Treatment drop-in in a contemporary cohort used to derive cardiovascular risk prediction equations.

BACKGROUND: No routinely recommended cardiovascular disease (CVD) risk prediction equations have adjusted for CVD preventive medications initiated during follow-up (treatment drop-in) in their derivation cohorts. This will lead to underestimation of risk when equations are applied in clinical practice if treatment drop-in is common. We aimed to quantify the treatment drop-in in a large contemporary national cohort to determine whether equations are likely to require adjustment. METHODS: Eight de-identified individual-level national health administrative datasets in Aotearoa New Zealand were linked to establish a cohort of almost all New Zealanders without CVD and aged 30-74 years in 2006. Individuals dispensing blood-pressure-lowering and/or lipid-lowering medications between 1 July 2006 and 31 December 2006 (baseline dispensing), and in each 6-month period during 12 years' follow-up to 31 December 2018 (follow-up dispensing), were identified. Person-years of treatment drop-in were determined. RESULTS: A total of 1 399 348 (80%) out of the 1 746 695 individuals in the cohort were not dispensed CVD medications at baseline. Blood-pressure-lowering and/or lipid-lowering treatment drop-in accounted for 14% of follow-up time in the group untreated at baseline and increased significantly with increasing predicted baseline 5-year CVD risk (12%, 31%, 34% and 37% in <5%, 5-9%, 10-14% and ≥15% risk groups, respectively) and with increasing age (8% in 30-44 year-olds to 30% in 60-74 year-olds). CONCLUSIONS: CVD preventive treatment drop-in accounted for approximately one-third of follow-up time among participants typically eligible for preventive treatment (≥5% 5-year predicted risk). Equations derived from cohorts with long-term follow-up that do not adjust for treatment drop-in effect will underestimate CVD risk in higher risk individuals and lead to undertreatment. Future CVD risk prediction studies need to address this potential flaw.

Paired risk scores to predict ischaemic and bleeding risk twenty-eight days to one year after an acute coronary syndrome.

OBJECTIVE: The recommended duration of dual anti-platelet therapy (DAPT) following acute coronary syndrome (ACS) varies from 1 month to 1 year depending on the balance of risks of ischaemia and major bleeding. We designed paired ischaemic and major bleeding risk scores to inform this decision. METHODS: New Zealand (NZ) patients with ACS investigated with coronary angiography are recorded in the All NZ ACS Quality Improvement registry and linked to national health datasets. Patients were aged 18-84 years (2012-2020), event free at 28 days postdischarge and without atrial fibrillation. Two 28-day to 1-year postdischarge multivariable risk prediction scores were developed: (1) cardiovascular mortality/rehospitalisation with myocardial infarction or ischaemic stroke (ischaemic score) and (2) bleeding mortality/rehospitalisation with bleeding (bleeding score). FINDINGS: In 27 755 patients, there were 1200 (4.3%) ischaemic and 548 (2.0%) major bleeding events. Both scores were well calibrated with moderate discrimination performance (Harrell's c-statistic 0.75 (95% CI, 0.74 to 0.77) and 0.69 (95% CI, 0.67 to 0 .71), respectively). Applying these scores to the 2020 European Society of Cardiology ACS antithrombotic treatment algorithm, the 31% of the cohort at elevated (>2%) bleeding and ischaemic risk would be considered for an abbreviated DAPT duration. For those at low bleeding risk, but elevated ischaemic risk (37% of the cohort), prolonged DAPT may be appropriate, and for those with low bleeding and ischaemic risk (29% of the cohort) short duration DAPT may be justified. CONCLUSION: We present a pair of ischaemic and bleeding risk scores specifically to assist clinicians and their patients in deciding on DAPT duration beyond the first month post-ACS.

Developing Non-Laboratory Cardiovascular Risk Assessment Charts and Validating Laboratory and Non-Laboratory-Based Models.

