. 2022 Jul 4;11(13):e025973. doi: 10.1161/JAHA.122.025973

Table 2.

Summary of Key Observational Studies and Meta‐Analyses Published in 2021 That Address Primary Prevention of ASCVD or Treatment of an ASCVD Risk Factor

Study	Type of study	Study population	Intervention/study setting	Primary outcome	Secondary outcomes	Adverse outcomes
Obesity
Syn NL et al ²	Meta‐analysis	174 772 adults from 16 highly matched cohort studies and one clinical trial	Compared all‐cause mortality of adults with obesity who underwent metabolic–bariatric surgery compared with matched controls who received usual care	Metabolic–bariatric surgery associated with a reduction in hazard rate of death of 49.2% (95% CI 46.3–51.9, P<0.0001) Median life expectancy 6.1 y (95% CI 5.2–6.9) longer than usual care	Gain in median life expectancy among adults with T2DM was 9.3 y vs 5.1 y in adults without diabetes NNT to prevent one additional death over 10 y were 8.4 (95% CI 7.8–9.1) for adults with T2DM and 29.8 (21.2–56.8) for those without diabetes	NA
Cardiometabolic conditions
PESA (Progression of Early Subclinical Atherosclerosis) Study ⁶	Observational	3973 adults without diabetes, ages 40–54 y	Two‐dimensional ultrasound and non‐contrast cardiac CT used to detect subclinical atherosclerosis (SA) in carotid and femoral/iliac arteries, infrarenal aorta and coronary arteries	HbA1c showed an association with multiterritorial extent of SA OR 1.05 for HbA1c 4.9–5.0%, OR 1.27 for 5.1–5.2%, OR 1.27 for 5.3–5.4%, OR 1.36 for 5.5–5.6%, OR 1.8 for 5.7–5.8%, OR 1.87 for 5.9–6.0%, OR 2.47 for 6.1–6.4%, respectively; reference HbA1c 4.8%; P<0.001
Hypertension
Blood Pressure Lowering Treatment Trialists Collaboration ²³	Meta‐analysis	51 primary and secondary ASCVD prevention trials	Included RCTs of pharmacological BP‐lowering vs placebo or other classes of BP‐lowering medications, or between more vs less intensive treatment, with at least 1000 persons‐years of follow‐up compared effects of blood‐pressure‐lowering treatment on ASCVD risk stratified by age and blood pressure at baseline	HR for MACE per 5 mm Hg reduction in SBP for each age group: −0.82 (95% CI 0.76–0.88) in adults <55 y −0.91 (0.88–0.95) adults 55–64 y, −0.91 (0.88–0.95) adults 65–74 y, −0.91 (0.87–0.96) in those aged 75–84 y, and −0.99 (0.87–1.12) in those aged ≥85 y (adjusted P interaction=0.050)	NA	NA
Blood Pressure Lowering Treatment Trialists Collaboration ²⁴	Meta‐analysis	22 primary and secondary ASCVD prevention trials	Included RCTs in which specific class or classes of antihypertensive drugs vs placebo or other classes of blood pressure lowering medications that had at least 1000 persons‐years of follow‐up; studied association of blood pressure reduction with risk of incident T2DM; examined association of specific drug classes with risk of incident T2DM	SBP reduction by 5 mm Hg reduced risk of T2DM across all trials by 11% (hazard ratio 0.89 [95% CI 0.84–0.95]); ACEI (RR 0.84 [95% 0.76–0.93]) and ARBs (RR 0.84 [0.76–0.92]) reduced risk of new‐onset T2DM; β blockers (RR 1.48 [1.27–1.72]) and thiazide diuretics (RR 1.20 [1.07–1.35]) increased this risk, calcium channel blockers had not effect (RR 1.02 [0.92–1.13])	NA	NA
Polypill and fixed dose combination treatments
Polypill meta‐analysis ²⁸	Meta‐analysis	3 large RCT clinical outcomes trials of fixed‐dose combination vs placebo in primary prevention populations	TIPS‐3, HOPE‐3, PolyIran, n=18 162 participants; mean follow‐up 5 y	Composite of cardiovascular death, MI, stroke, or arterial revascularization 3.0% polypill vs 4.9% placebo (HR 0.62 [0.53–0.73]). Greater effects with ASA (HR 0.53 [0.41–0.67]) than without ASA (HR 0.68 [0.57–0.81])	Cardiovascular death (HR 0.65=[0.52–0.81]); MI (HR 0.52 [0.38–0.70]); stroke (HR 0.59 [0.45–0.78]); revascularization (HR 0.54 [0.36–0.80])	Dizziness 11.7% polypill vs 9.2% placebo, P<0.0001; GI bleeding 0.4% polypill with aspirin vs 0.2% combined placebo, P=0.15
