台灣心臟代謝性疾病之預防及治療—肥胖/過重、糖尿病、癌症及心血管疾病

Abstract

背景：關於心臟代謝性疾病之心血管疾病（Cardiovascular disease, CVD）的預防，先前缺乏肥胖/過重此危險因子對於台灣 CVD負擔相關的研究。而關於心臟代謝性疾病的治療，以升糖素胜肽-1受體的促效劑（Glucagon-Like Peptide-1 Receptor Agonist, GLP-1 RAs）降低體重和血糖，過去研究也未曾考慮統合分析（meta-analysis）中不同結果之間的相關性。再者，過去對於台灣特殊族群癌症病人的 CVD 預防，研究結果並不一致。 目的：量化可歸因於高身體質量指數（Body Mass Index, BMI）之 CVD 疾病負擔；探討 GLP-1 RAs 對血糖和體重控制的效果及其相關性；並探討台灣常見癌症病人，相較於非癌症族群之 CVD 風險。 方法：使用全球疾病負擔研究中的可比較性風險評估方法，依性別、年齡和縣市別估計台灣的族群歸因分率 （Population Attributable Fraction, PAF）、可歸因之 CVD 疾病負擔和失能調整生命人年損失 （Disability Adjusted Life Years, DALY）以量化疾病負擔。搜尋 2021 年 8 月至 2022 年 3 月的文獻資料庫，使用平均差值（Mean Difference, MD）和 95％ 信賴區間（Confidence Interval, CI）進行分析， 採用隨機和固定效應模型，並以結構方程式模型多變項統合分析，探討 GLP-1 RAs 對血糖和體重控制的效果量及其相關程度。最後，以台灣癌症登記檔，將常見癌症患者納入研究，研究終點是致命和非致命 CVD。使用 Cox 回歸分析估計多變項調整風險比（Hazard Ratios, HR）和 95％ CI，並估計診斷後每年的風險以評估時間趨勢變化。 結果：台灣疾病負擔中，高 BMI 導致 CVD 的可歸因 PAF 為 18.0 ％， 60－65 歲的成年人絕對 DALYs 損失最高為 11,546 人年，平均相對年齡標準化可歸因疾病負擔為每十萬人年 314 DALYs 損失，人年損失最多在年齡 75－80 歲（每十萬人年 1,407 DALYs 損失）。至於 GLP-1 RAs 對血糖和體重控制的效果及其相關，共納入 31篇雙盲隨機對照試驗， 22,948 名參與者。 GLP-1 RAs 經統合分析，可減少糖化血色素 MD 和 95% CI ，在隨機效應模型中為 -0.78（-0.97 , -0.60）％，在固定效應模型中為 -0.45（-0.47, -0.44) ％；經隨機效應模型統合，可減少體重 -4.05（-5.02, -3.09）kg，經固定效應模型統合為 -2.04（-2.16, -1.92）kg。 統合後糖化血色素與體重之間的標準化相關係數為負相關 -0.42。最後，在 552,485 名癌症患者（平均年齡 60.6 歲，女性 47.7％）中，經過 4.1 年追蹤，確認了 32,634 例 CVD 病例，相較於非癌族群，癌症患者整體經完全調整後之 HR 和 95％ CI 為 1.28（1.25－1.30）；第一年的 CVD 風險最高，調整後的 HR 和 95% CI 為 2.31（2.23－2.40），之後風險逐年降低。 結論：若能去除肥胖/過重，可以減少台灣 18 ％ 的 CVD，肥胖/過重的絕對 CVD 疾病負擔在中年男性最高，而相對負擔則在老年人最高，需針對特定地區及族群妥善資源分配。以長效 GLP-1 RAs 可顯著降低成人糖化血色素和體重，血糖控制和體重減輕之間為負相關。另外，癌症患者之 CVD 的風險顯著升高，該風險在診斷後的第一年最高，之後逐年下降。

Background: In the prevention of cardiometabolic disease, studies on risk factors, obesity/ overweight and disease burden in Taiwan were lacking. In the treatment of cardiometabolic disease, previous studies did not investigate the between-study correlation of glycemic control and weight reduction of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) in meta-analysis. Furthermore, the associations with cancer and CVD in Taiwan had inconsistent results. Aims: To quantify the CVD burden attributable to high body mass index (BMI) in Taiwan; to explore the effect and correlation of GLP-1 RAs on glycemic and weight reduction and to investigate the risk of CVD between populations with and without cancer. Methods: Using a comparative risk assessment approach from the Global Burden of Disease study, we estimated the population attributable fraction (PAF), attributable CVD burden, and disability-adjusted life years (DALYs) according to sex, age, and area in Taiwan to quantify CVD burden. Databases were searched from August 2021 to March 2022. Data were analyzed using mean difference (MD) values with 95% confidence intervals (CIs). Both random-and fixed-effect models were employed. Structural equation modeling fitting was used for the multivariate meta-analysis to explore the effect and correlation of GLP-1 RAs on glycemic and weight reduction. Finally, patients with common cancers were enrolled in the study using the Taiwan Cancer Registry. The study endpoint was fatal and non-fatal CVD. Multivariable adjusted hazard ratios (HRs) and 95% CIs were obtained from Cox analysis. To evaluate the chronological trend, we estimated the risks yearly since the diagnosis. Results: The attributable PAF for CVD from high BMI was 18.0%. Adults aged 60-65 years had the highest absolute DALYs (11,546 person-years). The average relative age-standardized attributable burden was 314 DALYs per 100,000 person-years, highest at aged 75-80 years (1,407 DALYs per 100,000 person-years). As for the effect and correlation of GLP-1 RAs on glycemic and weight reduction, a total of 31 double-blind randomized controlled trials with 22,948 participants were included. The MD and 95% CI of the pooled GLP1-RA in the glycated hemoglobin level was -0.78 (-0.97, -0.60) % in the random-effects model and -0.45 (-0.47, -0.44) % in the fixed-effect model. The pooled body weight reduction was -4.05 (-5.02, -3.09) kg in the random-effects model and -2.04 (-2.16, -1.92) kg in the fixed-effect model. The standardized pooled correlation coefficient between HbA1c levels and body weight was -0.42. Finally, among the 552,485 cancer patients (mean age, 60.6 years; women, 47.7 %) during the median follow-up period of 4.1 years, 32,634 cases of CVD were identified. Compared with that noted in the non-cancer population, the fully adjusted HR with 95% CI was 1.28 (1.25, 1.30) in the cancer population. The CVD risk was the highest in the first year, the adjusted HR with 95% CI was 2.31 (2.23, 2.40), and this risk decreased yearly. Conclusion: A total of 18% of CVDs could be reduced in Taiwan if obesity/overweight was prevented. The absolute CVD burden from obesity/overweight was the highest in middle-aged men, and the relative burden was the highest in older adults. Resource allocation in targeted populations is required. Long-acting GLP-1 RAs significantly reduced the glycated hemoglobin level and body weight in adults. A negative correlation between glycemic control and weight reduction was obtained. Also, patients with cancer had a significantly higher risk of CVD. The risk was the highest in the first year since diagnosis and decreased yearly.