Background: Developing simplified risk assessment model based on non-laboratory risk factors that could determine cardiovascular risk as accurately as laboratory-based one can be valuable, particularly in developing countries where there are limited resources. Objective: To develop a simplified non-laboratory cardiovascular disease risk assessment chart based on previously reported laboratory-based chart and evaluate internal and external validation, and recalibration of both risk models to assess the performance of risk scoring tools in other population. Methods: A 10-year non-laboratory-based risk prediction chart was developed for fatal and non-fatal CVD using Cox Proportional Hazard regression. Data from the Isfahan Cohort Study (ICS), a population-based study among 6504 adults aged ≥ 35 years, followed-up for at least ten years was used for the non-laboratory-based model derivation. Participants were followed up until the occurrence of CVD events. Tehran Lipid and Glucose Study (TLGS) data was used to evaluate the external validity of both non-laboratory and laboratory risk assessment models in other populations rather than one used in the model derivation. Results: The discrimination and calibration analysis of the non-laboratory model showed the following values of Harrell's C: 0.73 (95% CI 0.71-0.74), and Nam-D'Agostino χ2:11.01 (p = 0.27), respectively. The non-laboratory model was in agreement and classified high risk and low risk patients as accurately as the laboratory one. Both non-laboratory and laboratory risk prediction models showed good discrimination in the external validation, with Harrell's C of 0.77 (95% CI 0.75-0.78) and 0.78 (95% CI 0.76-0.79), respectively. Conclusions: Our simplified risk assessment model based on non-laboratory risk factors could determine cardiovascular risk as accurately as laboratory-based one. This approach can provide simple risk assessment tool where laboratory testing is unavailable, inconvenient, and costly.

Nationwide trends in acute coronary syndrome by subtype in New Zealand 2006-2016.

OBJECTIVES: Recent studies in acute coronary syndrome (ACS) have reported mixed results for trends in ACS subtypes. The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) 31 study evaluated trends in ACS event rates, invasive management and mortality of ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina (UA) in New Zealand. METHODS: All ACS hospitalisations between 2006 and 2016 were identified from routinely collected national data and categorised into STEMI, NSTEMI, UA and MI unspecified (MIU). Annual hospitalisation, coronary procedure, 28-day and 1-year mortality rates were calculated and trends tested using Poisson regression adjusting for age and sex. RESULTS: Over the 11-year study period, there were 188 264 ACS admissions, of which 16.0% were STEMI, 54.5% NSTEMI, 25.7% UA and 3.8% MIU. Event rates of all ACS subtypes fell: STEMI by 3.4%/year, NSTEMI by 5.9%/year and UA by 8.5%/year, while the proportion of patients with ACS receiving angiography and revascularisation increased by 5.6% per year. Rates of percutaneous coronary intervention rose for STEMI, NSTEMI and UA, but coronary artery bypass grafting increased only for NSTEMI and UA. Mortality at 28 days and 1 year was higher for STEMI than NSTEMI and lowest for UA. There was a relative 1.6%/year decline in 1 year mortality for NSTEMI (p<0.001), but no significant change for STEMI and UA. CONCLUSIONS: We observed declines in the event rates of all ACS subtypes and increases in revascularisation rates. The finding that mortality declined in patients with NSTEMI, but not in patients with STEMI and UA, despite increases in invasive procedures, requires further investigation.

Trends in cardiovascular outcomes after acute coronary syndrome in New Zealand 2006-2016.

OBJECTIVES: Characterisation of trends in acute coronary syndrome (ACS) outcomes are critical to informing clinical practice and quality improvement, but there are few recent population studies for ACS. We reviewed the recent trends in the outcomes of ACS in New Zealand (NZ). METHODS: All patients with ACS admitted to NZ public hospitals in 2006-2016 were identified from hospital discharge records, and their first ACS hospitalisations per year extracted for analysis. Thirty-day and 1-year death, myocardial infarction, stroke, heart failure and bleeding rates were calculated for each calendar year. Trends in outcome rates were assessed using generalised linear mixed models. RESULTS: Total annual ACS hospitalisations decreased from 685 to 424 per 100 000. Using first patient hospitalisations per year (n=1 55 060), we found significant annual declines in all major outcomes except for non-cardiovascular deaths. All-cause mortality fell from 10.5% to 9.1% at 30 days (adjusted OR 0.985 per year change, p<0.001) and from 21.8% to 18.7% at 1 year (OR=0.994, p=0.016). This was related to significant decreases in cardiovascular death at both time points (OR=0.982 and 0.987, respectively, p<0.001), outweighing a slight increase in non-cardiovascular death at 1 year (OR=1.009, p=0.014). One-year rates of myocardial infarction, heart failure, stroke and bleeding rates all decreased significantly over time. CONCLUSION: ACS outcomes including all-cause mortality, cardiovascular death, myocardial infarction, stroke, heart failure and bleeding at 30 days and 1 year improved over the last decade in NZ, reflecting successful implementation and advances in prevention, medical and invasive management in ACS over time.

