Angela S. Koh

The association between dietary omega-3 fatty acids and cardiovascular death: the Singapore Chinese Health Study.

Background Although studies suggest that omega-3 fatty acids intake may reduce cardiovascular disease (CVD) mortality risk, few studies have differentiated dietary eicosapentaenoic/docosahexaenoic acid (EPA/DHA) from alpha-linolenic acid (ALA), and epidemiological research in Asian populations is limited. Methods The Singapore Chinese Health Study is a population-based cohort that recruited 63,257 Chinese adults aged 45–74 years from 1993 to 1998. Usual diet was measured at recruitment using a validated semiquantitative food-frequency questionnaire, and mortality information was identified via registry linkage up to 31 December 2011. Cox proportional hazard models were used to calculate hazard ratios (HRs) with adjustment for potential confounders. Results We documented 4780 cardiovascular deaths (including 2697 coronary heart disease (CHD) deaths and 1298 stroke deaths) during 890,473 person-years of follow up. Omega-3 fatty acids intake was monotonically associated with reduced risk of cardiovascular mortality. Compared to the lowest quartile, the HR was 0.88 (95% confidence interval, CI, 0.81–0.96), 0.88 (95% CI 0.80–0.97), and 0.83 (95% CI 0.74–0.92) for the second, third, and highest quartile, respectively (p-trend = 0.003). Both EPA/DHA and ALA were independently associated with reduced risk of cardiovascular mortality: HR comparing extreme quartiles was 0.86 (95% CI 0.77–0.96, p-trend = 0.002) and 0.81 (95% CI 0.73–0.90, p-trend < 0.001), respectively. The associations were similar for deaths from CHD and stroke and persisted in participants who were free of CVD at baseline. Conclusions Higher intakes of marine (EPA/DHA) and plant (ALA) omega-3 fatty acids are both associated with reduced risk of cardiovascular mortality in a Chinese population.

Long-term outcomes after coronary bare-metal-stent and drug-eluting-stent implantations: a 'real-world' comparison among patients with diabetes with diffuse small vessel coronary artery disease.

Background and aimDrug-eluting stents (DESs) have been reported to be more efficacious compared with bare-metal stents (BMSs) in reducing the need for target vessel revascularization (TVR). However, the long-term benefits for patients with diabetes with small vessel disease are less certain. We aim to determine the clinical outcome of patients with diabetes with diffuse small vessel coronary artery disease who undergo percutaneous coronary intervention. MethodsThis is a single-center prospective registry of all patients with diabetes with target lesions implanted with stents that were 2.25 mm or less in diameter and approximately 20 mm in total stent length between January 2002 and October 2008. Primary outcome was combined major adverse cardiovascular events: death, nonfatal myocardial infarction and TVR up to 5 years. Outcomes were adjusted for age, sex and cardiovascular risk factors. ResultsThere were 544 patients (63% males, mean age 62±10 years) with 1010 lesions that were followed up for a mean duration of 3±2 years. Two hundred and thirty-nine patients (439 lesions) received BMS whereas 305 (571 lesions) received DES. DES lesions were longer (mean length 23.3±6.96 vs. 17.8±5.02 mm, P<0.001) than BMS lesions. Procedural success was similar for BMS and DES patients (86.2 vs. 86.6%, P=0.90). DES patients had less TVR at 6 months [3.9 vs. 9.2%, odds ratio (OR): 4.90, 95% confidence interval (CI): 1.53–15.65, P=0.007], 1 year (1 vs. 3.8%, OR: 8.01, 95% CI: 1.25–51.10, P=0.028) and3 years (13.8 vs. 18.0%, OR: 5.50, 95% CI: 3.74–8.13, P=0.043). By 5 years, the primary outcome was lower in DES patients (21.6 vs. 28%, OR: 1.79, 95% CI: 1.14–2.80, P=0.011). Independent predictors of TVR at 6 months were above or equal to 59 years of age (OR: 0.95, 95% CI: 0.90–1.00, P=0.032) and use of glycoprotein-IIbIIIa inhibitors (OR: 0.02, 95% CI: 0.001–0.50, P=0.018). Stent length was not a significant predictor of TVR. ConclusionOur observational analysis suggests that DES seems to have short-term and mid-term advantages over BMS in reducing TVR and overall major adverse cardiovascular events. Percutaneous coronary intervention with DES may be considered as an option in these patients with limited revascularization options.

Percutaneous coronary intervention in asians- are there differences in clinical outcome?