Diet
Nurses' Health Study and the Health Professionals Follow‐up Study, plus additional cohorts ³⁵	Observational and meta‐analysis	66 719 women from the Nurses' Health Study (1984–2014) and 42 016 men from Health Professionals Follow‐up Study (1986–2014) who were free from CVD, cancer, and diabetes at baseline repeated analyses in meta‐analysis of 24 additional cohort studies	Examined association of fruit and vegetable intake and mortality	Compared with the reference level (2 servings/d), 5 servings of fruit and vegetables/day was associated with HR (95% CI) 0.87 (0.85–0.90) for total mortality, 0.88 (0.83–0.94) for CVD mortality, 0.90 (0.86–0.95) for cancer mortality, and 0.65 (0.59–0.72) for respiratory disease mortality	Dose–response meta‐analysis with 1 892 885 participants yielded similar results (summary risk ratio of mortality for 5 servings/d=0.87 [95% CI, 0.85–0.88]; Pnonlinear <0.001)	NA
UK Biobank ³⁶	Observational	422 791 participants with dietary data available	Compared incidence and mortality risk for CVD, ischaemic heart disease, MI, stroke, and HF among people with different types of diets—including vegetarians, fish eaters, fish and poultry eaters, and meat‐eaters	After a median follow‐up of 8.5 y, fish eaters, compared with meat‐eaters, had lower risks of incident CVD (HR): 0.93 (95% [CI]: 0.88–0.97), IHD (HR: 0.79 [95% CI: 0.70–0.88]), MI (HR: 0.70 [95% CI: 0.56–0.88]), stroke (HR: 0.79 [95% CI: 0.63–0.98]) and HF (HR: 0.78 [95% CI: 0.63–0.97]) Risk of adverse outcomes was not different in fish and poultry eaters compared with meat‐eaters
PURE (Prospective Urban Rural Epidemiology) cohort ³⁸	Observational	119 575 individuals ages 35–70 y living on 5 continents, from high, medium, and low‐income countries ages	Used country‐specific food‐frequency questionnaires to determine dietary intake and estimate glycemic index; examined the association of glycemic index with incident MACE (cardiovascular death, nonfatal MI, stroke, and HF) or death from any cause	A diet with a high glycemic index was associated with increased risk of MACE or death, both among participants with preexisting CVD (HR, 1.51; 95% CI, 1.25–1.82) and among those without CVD (HR, 1.21; 95% CI, 1.11–1.34)		NA
Framingham Offspring Study ³⁹	Observational	3003 adults free from CVD with valid dietary data at baseline	Data on diet, measured by food frequency questionnaire, anthropometric measures, and sociodemographic and lifestyle factors were collected quadrennially from 1991 to 2008 Examined association of consumption of ultra‐processed food and cardiovascular outcomes	On average, participants consumed 7.5 servings per day of ultra‐processed foods at baseline Each additional daily serving of ultra‐processed foods was associated with a 7% (95% CI: 1.03–1.12), 9% (95% CI: 1.04–1.15), 5% (95% CI: 1.02–1.08), and 9% (95% CI: 1.02–1.16) increase in risk of hard CVD, hard CHD, overall CVD, and CVD mortality, respectively		NA

ASCVD indicates atherosclerotic cardiovascular disease; CHD, coronary heart disease; CVD, cardiovascular disease; HR, hazard ratio; IHD, ischemic heart disease; MACE, major adverse cardiovascular events; NNT, number needed to treat; OR, odds ratio; RCT, randomized controlled trial; RR, relative risk; and T2DM, type 2 diabetes.