Performance of a Framingham cardiovascular risk model among Indians and Europeans in New Zealand and the role of body mass index and social deprivation.

Objectives: To evaluate a Framingham 5-year cardiovascular disease (CVD) risk score in Indians and Europeans in New Zealand, and determine whether body mass index (BMI) and socioeconomic deprivation were independent predictors of CVD risk. Methods: We included Indians and Europeans, aged 30-74 years without prior CVD undergoing risk assessment in New Zealand primary care during 2002-2015 (n=256 446). Risk profiles included standard Framingham predictors (age, sex, systolic blood pressure, total cholesterol/high-density lipoprotein ratio, smoking and diabetes) and were linked with national CVD hospitalisations and mortality datasets. Discrimination was measured by the area under the receiver operating characteristics curve (AUC) and calibration examined graphically. We used Cox regression to study the impact of BMI and deprivation on the risk of CVD with and without adjustment for the Framingham score. Results: During follow-up, 8105 and 1156 CVD events occurred in Europeans and Indians, respectively. Higher AUCs of 0.76 were found in Indian men (95% CI 0.74 to 0.78) and women (95% CI 0.73 to 0.78) compared with 0.74 (95% CI 0.73 to 0.74) in European men and 0.72 (95% CI 0.71 to 0.73) in European women. Framingham was best calibrated in Indian men, and overestimated risk in Indian women and in Europeans. BMI and deprivation were positively associated with CVD, also after adjustment for the Framingham risk score, although the BMI association was attenuated. Conclusions: The Framingham risk model performed reasonably well in Indian men, but overestimated risk in Indian women and in Europeans. BMI and socioeconomic deprivation could be useful predictors in addition to a Framingham score.

Serum lipid levels for a multicultural population in Auckland, New Zealand: results from the Diabetes Heart and Health Survey (DHAH) 2002-2003.

AIMS: To describe mean serum lipid concentrations for Maori, Pacific people (mostly of Samoan, Tongan, Niuean, or Cook Islands origin), and Others (mostly New Zealand-born Europeans), and to identify risk factors for an adverse lipid profile. METHODS: A cross-sectional survey of adults aged between 35-74 years within the Auckland area. There were 1006 Maori, 996 Pacific people, and 2021 'Others' Fasting blood samples were collected from participants, and total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and triglycerides were measured. RESULTS: Maori and Pacific people had similar mean serum total and LDL cholesterol levels but lower HDL levels and higher total to HDL cholesterol ratios compared to Others (adjusted for age and gender). Maori also had higher triglycerides than Others. High BMI and cigarette smoking were positively associated with unfavourable lipid profiles, while current alcohol drinking and vigorous leisure time activity were associated with increased HDL cholesterol and lower total to HDL cholesterol ratios. Over 90% of all ethnic groups had total cholesterol levels above currently accepted optimal levels (>4 mmol/L) and two-thirds were above 5 mmol/L. While 30% of Others had a total to HDL cholesterol ratio above the 'optimal' threshold of 4.5, 40% of Maori and 44% of pacific people were above this level. CONCLUSIONS: This is the first study to simultaneously assess lipid levels in Maori, Pacific people, and Others in one population-based study. Despite similar total and LDL cholesterol levels in all ethnic groups; overweight, obesity, and current cigarette smoking were the main risk factors for their adverse lipid profiles. Engaging in leisure-time activity and alcohol consumption (and not surprisingly lipid-lowering drugs) were associated with better lipid profiles. We confirm that the main lipid-related cardiovascular disease risk in Maori and Pacific people is due to their low HDL and high triglyceride levels.