BackgroundEthnic differences in clinical outcome after percutaneous coronary intervention (PCI) have been reported. Data within different Asian subpopulations is scarce. We aim to explore the differences in clinical profile and outcome between Chinese, Malay and Indian Asian patients who undergo PCI for coronary artery disease (CAD).MethodsA prospective registry of consecutive patients undergoing PCI from January 2002 to December 2007 at a tertiary care center was analyzed. Primary endpoint was major adverse cardiovascular events (MACE) of myocardial infarction (MI), repeat revascularization and all-cause death at six months.Results7889 patients underwent PCI; 7544 (96%) patients completed follow-up and were included in the analysis (79% males with mean age of 59 years ± 11). There were 5130 (68%) Chinese, 1056 (14%) Malays and 1001 (13.3%) Indian patients. The remaining 357 (4.7%) patients from other minority ethnic groups were excluded from the analysis. The primary end-point occurred in 684 (9.1%) patients at six months. Indians had the highest rates of six month MACE compared to Chinese and Malays (Indians 12% vs. Chinese 8.2% vs. Malays 10.7%; OR 1.55 95%CI 1.24-1.93, p < 0.001). This was contributed by increased rates of MI (Indians 1.9% vs. Chinese 0.9% vs. Malays 1.3%; OR 4.49 95%CI 1.91-10.56 p = 0.001), repeat revascularization (Indians 6.5% vs. Chinese 4.1% vs. Malays 5.1%; OR 1.64 95%CI 1.22-2.21 p = 0.0012) and death (Indians 11.4% vs. Chinese 7.6% vs. Malays 9.9%; OR 1.65 95%CI 1.23-2.20 p = 0.001) amongst Indian patients.ConclusionThese data indicate that ethnic variations in clinical outcome exist following PCI. In particular, Indian patients have higher six month event rates compared to Chinese and Malays. Future studies are warranted to elucidate the underlying mechanisms behind these variations.

Systolic blood pressure and cardiovascular mortality in middle-aged and elderly adults - The Singapore Chinese Health Study.

BACKGROUND While elevated systolic blood pressure (SBP) is related to cardiovascular disease (CVD) mortality, it is unclear if the optimal SBP level may differ by age or the presence of underlying CVD. OBJECTIVE We investigated the association between SBP categories and CVD mortality among middle-aged and elderly adults with and without CVD history. METHODS We used data from 30,692 participants of the population-based Singapore Chinese Health Study who had blood pressures measured using a standard protocol at ages 48-85years between 1994 and 2005. Information on lifestyle factors were collected at recruitment (1993-1998) and during follow-up interviews (1999 and 2004). Mortality was identified via nationwide registry linkage up to 31 December 2014. RESULTS SBP 120-139mmHg category was associated with lowest risk of CVD mortality in both age-groups of <60 and 60+years, as well as in those with and without underlying coronary heart disease or stroke. Overall, compared to this category, CVD risk was non-significantly increased in lower SBP categories and significantly increased in the higher SBP categories. The risk estimates associated with elevated SBP were higher among those <60years compared to their older counterparts, but less distinct between those with and without underlying CVD. CONCLUSION SBP 120-139mmHg was associated with the lowest risk of CVD mortality in middle aged and elderly adults, regardless of underlying CVD. Although risks in both adult groups were similar, there is a greater risk associated with higher SBP among those aged below 60years, highlighting a greater urgency of treatment in this younger group.

Dissecting Clinical and Metabolomics Associations of Left Atrial Phasic Function by Cardiac Magnetic Resonance Feature Tracking

Among community cohorts, associations between clinical and metabolite factors and complex left atrial (LA) phasic function assessed by cardiac magnetic resonance (CMR) feature tracking (FT) are unknown. Longitudinal LA strain comprising reservoir strain (εs), conduit strain (εe) and booster strain (εa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using CMR FT. Targeted mass spectrometry measured 83 circulating metabolites in serum. Sparse Principal Component Analysis was used for data reduction. Among community adults (n = 128, 41% female) (mean age: 70.5 ± 11.6 years), age was significantly associated with εs (β = −0.30, p < 0.0001), εe (β = −0.3, p < 0.0001), SRs (β = −0.02, p < 0.0001), SRe (β = 0.04, p < 0.0001) and SRe/SRa (β = −0.01, p = 0.012). In contrast, heart rate was significantly associated with εa (β = 0.1, p = 0.001) and SRa (β = −0.02, p < 0.0001). Serine was significantly associated with εs (β = 10.1, p = 0.015), SRs (β = 0.5, p = 0.033) and SRa (β = −0.9, p = 0.016). Citrulline was associated with εs (β = −4.0, p = 0.016), εa (β = −3.4, p = 0.002) and SRa (β = 0.4, p = 0.019). Valine was associated with ratio of SRe:SRa (β = −0.4, p = 0.039). Medium and long chain dicarboxyl carnitines were associated with εs (β = −0.6, p = 0.038). Phases of LA function were differentially associated with clinical and metabolite factors. Metabolite signals may be used to advance mechanistic understanding of LA disease in future studies.

