P<0.0005), and E wave deceleration time (weighted mean difference, 7.08; 95% CI, 4.07–10.09; P<0.0005). There was low probability of heterogeneity and publication bias. Conclusions—Our findings demonstrate that mineralocorticoid receptor antagonist treatment may exert beneficial effects on the reversal of cardiac remodeling and improvement of left ventricular function.