Comparing the use of cobalt chromium stents to stainless steel stents in primary percutaneous coronary intervention for acute myocardial infarction: A prospective registry

Objectives: To determine clinical outcome and rates of target vessel revascularization (TVR) in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI who were treated with cobalt-chromium stents compared to stainless steel bare metal stents (BMS). Background: The newer generation cobalt chromium stents were reported to achieve lower rates of TVR compared with conventional BMS. Methods: Consecutive STEMI cases admitted within 12 h of symptom onset and undergoing primary angioplasty and bare metal stent implantation 1 January 2002 and 31 December 2008 were identified. Primary outcomes were rates of clinically-driven TVR at six months as well as occurrence of major adverse cardiovascular events (MACE) either of all-cause death, repeat myocardial infarction or TVR at six months. Results: 1030 cases with 1175 lesions (84% males) and median age of 58 years underwent primary PCI for STEMI in our registry. Overall procedural success rate was 98%. Stainless steel stents were inserted in 65% of the culprit lesions (stainless steel, n = 766 versus cobalt chromium, n = 264). Primary outcomes of TVR (3.5% in the stainless steel group and 3.4% in the cobalt chromium group, P = 0.93) and MACE (8.4% in the stainless steel group and 5.3% in the cobalt chromium group, P = 0.11) after six months were no different between the two groups. However, there were more deaths at 30 days in the stainless steel group compared to the cobalt chromium group (3.5% versus 0.4%, HR 4.04 (1.03–3.88), P = 0.04). Conclusion: Both cobalt-chromium and stainless steel coronary stents were associated with similar and low risk of clinically-driven TVR.

Association of “Elevated Blood Pressure” and “Stage 1 Hypertension” With Cardiovascular Mortality Among an Asian Population

Background The new American College of Cardiology/American Heart Association high blood pressure (BP) guidelines in the United States have lowered definition of hypertension by defining normal as systolic/diastolic BP <120/80 mm Hg; elevated BP as systolic between 120 and 129 mm Hg and diastolic <80 mm Hg; and stage 1 hypertension as systolic between 130 and 139 mm Hg or diastolic between 80 and 89 mm Hg. Methods and Results We investigated the association between the new hypertension definition and cardiovascular disease mortality among Chinese in Singapore. We used data from 30 636 participants of a population‐based cohort, the SCHS (Singapore Chinese Health Study), who had BPs measured using a standard protocol at ages 46 to 85 years between 1994 and 2005. Information on lifestyle factors was collected at recruitment (1993–1998) and follow‐up 1 interviews (1999 and 2004). Mortality was identified via nationwide registry linkage up to December 31, 2016. Neither elevated BP (hazard ratio, 0.89; 95% confidence interval, 0.74–1.07) nor stage 1 hypertension (hazard ratio, 0.94; 95% confidence interval, 0.81–1.11) was associated with increased risk of cardiovascular mortality compared with normal BP in the whole cohort. Stage 1 hypertension was associated with increased cardiovascular risk only in those <65 years of age and without a history of cardiovascular disease (hazard ratio, 1.40; 95% confidence interval, 1.01–1.94), but not in those ≥65 years of age or with a history of cardiovascular disease. Conclusions Our data suggest that the newly defined stage 1 hypertension may not be associated with increased cardiovascular mortality across all ages among Chinese in Singapore, but that the at‐risk subpopulation is limited to those <65 years of age and without a prior cardiovascular disease.

Normal Values of Myocardial Deformation Assessed by Cardiovascular Magnetic Resonance Feature Tracking in a Healthy Chinese Population: A Multicenter Study

Reference values on atrial and ventricular strain from cardiovascular magnetic resonance (CMR) are essential in identifying patients with impaired atrial and ventricular function. However, reference values have not been established for Chinese subjects. One hundred and fifty healthy volunteers (75 Males/75 Females; 18–82 years) were recruited. All underwent CMR scans with images acceptable for further strain analysis. Subjects were stratified by age: Group 1, 18–44 years; Group 2, 45–59 years; Group 3, ≥60 years. Feature tracking of CMR cine imaging was used to obtain left atrial global longitudinal (LA Ell) and circumferential strains (LA Ecc) and respective systolic strain rates, left ventricular longitudinal (LV Ell), circumferential (LV Ecc) and radial strains (LV Err) and their respective strain rates, and right ventricular longitudinal strain (RV Ell) and strain rate. LA Ell and LA Ecc were 32.8 ± 9.2% and 40.3 ± 13.4%, respectively, and RV Ell was −29.3 ± 6.0%. LV Ell, LV Ecc and LV Err were −22.4 ± 2.9%, −24.3 ± 3.1%, and 79.0 ± 19.4%, respectively. LV Ell and LV Ecc were higher in females than males (P < 0.05). LA Ell, LA Ecc, and LV Ecc decreased, while LV Err increased with age (P < 0.05). LV Ell and RV Ell were not shown to be associated with age. Normal ranges for atrial and ventricular strain and strain rates are provided using CMR feature tracking in Chinese subjects.

Metabolomic profile of arterial stiffness in aged adults

Background: Increasing arterial stiffness is an important contributor to declining cardiovascular health in ageing. Changes in whole-body fuel metabolism could be related to alterations in arterial stiffness in ageing adults. Methods: Targeted high-performance liquid and gas chromatography mass spectrometry were used to measure 84 circulating metabolites in a group of community elderly adults (n = 141, 58% men; mean age = 70.6 ± 11.2 years) without cardiovascular disease. In basic and adjusted models, we correlated the measured metabolites to carotid–femoral pulse wave velocity assessed by applanation tonometry. Results: Age (β = 0.10, p < 0.0001), smoking status (β = 1.32, p = 0.02), dyslipidemia (β = 1.22, p = 0.01), central systolic blood pressure (β = 0.05, p < 0.0001), central mean arterial pressure (β = 0.04, p = 0.03) and central pulse pressure (β = 0.05, p < 0.0001) were significantly associated with pulse wave velocity. Amino acids such as histidine, methionine and valine correlated with pulse wave velocity. In multivariable models adjusted for clinical covariates, only Factor 5, comprising the medium- and long-chain dicarboxyl and hydroxyl acylcarnitines was independently associated with pulse wave velocity (β = 0.24, p = 0.015). Conclusion: An upstream metabolic perturbation comprising medium- and long-chain dicarboxyl and hydroxyl acylcarnitines, likely reflecting changes in cellular fatty acid oxidation, was associated with arterial stiffness among aged adults. This advances mechanistic understanding of arterial stiffness among aged adults before clinical disease.

Quantification of Biventricular Strains in Heart Failure With Preserved Ejection Fraction Patient Using Hyperelastic Warping Method

Heart failure (HF) imposes a major global health care burden on society and suffering on the individual. About 50% of HF patients have preserved ejection fraction (HFpEF). More intricate and comprehensive measurement-focused imaging of multiple strain components may aid in the diagnosis and elucidation of this disease. Here, we describe the development of a semi-automated hyperelastic warping method for rapid comprehensive assessment of biventricular circumferential, longitudinal, and radial strains that is physiological meaningful and reproducible. We recruited and performed cardiac magnetic resonance (CMR) imaging on 30 subjects [10 HFpEF, 10 HF with reduced ejection fraction patients (HFrEF) and 10 healthy controls]. In each subject, a three-dimensional heart model including left ventricle (LV), right ventricle (RV), and septum was reconstructed from CMR images. The hyperelastic warping method was used to reference the segmented model with the target images and biventricular circumferential, longitudinal, and radial strain–time curves were obtained. The peak systolic strains are then measured and analyzed in this study. Intra- and inter-observer reproducibility of the biventricular peak systolic strains was excellent with all ICCs > 0.92. LV peak systolic circumferential, longitudinal, and radial strain, respectively, exhibited a progressive decrease in magnitude from healthy control→HFpEF→HFrEF: control (-15.5 ± 1.90, -15.6 ± 2.06, 41.4 ± 12.2%); HFpEF (-9.37 ± 3.23, -11.3 ± 1.76, 22.8 ± 13.1%); HFrEF (-4.75 ± 2.74, -7.55 ± 1.75, 10.8 ± 4.61%). A similar progressive decrease in magnitude was observed for RV peak systolic circumferential, longitudinal and radial strain: control (-9.91 ± 2.25, -14.5 ± 2.63, 26.8 ± 7.16%); HFpEF (-7.38 ± 3.17, -12.0 ± 2.45, 21.5 ± 10.0%); HFrEF (-5.92 ± 3.13, -8.63 ± 2.79, 15.2 ± 6.33%). Furthermore, septum peak systolic circumferential, longitudinal, and radial strain magnitude decreased gradually from healthy control to HFrEF: control (-7.11 ± 1.81, 16.3 ± 3.23, 18.5 ± 8.64%); HFpEF (-6.11 ± 3.98, -13.4 ± 3.02, 12.5 ± 6.38%); HFrEF (-1.42 ± 1.36, -8.99 ± 2.96, 3.35 ± 2.95%). The ROC analysis indicated LV peak systolic circumferential strain to be the most sensitive marker for differentiating HFpEF from healthy controls. Our results suggest that the hyperelastic warping method with the CMR-derived strains may reveal subtle impairment in HF biventricular mechanics, in particular despite a “normal” ventricular ejection fraction in HFpEF.